Jean-Louis Dessalles

GENERALISED SIGNALLING: A POSSIBLE SOLUTION TO THE PARADOX OF LANGUAGE

The systematic and universal communicative behaviour that drives human beings to give honest information to conspecifics during long-lasting conversational episodes still represents a Darwinian paradox. Attempts to solve it by comparing conversation with a mere reciprocal cooperative information exchange is at odds with the reality of spontaneous language use. The Costly Signalling Theory has recently attracted attention as a tentative explanation of the evolutionary stability of language. Unfortunately, it makes the wrong prediction that only elite individuals would talk. I show that as far as social bonding is assortative in our species, generalised signalling through language becomes a viable strategy to attract allies.

Introduction: coping with the evolutionary paradox

Language is an idiosyncratic property of the human species. Though, since the reasons for its very existence have been for long considered beyond question, the only remaining issues concerning its origin are to find out when, where and how it emerged in our lineage. Even recently, some authors insisted on the "obvious" necessity of language.

" It is possible to imagine a superintelligent species whose isolated members cleverly negotiated their environment without communicating with one another, but what a waste! There is a fantastic payoff in trading hard-won knowledge with kin and friends, and language is obviously a major means of doing so " (Pinker, 1994:367.) " The adaptive significance of human language is obvious. It pays to talk. Cooperation in hunting, making plans, coordinating activities, task sharing, social bonding, manipulation and deception all benefit from an increase in expressive power. " [START_REF] Nowak | Towards an evolutionary theory of language[END_REF] Unfortunately, there is no way to prove the existence of a general selection pressure towards language that only our lineage would have been responsive to. Moreover, no satisfactory explanation is currently available to account for the fact that individuals would find a selective advantage in giving away hard-won knowledge about their physical and social environment for free.

Traditional intuitions about evolution based on the species' welfare or on group selection have been dismissed for a long time [START_REF] Williams | Adaptation and natural selection: A critique of some current evolutionary thought[END_REF], and even if attempts have been made to revive them as potentially sound [START_REF] Sober | Unto Others. The Evolution and Psychology of Unselfish Behavior[END_REF], it remains highly unlikely that such mechanisms produce any selection pressure a (Williams, 1966:112). The only traditional alternative left to explain altruistic talking to unrelated conspecifics is reciprocal cooperation [START_REF] Trivers | The evolution of reciprocal altruism[END_REF][START_REF] Axelrod | The evolution of cooperation[END_REF]. The conditions for the stable existence of cooperation are well known [START_REF] Dessalles | Coalition factor in the evolution of non-kin altruism[END_REF]: good benefit-to-cost ratio and good cheater detection. Spontaneous language is far from meeting those requirements. The informational content of most everyday chatter is unlikely to significantly change the hearers' life expectancy, and the cost of talking should not be underestimated, if only for the time devoted to it [START_REF] Dunbar | Theory of mind and the evolution of language[END_REF]. But the second constraint is even more patently infringed. Cheating, in the case of language, means that the addressee takes the information given and does not give information in return, even with delay. At first sight, the dialogic nature of many conversations seems to support the cooperative view. A closer examination of spontaneous exchanges reveals a Elementary calculus shows that behaviour in favour of the collective with no return for the individual may have a slight positive effect on the frequency of that behaviour, but this effect requires strong heterogeneity and low migration within the population; it is frequency-dependent and vanishes when the behaviour becomes predominant; it presupposes the absence of any alternative behaviour that would be selfish and profitable. Simulations show that the effect does not emerge from noise and that it disappears when individuals endure event small costs. Dessalles, J-L. (2006). "Generalised signalling: a possible solution to the paradox of language". In: A. Cangelosi, A. D. M. Smith & K. Smith (Eds),

The evolution of language. Singapore: World Scientific, 75-82.

a quite different picture. To avoid cheating, speakers should rely on good assessment and memory of who gave valuable information to whom. Such bookkeeping is compatible with conspiratorial whispering, not with open conversation. Observation of spontaneous exchanges reveals that speakers talk to more than two addressees on average [START_REF] Dunbar | Size and structure of freely forming conversational groups[END_REF]. If reciprocation were the underlying mechanism of language, talkative behaviour would have been selected against. There are more loquacious individuals around who are in search of an audience than people withholding valuable information and waiting for being prompted by avid hearers. Moreover, cheating detection seems to be performed by hearers rather than by speakers, as the former systematically point to any inconsistencies they perceive in what they hear [START_REF] Dessalles | Altruism, status, and the origin of relevance[END_REF]. Conversation is more like scientific communication, in which authors strive to make a point that will be critically appraised by their colleagues, rather than like communication among spies or speculators, where information is exchanged on a strictly reciprocal basis. b

Costly signalling and human language

A new paradigm to explain non-kin altruism recently emerged from the pioneering work of Amotz Zahavi [START_REF] Zahavi | The handicap principle[END_REF]. Altruistic behaviour may be performed in the absence of any reciprocation as a way to gain prestige in the group. The main claim of the theory is that these conducts evolved to advertise some quality. Another aspect of the theory is that competition leads to costly performance, as the handicap of the cost makes the performance a reliable indicator of the corresponding quality.

" […] my suggestion that altruism is an investment in advertisement by the individual altruist (that is, a handicap) shows how altruism can provide a direct benefit to the altruist. The individuals that accord prestige to the altruist do so not to encourage altruism, [… they] benefit directly from the information advertised by the altruistic act in their own decision making. " [START_REF] Zahavi | Indirect selection and individual selection in sociobiology[END_REF] This model has been shown to be theoretically consistent [START_REF] Grafen | Biological signals as handicaps[END_REF][START_REF] Gintis | Costly Signaling and Cooperation[END_REF]. As stated in Zahavi's quotation, one crucial requirement is that the individuals that witness the performance benefit from making a good appraisal and reward good performers. The two sides of this requirement may be simultaneously fulfilled if the former make an asymmetrical alliance with the latter, e.g. becoming their disciples or conversely accepting them as coalition mates. In Gintis et al. model (2001), performers benefit from being chosen and discerning coalition partners benefit from choosing high quality performers.

We may say of those models that they are political, as they deal with fruitful alliances among individuals. The main reason for individuals to engage into coalition formation is that other individuals do so, what may create contexts in which isolated individuals are almost certain to lose. The crucial task each individual has to perform is to choose the best available allies, judging from available clues. As the individuals' true qualities are not directly observable, the selection task must rely on signals displayed by performers, as long as those signals are reliable. What [START_REF] Gintis | Costly Signaling and Cooperation[END_REF] showed is that conditions do exist in which honest signalling is stable and provides a true indication of the individuals' quality. Though, realistic conditions that meet the model's requirements are still to be discovered.

Transposing Costly Signalling Theory (CST) to human language is not straightforward. Talking would be a way of advertising some crucial quality for forming efficient coalitions. Several problems must be solved: (1) Which quality is advertised through linguistic performance? (2) Is that quality positively correlated with the success of coalitions? (3) How is the reliability of signals enforced? (4) Why is language a generalised behaviour, while CST predicts that only high quality individuals should show off?

In previous work, we attempted to answer problems (1)-(3) [START_REF] Dessalles | Altruism, status, and the origin of relevance[END_REF](Dessalles , 2000a(Dessalles , 2000b)). ( 1) By striving to make relevant utterances, individuals would demonstrate their ability to extract information from their physical and social environment. Spontaneous conversations constitute an arena in which individuals compete to show that they were first to detect unexpected events that, without them, may have passed b Cooperation can be made more robust by introducing intense punishment, but punishment exerted by speakers is absent from spontaneous language. Correlations between players are also known to stabilise cooperation, but they amount to introducing some dose of kin selection into the system. Human language is spontaneously used without specific and obligatory consideration of genetic, spatial or aspect closeness.

unnoticed.

(2) This informational ability is supposed to be a useful quality for large coalitions. When five coalition mates or more are to take coordinated action, the presence among them of individuals who are fully in touch with the physical and social environment is a crucial asset. Conversely, the coalition is unlikely to perform well if none of its members knows about what is going on around. Through language, individuals continuously demonstrate their ability to extract relevant information from their surroundings or from their past experience. Even if the recounted events are most often futile, it is still a good way to show off as a valuable coalition mate.

(3) In CST, reliability is guaranteed by the cost of the performance. However, as Zahavi observes (Zahavi & Zahavi 1997:223), it is easy to lie with words. If performance is appraised according to the informational unexpectedness or importance of the reported events, it is tempting to report highly unlikely events by merely inventing incredible situations and pretending to have witnessed them. We proposed that logic and argumentation evolved as a way to deter liars [START_REF] Dessalles | Altruism, status, and the origin of relevance[END_REF], and that language may be honest in the absence of direct cost, as it is difficult to lie while remaining logically consistent. Problem (4) remains a difficulty. In CST, signalling is honest as far as it allows telling apart high quality from low quality individuals. In an open and reliable competition, low quality individuals have no interest in showing off, as their performance would precisely reveal that their quality is low. How can we explain that language is a generalised behaviour in our species? CST would let us expect that only individuals capable of announcing big scoops or of making the soundest discussions would dare to talk. This is obviously not the case.

The problem of the signalling threshold

CST predicts a sharp cut-off in the level of signalling. Above a definite quality value, signalling becomes profitable, even if it is costly and altruistic, as the "political" return in terms of making efficient alliances compensates for the cost. Below that quality threshold, the probability of being chosen as coalition mate becomes too low and no longer compensates for the immediate cost. In previous unpublished attempts, we tried to circumvent the difficulty by adding noise and uncertainty both in the production of signals and in the formation of alliances. Though the consequence was an actual lowering of the signalling threshold, these efforts proved unsatisfactory. When signals become less correlated with the quality in demand, "customers" turn away from them even if communication is honest [START_REF] Izquierdo | Market failure caused by quality uncertainty[END_REF]. Moreover, as CST shows, good quality signallers evolve to reveal their higher quality anyway, most often by enduring high costs that lower quality individuals cannot afford.

In the case of language, even if logical testing by listeners can ensure reliability in the absence of significant marginal cost, the signalling threshold problem remains intact: we would expect that the only individuals talking in conversation would be those who were able to gather genuine extraordinary or crucial experience, while it would be advantageous for those who have only banal events to report to remain silent. Human verbal interactions would look be quite different from what they are, something like alarm calls that occur infrequently. c The thesis of this paper is that the existence of language, as it is practised hours each day by virtually all healthy individuals in traditional societies [START_REF] Dunbar | Theory of mind and the evolution of language[END_REF], can be explained within the CST framework under the assumption that social bonding is assortative.

Language and assortative social bonding

One crucial characteristic of human social behaviour is that it produces assortative matching. Even if you cannot become acquainted with prominent individuals many would dream of (for some it may be a famous actor, a politician, an important scientist or that person next door who ignores you), you still find some interest, and presumably some biological advantage, in establishing friendship bonds with people more like you. The point is that assortative matching gives a chance to everyone to be chosen, and so everyone benefits from displaying her/his quality.

The crucial parameter is the difference between the maximal number of links coming to a node and the maximal number of links going out of a node in the graph of social bonds. If the former is much higher, as when many people admire an opera singer, the competition generates an elite. Don't attempt to sing opera in public if you have a faint voice. Human friendship functions differently. The maximal number of friendship bonds an individual is able to establish corresponds roughly to the number of different friendship bonds individuals would accept. A consequence is that, at equilibrium, friendship bonds are assortative, i.e. they bind individuals of comparable "quality" (for whatever relevant quality considered). Fig. 1 shows how pairings may stabilize to be roughly assortative during a computer simulation, as individuals of various qualities (on the horizontal axis, below) tend to bind with individuals of comparable quality (on the horizontal axis, above). The left part of the figure was obtained by imposing one-to-one pairings. The right part of the figure shows a case of non-assortative pairing. The political advantage for an agent of attracting allies may be written f(q+Q), where q is the quality of the individual, Q the quality of the support provided by its allies,  is a constant and f() an increasing function. In this simple model, individuals may reveal their quality by emitting a signal s=gq that depends on their quality and on a genetically coded value g. Producing the signal involves the cost Cg, where C is a constant. Finally, the quality of the recruited allies, and thus their support, depends on s: Q=h(s), where h() is an increasing function. The benefit for the signalling individual is: f(q+h(gq))-Cg. At equilibrium, its first derivative in g is zero, and thus: qh'(gq) f '(q+h(gq))=C, which gives the optimal value of g to which evolution will lead. h'(s) represents the marginal increase of the recruitment level. In the case of nonassortative paring, h'() is zero or negligible below a threshold value of the signal, where it takes high values. As a consequence, if f () does not change value abruptly, the equation has no solution in g for small values of q and non-negligible cost C. This is the standard result of CST. In assortative pairing, h() is expected to increase smoothly, as slightly better signals attract slightly better friends. h'(s) is thus non-zero and the equation may have a solution for any value of q, which means that signalling is now generalised.

Computer simulations confirm this result. Plots on Fig. 2 show how much individuals invest in communication, depending on their quality: low (black), medium low (white), medium high (red) and high (blue). The two first plots (left and middle) were obtained for two different benefit functions f(). The plot in the middle shows that there are conditions in which, though communication remains honest, it is more profitable for low quality individuals to invest more in communication than higher quality individuals. The plot on the right corresponds to non-assortative links. It shows a typical CST result where only high quality individual are signalling.

Conclusion

The main point of this paper was to show that generalised signalling is possible within the framework of CST thanks to assortative social bonding, and that the existence of language could be a consequence of this phenomenon. The crucial difference with various forms of kin-based cooperation, in which individuals are bound to interact with resembling or proximal partners, is that coalition mates choose each other. The fundamental hypothesis is that language controls social bonds, while actual bonds are not a prerequisite for the former to exist.

Several points must be more precisely investigated. For instance, several aspects of the social game, such as the selection of best partners by displaying individuals, are merely enforced in the simulation, instead of being left to emerge. We think nevertheless that this simple experimental setting offers new support to the idea that human language emerged as a signalling device to advertise information abilities.

Figure 1 .

 1 Figure 1. Examples of assortative (left) and non-assortative (right) pairings.

Figure 2 .

 2 Figure 2. Three examples of evolution of investment in communication depending on quality.

c In some forms of signalling, the threshold may be close to zero, as is possibly the case for costly sexual mating in some singing bird species. If this is the case, it is due to the fact that males have no alternative than song to have the slightest chance for mating. This situation does not obtain in human coalition formation, as a variety of qualities such as fidelity, courage, efficiency or actual social status offer alternatives to informational abilities for showing off.


Jean-Louis Dessalles
email: dessalles@enst.fr-

From protolanguage to language: model of a transition

Keywords: semantics, syntax, evolution, recursion, cognition 1. Introduction: Anatomy of a transition 1

The existence of syntactic abilities allowing human beings to process complex languages remains mysterious. According to some authors, these abilities appeared by mere chance at some point in evolution, and their use in communication is, in some way, fortuitous. We try here to show how a simple model of the syntaxsemantic interface allows us to consider a quite different scenario. The ability to process syntactic structures would have appeared in a two-step evolutionary process and would be the consequence of a new semantic ability, the ability to form predicates. Recursion is claimed to have appeared in the second step, as a way to link predicates for their arguments to be determined.

Human language behaviour relies on various cognitive abilities that are peculiar to our species. Animal communication systems qualitatively differ from ours. Attempts to teach apes various aspects of human language [START_REF] Premack | L'esprit de Sarah[END_REF][START_REF] Savage-Rumbaugh | Kanzi: the ape at the brink of the human mind[END_REF][START_REF] Pepperberg | The Alex studies -Cognitive and communicative abilities of grey parrots[END_REF]) reveal that various cognitive abilities that allow us to process language seem to be absent from the tested species. One of these abilities that is often mentioned is the use of syntax. It is true that birds, nightingales for instance, are known to emit songs with several combinatorial layers (Hauser 1996:286). However, nothing indicates that the various structures they utter express differentiated meanings. Trained primates sometimes spontaneously produce utterances involving two words that are semantically related to the concrete intended meaning, with some tendency to observe a systematic order (Savage-Rumbaugh & Lewin 1994 :161). This type of performance however remains quite far away from human linguistic productions, what leads some authors to see there rather the expression of a protolinguistic ability [START_REF] Bickerton | Language and species[END_REF]1995).

Protolanguage was defined, extrapolating from pidgins, as a form of expression in which words are merely grouped in short utterances, with no grammatical support. Its characteristics are: no grammatical words, no long-range dependency within the sentence, no inflection, no _______ 1 This study was conducted thanks to the CNRS-OHLL initiative (Origine de l'Homme, du Langage et des Langues). consistent order [START_REF] Bickerton | Language and species[END_REF]. Protolanguage is what we settle for when we are in linguistic trouble. Bickerton presents it as a precursor of language, an intermediary competence between spontaneous primate communication and language proper, which is universally used in our species. A modern expression of protolanguage can be observed in the use of search engines on the World Wide Web. Though these search engines recognise Boolean expressions and possibly noun phrases, users tend to input sequences of grammatically unrelated words [START_REF] Guichard | L'internet : mesures des appropriations d'une technique intellectuelle[END_REF].

Whatever the status we grant to the protolanguage hypothesis, the issue of the evolutionary transition to language as we know it cannot be ignored. Some cognitive abilities enable us to process meaningful linguistic structures and to perform non trivial operations on these structures, as questioning, passive voice, modal or temporal modifications, and so on. Without deciding here whether these cognitive abilities are specific to language or depend on more general dispositions [START_REF] Piattelli-Palmarini | Théories du langage -Théories de l'apprentissage[END_REF], we are looking in the structure of language some clues that may reveal their order of appearance. In this attempt to reconstruct the phylogeny of this transition to language, we will specifically concentrate on the interface between syntax and semantics, from a modelling perspective. By examining the relative complexity of synchronising operations between syntactic structure and meaning, we will be able to propose an order of appearance for some of the abilities that underlie language competence.

In what follows, we will first set the problem by considering some characteristics of syntax that are generally invoked to demonstrate the originality of our communication mode, such as recursion and inflection systems. We will outline a simplified model of the role these characteristics play in the expression of meaning. From this simplified model, we will draw some propositions concerning a plausible sequence in the establishment of the cognitive abilities that underlie these language properties. We will conclude by replacing these propositions in the broader framework of current research on the evolutionary origin the language faculty.

Some significant aspects of the syntactic faculty

Languages are highly varied, but not indefinitely so. In particular, all spontaneous languages in the world, with the exception of recent pidgins, involve grammars that rule the flexion of words and their relative position in the sentence. No people in the world spontaneously speaks by grouping invariable words with no consistent order.

1 It is true that syntactic rules highly differ from one language to the next. Some languages like Latin of Dyirbal seem quite permissive about word ordering in simple clauses [START_REF] Dixon | The Dyirbal language of North Queensland[END_REF], whereas other languages like French or English are significantly less tolerant on this aspect of grammar. Other languages like Lakhota involve a complex morphological system that mainly affects the verb, while languages like English or Chinese are use inflection quite sparingly [START_REF] Van Valin | Syntax. Structure, meaning and function[END_REF]. Despite these obvious differences, some general observations can be made concerning the common structure of languages that will be sufficient to support the remainder of our claim.

The first obervation concerns the existence of dependencies between words. In a protolinguistic utterance like house-neighbour-fire, each of the three words bears a direct semantic relation with the perceived scene that is described. Communication can function with such utterances without words being dependent on each other. Human languages involve several forms of dependence that are clearly indicated by grammar. In a sentence like the neighbour's house is on fire, words bear formal relations that are independent of their meaning. For instance, words like on and fire are tied together by some relation, as are house _______ 1 Recently created pidgins clearly constitute an exception. However, they are used as main language only under abnormal social conditions in which adult individuals from different linguistic communities are brought together [START_REF] Bickerton | Language and species[END_REF]). The history of creoles and the recent example of deaf signing children in Nicaragua [START_REF] Kegl | Creation through Contact: Sign Language Emergence and Sign Language Change in Nicaragua[END_REF] suggest that pidgins are instable communication forms that disappear as main communication means when the social structure allows children under seven to form communities. and neighbour, while neighbour and fire are not directly linked. These dependencies most often prevail over meaning: the grammar of a sentence like the mouse eats the cat impose a semantic relation that goes against what is suggested by the mere association between the meanings evoked by the words mouse, cat, eat.

The second observation concerns the fact that grammatical dependencies are asymmetrical. In a Latin expression like domus domini, the genitive of the word dominus unambiguously indicates that the word is a satellite of the word domus. In French, the two expressions la maison du maître et le maître de la maison can be distinguished by the relative position of the words with respect to preposition de. This asymmetrical dependency can be interpreted in various ways, either as resulting from a syntactic merging operation [START_REF] Chomsky | The minimalist program[END_REF] or as a semantic dependency [START_REF] Van Valin | Syntax. Structure, meaning and function[END_REF]. Thanks to asymmetrical dependencies, linguistic utterances involve phrases in which the head is, in a structural sense, above the dependent elements.

The third observation concerns the "molecular" structure of linguistic utterances. As dependencies can branch on each other, phrases end up embedded into each other. In a simple sentence like I fairly liked the subject of the conference we attended yesterday, several embeddings are to be observed: the verb phrase headed by the verb attend depends on the noun phrase headed by conference; the latter is an integral part of the noun phrase headed by subject, which is included in the phrase headed by liked. Different syntactic theories may differ by the precise choice of phrase types, but all acknowledge the embedding principle. The resulting structures can be said to be tree-like (if one represents the graph of dependencies), molecular (by analogy with biochemistry in which macro-molecules are composed of other molecules), fractal (in reference to living or physical structures that are scale-invariant) or recursive. This last qualifier refers to a property of the procedure that allows to read or to generate the syntactic structure. Recursive procedures have the property of calling copies of themselves during their execution. The same procedure is used to analyse the noun phrase subject of the conference we attended yesterday and the embedded noun phrase conference we attended yesterday. From a technical point of view, the remarkable fact is that the recursion at work in human language is a central recursion that cannot be reduced to a mere repetitive iteration.

Our last observation concerning syntactic dependencies is that they have long distance effects. In: the subject of the conference we were lucky enough to attend yesterday, the noun conference acts as a complement both of subject and of attend, despite the fact that the latter and conference are separated by five words. The distance in this kind of dependency can grow arbitrarily (the conference that the friend who was my roommate before I moved to Paris was lucky enough to attend yesterday was on a scandalous topic). Syntactic theories may give different accounts of these long range dependencies, depending on whether they consider movement (the complement of attend would migrate toward the head of the main clause) or silent duplication.

For several authors, some of the above mentioned syntactic properties are inseparable. The existence of asymmetrical dependencies, phrase embedding and the various forms of long range dependencies would go together; they would constitute a package that Nature would have offered us together with syntactic competence. This set of properties would be the automatic result of the sole "merge" operator [START_REF] Berwick | Language evolution and the minimalist program: the origin of syntax[END_REF] or, equivalently, of the fortuitous appearance in our species of the ability to process recursive structures [START_REF] Hauser | The faculty of language: what is it, wo has it, and how did it evolve ?[END_REF]. Indeed, it is difficult to imagine intermediary steps in the mastery of recursion. It seems, therefore, that the transition from protolanguage (or from non-language) to language can only be a sudden one. Some have invoked the possibility of an improbable macromutation [START_REF] Bickerton | Language and species[END_REF]. Its cause could have been fully fortuitous, and it would owe nothing to any increase in communication power (Chomsky 1975 :75 ;[START_REF] Piattelli-Palmarini | Evolution, selection and cognition: From 'learning' to parameter setting in biology and in the study of language[END_REF]Lightfoot 2000). The new recursive ability, possibly thanks to the break of some functional encapsulation [START_REF] Hauser | The faculty of language: what is it, wo has it, and how did it evolve ?[END_REF], would have produced the whole set of syntactic properties that are to be observed in the various languages, including the dependency properties that we mentioned above.

The evolutionary transition toward syntactic competence looses much of its scientific interest if it is supposed to have been sudden and fortuitous, as it was likely to produce a device that is poorly adapted to the communicational needs of humans.

Language design as such appears to be in many respects "dysfunctional," yielding properties that are not well adapted to the function language is called upon to perform. (Chomsky, 1995:162).

[…] full-blown evolutionary novelty can also suddenly arise, so to speak, for no reason, because novelty caused by sheer proximity between genes is not governed by function and it, therefore, eludes strict adaptationism. » (Piattelli-Palmarini 1989:8)

The thesis according to which evolution would produce complex and poorly functional structures or competences is at odds with biological laws [START_REF] Dessalles | L'ordinateur génétique[END_REF] and do certainly not apply to language [START_REF] Pinker | Natural language and natural selection[END_REF][START_REF] Pinker | The faculty of language: what's special about it?[END_REF]. Both the theory of evolution through natural selection and the study of language suggest that syntax fulfils a definite function, which is to serve the expression of meaning on the vocal-auditory channel, and that its structure is an evolutionary consequence of this function. It is thus legitimate to wonder which function is carried out by syntax, and especially recursion, and then to propose a tentative reconstruction of the main steps through which the evolution of language may have gone.

In what follows, we will question these two alleged properties of the transition from protolanguage to language, namely its abrupt and its fortuitous character. By observing, from a modelling perspective, the interface between syntax and semantics, we will suggest a at least two-step transition, each step being motivated, on the biological ground, by its consequences on the new types of communication it makes possible.

At the interface between grammar and meaning

The way an utterance is built up from its grammatical structure has been thoroughly studied and is still the subject of many studies. Paradigms differ largely, ranging from isomorphic constructions [START_REF] Montague | Formal Philosophy[END_REF][START_REF] Jackendoff | Semantic structures[END_REF][START_REF] Carpenter | Type-logical semantics[END_REF] to various conceptions in which grammatical structure only imposes constraints to a semantic process running in parallel [START_REF] Johnson-Laird | Procedural semantics[END_REF][START_REF] Kamp | From discourse to logic : Introduction to modeltheoretic semantics of natural language, formal logic and Discourse Representation Theory[END_REF][START_REF] Talmy | Toward a Cognitive Semantics: Concept Structuring Systems[END_REF]. For our purposes here, a global theory of meaning construction is not necessary. We just need to consider some aspects of the synchronisation between the syntactic code and the semantic level.

The first aspect of this synchronisation concerns the recognition of the predicate-argument relation. We consider the simplifying hypothesis that the semantic representation of a given utterance involves a logical predicate.

1 This hypothesis is compatible with most models of semantics.

2 It is important to note that this hypothesis does not require the existence of a language of thought, as the predicate in question can be a transitory representation that is constructed on the fly from non symbolic elements [START_REF] Ghadakpour | Le système conceptuel, à l'interface entre le langage[END_REF].

Let us take the example of a two-place predicate P(x,y), such as the predicate associated with the sentence Pierre hits Paul. One of the fundamental functions of syntax is to offer means to locate x, y and P in the sentence. In particular, it makes the distinction between the sentences corresponding to P(x,y) and P(y,x). Languages make use of various means to achieve this identification of participant roles. The most obvious are position and inflection. In a language like English, the relative location of words is strict enough for listeners to locate the predicate and its arguments, and to distinguish the meanings of Pierre hits Paul and Paul hits Pierre. In Latin, the nominative and accusative cases fulfil the same function in a sentence like Paulus Petrum ferit. The grammar of a given language also give means to locate predicates _______ 1 Logical predicates are the easiest way to interface meaning with pragmatic aspects, especially argumentation [START_REF] Dessalles | Aux origines du langage : Une histoire naturelle de la parole[END_REF].

2 In particular, one can convert into logical predicates all constructs hypothesised in models based on feature structures, on logical or functional formalisms, on graphs or on schematic representations. Models that only consider analogue meaning representations, such as images, could constitute an exception.

and arguments in the case three-place predicates (Paul sells his car to Jacques), one-place predicates (Paul is sick) or zero-place predicates (it rains).

In the preceding section, we presented the existence of asymmetrical dependencies within the phrase as a fundamental characteristic of language. One of its effects is precisely to make the identification of the relation between the predicate and its arguments possible. In other words, phrases are the visible counterpart of predication. Let us call argumental function this property of syntax.

The second aspect of the synchronisation between syntax and semantics that we will consider is determination. To be of any use at the pragmatic level, the semantic representation must be sufficiently instantiated. In some contexts, it is not the fact that whatever living being ate something that matters, but rather the fact that the house cat ate the joint of roast beef that I intended to our guests. In another context, for instance the case of a sick person recovering her appetite, the identity of the eater is relevant, whereas the eaten entity may remain unspoken. Let us see how syntax fulfils the function of determining the arguments of predicates.

There is a variety of means through which syntax performs the determination of arguments. Let us concentrate on two of them, modification and relative clauses. In the following sentence:

Go and fetch the small book that Paul offered to Jacques the modification of book by the adjective small and the relative clause that Paul offered to Jacques helps the listener understand which book the demand is about. If one represents the corresponding meaning with predicates, one gets a representation like Small(x) & Book(x) & Offer(Paul,x,Jacques), under the assumption that the listener is able to form, in the current context, the predicates noted Small, Book and Offer. In this type of representation (which reminds the computer programming language Prolog), the convention is that two variables of same name, within the same logical clause, designate the same object. One could think of human beings expressing that way, with simple clauses and variables: Go and fetch something; That something is a book; That something is small; Paul offered that something to Jacques. This expression mode, based on variable sharing between simple propositions, appears rather clumsy to most of us (though a minority of computer scientists really like using it to express precise knowledge in Prolog). Thanks to the syntax of natural languages, the use of explicit variables proves unnecessary, as illustrated in the following schema.

In this schema, arrows stand for the semantic link that exists between phrases. This semantic link results from various syntactic devices. One of them, the principle of semantic linking, states that two phrases that bear a syntactic relation (complementation or adjunction) must share a variable at the semantic level 1 [START_REF] Dessalles | Aux origines du langage : Une histoire naturelle de la parole[END_REF]. This principle corresponds to _______ 1 This principle must be applied with some caution. For instance, it requires distinguishing the predicative sense of a preposition like on (as in she saws the book on the table) from the non predicative sense (as in she relies on Paul). In the latter case, there is only one predicate and thus no semantic linking.

F e t c h ( J e a n , _ ) B o o k ( _ ) S m a l l ( _ ) O f f e r ( P a u l , _ , J a c q u e s )

the linking of discourse fragments that is hypothesised in a formalism like DRT [START_REF] Kamp | From discourse to logic : Introduction to modeltheoretic semantics of natural language, formal logic and Discourse Representation Theory[END_REF]. The principle of semantic linking is not an infallible way of establishing the link between logical arguments. In English, a phrase like the overtaking of the car is ambiguous, as one cannot know whether the car in question is overtaking or is overtaken. The ambiguity is explained by the fact that the principle of semantic linking underspecifies, in this case, the shared argument in Overtake(_,_) & Car(_), where each of the two arguments of Overtake can be linked to Car.

The essential function of the principle of semantic linking and of the various syntactic devices that implement it is to allow for the determination of the objects of discourse. If one sees each of the predicates as a constraint laid by the speaker on the perceived world, each link with a new predicate restricts the range of possibilities, and thus facilitates understanding on the listener's side. Identify what the discourse is about consists in solving equations like Small(x) & Book(x) & Offer(Paul,x,Jacques), where x is the unknown. A relevant speaker will take care of giving sufficient predicative constraints for the solution to appear unique in the eye of listeners (the use of a definite determiner like the announces this uniqueness to them). In an already constrained context, merely expressing Book(x) may suffice. The principle of semantic linking makes the role of syntactic recursion clearer: Each new predicate that is introduced to specify the argument of another predicate can necessitate the introduction of further predicates to instantiate its own arguments. The result is a tree-like structure that links predicates together.

The principle of semantic linking acts locally on predicates that are close: complements or adjuncts. Paradoxically, the same principle of semantic linking accounts for some long range dependencies. In particular, it gives a role to movement (or silent duplication) of noun phrases, when two phrases must be connected despite their structural distance. In the phrase: the subject of the conference [that] we were lucky enough to attend yesterday, the problem is to link the arguments of Subject(_), of Conference(_) and of Attend(_,_). The word conference cannot be simultaneously the complement of the noun subject and of the verb attend. The optional pronoun that refers to the silent complement of attend and implements this double link. The principle of semantic linking operates between subject and its complement conference, and between conference and the optional pronoun that.

1 Semantic linking is also transmitted between that and the silent complement of attend. If our example is classically analysed as resulting from the complement of attend having moved towards the top of the clause, then the function of that movement is to bring conference to a position where it can link with subject.

We just mentioned two important functions of syntax, the argumental function and its role in determination. In a scenario in which the ability to process syntactic relations would be a pure result of chance, brought in for no reason into the human cognitive landscape, the very existence of these two functions and the fact that syntax makes a rather good job in fulfilling them looks rather miraculous. We suggest to reverse the picture and to see the ability to process syntax, not as a wondrous event devoid of any cause, but as the result of a multi-step evolution.

From modelling to the reconstruction of evolution

From a modelling perspective, syntax looks like a rather well-designed device that achieves at least two essential functions, the identification of predicate arguments and the determination of discourse objects through semantic linking between phrases. Understandably, we may go beyond these observations and investigate what the phylogeny of this device may have been. If one accepts to see in syntactic competence something else than a cognitive ability cast in one piece, given as a turnkey device thanks some evolutionary luck, then it is _______ 1 The status of this link between the relative pronoun that and its antecedent may vary according to the linguistic theory. We just need to say that semantic linking goes through it, event when the pronoun remains silent.

relevant to wonder about the order in which the various components of this capacity have appeared during the phylogeny of the species.

The reasoning is similar to what scientists studying anatomic evolution typically do. They draw a distinction between ancestral and derived characters. Whenever some morphological feature cannot exist in the absence of some other morphological character, it is necessarily derived. The ocellus that can be seen on some butterfly wings are derived characters that appeared after wings in the course of evolution. In the case of syntactic processing, it is relevant to wonder which, of the two functions that we considered, came first.

When asked this way, the question receives an unambiguous answer. Identifying predicates arguments is unquestionably a prerequisite of the possibility of performing semantic linking between predicates. In other words, the mastery of the syntactic tools that allow us to identify arguments must have been present before the ability to use semantic linking for determination.

The most important consequence is that the ability to process syntactic relations must have emerged in two steps, with recursion coming into play only in the second step. The scenario is the following one. First step: emergence of the ability to handle simple clauses that express only one predication. This predication can be said to be the main one: it is used at the pragmatic level for argumentation [START_REF] Dessalles | Aux origines du langage : Une histoire naturelle de la parole[END_REF]. The utterance Pierre hit Paul is directly exploitable by the listener, who can adopt a conversational attitude or even engage in some action. At this stage, predication is explicit in language, whereas it was absent from protolanguage (in a protosentence like fight-Pierre-Paul, where the three words come up to be together only because they relate to the same scene, the make up of a possible predication is the entire responsibility of listeners, who must in addition guess who is the hitter and who is the hittee).

In a second step, the ability to express predicates came to acquire a derived function. At that stage, utterances still include a main predication, which is the one that is used at the argumentative level. However, they now include auxiliary predications that are here for determination purposes. These secondary predications are expressed through modification by complementation or adjunction. Thanks to the principle of semantic linking, auxiliary predications can play the role of specifying the objects of discourse.

1 The remarkable phenomenon is that argument specification does not concern only the main predication, but also the secondary ones, as their arguments require specification as well. What results is a recursive linking of auxiliary predications which, thanks to the principle of semantic linking, can link to each other. It is thus at this point that the ability to process recursive phrase structures found its raison d'être.

Discussion

The main interest of the scenario that we just sketched is to make the unlikely hypothesis of a turnkey syntactic ability, appearing by chance to find a subsequent function in communication, dispensable. By taking the syntax-semantics synchronisation into account, we could distinguish two fundamental syntactic abilities that emerged successively, each one being motivated by a functional role. The first one made the expression of the main predication possible, by using simple isolated clauses for each predication. No need to invoke any miraculous event here. Various experiments in evolutionary simulations have shown that this form of syntax could emerge in a context where it is advantageous to express predications [START_REF] Batali | Artificial Evolution of Syntactic Aptitude[END_REF][START_REF] Batali | Computational simulations of the emergence of grammar[END_REF][START_REF] Kirby | Learning, bottlenecks and the evolution of recursive syntax[END_REF]. The role of syntax, in this case, is to provide visible marks of asymmetrical dependencies between the predicate and its arguments. The various inflection systems (case marking, gender, classes …) are in competition with word position to fulfil this _______ 1 In a marginal way, auxiliary predications can play an argumentative role. In: I saw the beautiful Mary who was in a hurry, the predications introduced by the adjective beautiful and by the relative clause who was in a hurry are not used to specify the objects of discourse, but express pieces of knowledge for argumentative purposes. In our scenario, these predicative use of auxiliary predications is, itself, derived from the their use in determination. function [START_REF] Jackendoff | Possible stages in the evolution of the language capacity[END_REF]2002). If there are two competing devices for the same function, fulfilling it cannot be a miracle, contrary to what the above mentioned authors seem to suppose (cf. section 2).

What prompts some authors to think that the mastery of syntax results from a unique and unlikely innovation is due to the molecular nature of linguistic utterances. The ability to embed phrases into each other, in a recursive way, cannot seem to be acquired in a progressive manner. In our scenario, this ability emerges in the second step, when auxiliary predications are used as determination constraints. We do not know if the emergence of recursive syntax is especially improbable when the problem is to express secondary predications that are semantically linked. There are, however, two indications that limit that improbability. First, some studies showed that recursive syntax could emerge in other contexts, to solve a problem of lexical economy [START_REF] Nowak | The evolution of syntactic communication[END_REF] or of semantic generalisation [START_REF] Kirby | Learning, bottlenecks and the evolution of recursive syntax[END_REF]. Second, recursive syntax is not the only way to express secondary predicate links. One can easily think of a way of expressing these links based on variable sharing, as in Prolog (cf. section 3). If such a device did not emerge to serve spontaneous human expression, it is probably because the principle of semantic linking emerged more rapidly, giving utterances a molecular structure and long range dependencies. Some studies present syntax as an innovation whose purpose was to solve the problem of heavy lexical pressure. Facing the increasing number of meanings to be communicated, syntactic combination appears as a way to limit the number of lexical forms that must be memorised (Kirby 2000;[START_REF] Nowak | The evolution of syntactic communication[END_REF]. From what precedes, one can understand that lexical pressure justifies, at best, the emergence of protolanguage. Protolanguage utterances, by combining meanings of juxtaposed words, can evoke scenes for which speakers have no unique adequate words [START_REF] Dessalles | Aux origines du langage : Une histoire naturelle de la parole[END_REF]. Syntax achieves a quite different job. It allows to express predication. According to our scenario, protolanguage was bound to the evocation of concrete scenes. The transition from protolanguage to language constituted a genuine innovation, though which our ancestors, by accessing to predication, engaged in the path to argumentation [START_REF] Dessalles | Aux origines du langage : Une histoire naturelle de la parole[END_REF].

The semantic capacity of predication has often been reduced to the activity of categorisation, which requires establishing a relation between a located object and a set of properties [START_REF] Hurford | The neural basis of predicate-argument structure[END_REF]. Presented in this way, predication looks like a quite banal capacity that must be shared with many animals. We have stressed elsewhere the fundamental difference that exists between categorisation and argumentative predication as it is expressed through language 1 [START_REF] Dessalles | Object recognition is not predication -Commentary on James R. Hurford: 'The neural basis of predicate-argument structure[END_REF]. Language predication would be a recent acquisition of our lineage. Its emergence gave rise, in two steps, to the appearance of the ability to master syntactic relations.

By proposing this scenario, we are aware of sending part of the mystery of the evolution of language competence back to the semantic realm. The syntactic expression of the main predication, and then of secondary predications, ceases to be miraculous, but the improbability of the transition from protolanguage to language seems to rest entirely on the cognitive abilities that allow us to think of such predications. We fully accept the consequences of such a change of perspective, which can be summarised as follows.

-First step: a new semantic ability emerges through which individuals can form predicative relations for argumentative purposes [START_REF] Dessalles | Aux origines du langage : Une histoire naturelle de la parole[END_REF]. A first form of syntax then appears to express these predications, with one simple clause for each predication. Expressing the relations between the predicate and its arguments is carried out by systems like inflection (case, gender, classes…) or position.

-Second step: a new semantic use of predication emerges. Predicates can be used as constraints to help in the determination of objects of discourse. New syntactic tools then _______ 1 One fundamental difference is that language predication, contrary to categorisation, can be systematically and explicitly negated in context: This object is not a book because it is not made of paper. Language predication can be formed in context by a mental operation of contrast between representations [START_REF] Ghadakpour | Le système conceptuel, à l'interface entre le langage[END_REF].

appear to express these auxiliary predications. The principle of semantic linking is used to locally link predications together. The recursive embedding of phrases and long range dependencies emerge as efficient tools to express predication linking.

When taking simulation studies on language evolution into account, one may rightfully consider that the emergence of these syntactic tools has no miraculous character, as soon as the corresponding semantic abilities are supposed to be present. By contrast, it is difficult, in the present state of knowledge, to assess the odds for the emergence of the ability to form mental predication.

Conclusion

By modelling the synchronisation between syntax and semantics, we were able to distinguish two important functions of syntax: the argumental function and its role in implementing determination. We suggested that these two functions emerged successively. The former, implemented mainly through inflection and word position, fulfils the role of expressing the main predication that is used at the argumentative interface. The latter, implemented through phrase embedding and long range dependencies, allows using auxiliary predications to help listeners constrain the objects of discourse.

The scenario we just proposed relies on a simplified model of the syntax-semantics interface. Syntax includes various other refinements that were left aside for the sake of simplicity. Our objective was to sketch a simple framework, a two-step scenario, on which it is possible to add further hypotheses concerning other features of language. We wanted to enhance the contrast between the devices used for the expression of the main predication and those used for auxiliary ones, by highlighting that recursion and long range dependencies serve only the second function.

What prompted the transition, in our scenario, is not the emergence of a new syntactic competence, but the emergence of a new semantic ability. By forming predicates, by expressing them through simple utterances, and then through molecular sentences to achieve a precise determination of discourse objects, our ancestors were able to assert relations and put into question the relations asserted by others. In conformity with what is generally considered, we have all reasons to think that this transition corresponds to the emergence of homo sapiens.

Acknowledgments

I thank Laleh Ghadakpour who accepted to read an earlier version of this paper. I would like to express my gratitude to the persons who promoted the CNRS initiative "Origine de l'Homme, du Langage et des Langues", which put the issue of the origins of language back into the French scientific debate.


Jean-Louis Dessalles
email: dessalles@telecom-paristech.fr

Laleh Ghadakpour

Object recognition is not predication

Predicates involved in language and reasoning are claimed to radically differ from categories applied to objects. Human predicates are the cognitive result of a contrast between perceived objects. Object recognition alone cannot generate such operations as modification and explicit negation. The mechanism studied by Hurford constitutes at best an evolutionary prerequisite of human predication ability.

Jim Hurford's claim is an impressive attempt to ground human distinctive cognitive abilities like logical reasoning and language in mammalian brain anatomy. His claim is conceptually important to help us understand how a dual where-and-what processing, leading to object recognition, may be a likely prerequisite of human predication. The claim that object recognition and predication are similar by nature, differing only in degree, is however too difficult to accept, for two groups of reasons. The first objection is a general critique that can be addressed at any gradualist account of phylogenetic descent. Modern evolutionary theory emphasizes that species are most of the time in equilibrium, and qualitatively differ by clear-cut characteristics [START_REF] Gould | Punctuated equilibria : the tempo and mode of evolution reconsidered[END_REF]. This view is widely confirmed by computer simulations based on genetic algorithms, which show that evolutionary processes are rapid and produce local optima [START_REF] Holland | Adaptation in natural and artificial systems[END_REF][START_REF] Dessalles | L'ordinateur génétique[END_REF]. One characteristic that our species has in proper is the cognitive ability to manipulate predicates through logical reasoning and to express them through language. The object recognition behaviour shown by mammals is not expected to be either equivalent to, or even to be a draft of, this human ability. One further argument along this line is provided by successful attempts to evolve syntactic language in populations of artificial individuals, as soon as they are granted with some predicate-argument semantics [START_REF] Kirby | Syntax without natural selection: how compositionality emerges from a vocabulary in a population of learners[END_REF][START_REF] Batali | The negotiation and acquisition of recursive grammars as a result of competition among exemplars[END_REF]). The fact that other primates seem unable to master syntactic symbolic expressions casts doubt on predicates being available to them. The second objection against equating object recognition abilities with (even simple) predication comes from the fact that the underlying cognitive processes are qualitatively different. Jim Hurford restrains the cognitive role of predication to the process of categorisation, "[…] the mental events involved when a human attends to an object in the world and classifies it perceptually as satisfying the predicate in question". When a perceived object is categorised as an apple, many perceptual features are involved in the recognition: aspects of the shape, colours, textures, presence of two characteristic extremities, etc. This ends up, according to Hurford's account, with a predicate like APPLE(x). Let us call this process, based on mere object recognition, R-predication. Contrary to Hurford's account, we claim that R-predication is qualitatively different from those cognitive processes involved in language that logic represents with predicates. Let us call the latter C-predication. Available models of categorisation, and thus of R-predication, are holistic. Neural networks or standard statistical devices rely on the maximum number of common features that can be found between the object to be recognised and known classes, exemplars or prototypes. The difficulty, addressed for instance in conceptual clustering techniques [START_REF] Michalski | Learning from Observation: Conceptual Clustering[END_REF], is precisely to extract short explicit descriptions for classes and objects. C-predication radically differs by showing non-holistic features: it isolates one explicit property from the context. In [START_REF] Ghadakpour | Le système conceptuel, à l'interface entre le langage[END_REF]), this process is described as resulting from a contrast operator (hence C meaning contrast in C-predication). We are able, without any training, to contrast any object with another resembling object or with its known prototype. This allows us to characterise a perceived object as a blue apple or as a big apple. Even if the remarkable ability to form prototypes and to see global resemblance between two objects is well within the reach of any mammalian brain, there is little reason to believe that we share with other animals the general ability to isolate relevant distinctive properties. Let us mention two reasons. First, our ability to modify names, like in a big flea, has little to do with the co-occurrence of a general property and a location. As Hurford rightfully remarks, the adjective big has to be understood here in the flea context [START_REF] Kamp | Prototype theory and compositionality[END_REF]. A writing like BIG(x) & FLEA(X) cannot represent this contextual effect, and hides the proper cognitive processing. In our own account, both the adjective big and the scale on which it is interpreted are provided by the contrast operator. The perceived object contrasts with the prototype of flea by its size; the scale (millimetres vs. metres or light-years) comes from the standard deviation of the prototype; the position of the perceived object on the scale is given by the magnitude of the contrast on this scale. Holistic object recognition (R-predication) does not offer means to pick a relevant axis and an appropriate scale, so adjectivename modification is strictly beyond its reach. The second reason why C-predication radically differs from R-predication is that the former can systematically lead to explicit negation. When performing explicit negation, one has to contrast the perceived object with some prototype and to exclude the former from the latter. You may say this is not a flea, because it is too big, or this is not a star, because it is too big. R-predication alone, because it is holistic, cannot offer such explicit negation. It can only refuse class membership by measuring a holistic distance and comparing it to some threshold. Yet, every human being has the ability to perform explicit negation on any domain without any specific training. This endowment, which underlies the argumentative use of language, is a consequence of our ability to contrast perceptions and form C-predicates. We suggested elsewhere why this ability can be considered as one of the main cognitive differences that distinguishes homo sapiens [START_REF] Dessalles | Aux origines du langage: Une histoire naturelle de la parole[END_REF]. It offered a new adaptation, namely the possibility to detect lies. By contrasting one's own perception with the liar's report, one may not only disbelieve the report, but also offer an explicit reason why the report should be rejected. Similarly, because they can be systematically negated, the predicates used in logical accounts of human thinking are C-predicates, not Rpredicates. The fact that C-predicates can be used to make membership explicit (this is a galaxy, because it is big) may explain why they are mistakenly supposed to be necessary for any categorisation, and hence imprudently granted to animals. The scope of Hurford's argument is thus more limited than anticipated, since it cannot be extended to "genuine" predication, what we called C-predication. The author's insight and the comprehensive line of argument that he draws from it could yet be extended in some way to C-predication. Our ability to "locate" an object on the axis provided by the contrast operator may be an evolutionary derivative of the fundamental ability to handle location and property separately. In order to say that this apple is big or that it is bigger than that apple, we must assign positions to objects, not in physical space, but on the contrast axis, which may be, in some cases, quite abstract.


Philibert Iacconi Laurent Poupon

Christophe Pijolat


Eric Papin

Philippe Grosseau

Bernard Guilhot

Mourad Benabdesselam

Philibert Iacconi

Point defects in alumina studied by thermoluminescence

ouverte pluridisciplinaire HAL, est destinée au dépôt


Alexandre Fabre

Christine Martinez-Vinson

Bertrand Roquelaure

Chantal Missirian

Nicolas Andre

Anne Breton

Alain Lachaux

Odul Egritas

Virginie Colomb

Julie Lemale

Nicolas André

Egritas Odul

Jean-Pierre Cézard

Olivier Goulet

Jacques Sarles

Nicolas Levy

Dr Catherine Badens

Novel mutations in TTC37 associated with Tricho-Hepato-Enteric syndrome

Keywords: Syndromic diarrhea, Tricho-hepato-enteric syndrome, TTC37, intractable diarrhea, Woolly hair, Thespin, Stankler syndrome Syndromic Diarrhea, Intractable diarrhea, Tricho-Hepato-Enteric syndrome, Stankler syndrome, TTC37, woolly hair

Introduction

The Tricho-Hepato-Enteric syndrome (THE syndrome, OMIM n°222470) also known as Syndromic Diarrhea, is a rare and severe autosomal recessive condition which associates intractable diarrhea with facial dysmorphism, intrauterine growth retardation, immunodeficiency with low serum concentrations of immunoglobulins, and hair abnormalities characterized by woolly hair [START_REF] Girault | Intractable infant diarrhea associated with phenotypic abnormalities and immunodeficiency[END_REF][START_REF] Verloes | Tricho-Hepato-Enteric Syndrome: Further Delineation of a Distinct Syndrome With Neonatal Hemochromatosis Phenotype, Intractable Diarrhea, and Hair Anomalies[END_REF].

Parenteral nutrition is usually started in the first weeks of life and maintained all life long in most cases. The liver failure is inconstant and when present, it is observed initially or later on in life. In the past, the presence or absence of liver failure led one to describe 2 different syndromes but it is now admitted that the 2 entities represent 2 sides of the same disease [START_REF] Fabre | Intractable diarrhea with "phenotypic anomalies" and tricho-hepato-enteric syndrome: two names for the same disorder[END_REF][START_REF] Goulet | Syndromic (phenotypic) diarrhea in early infancy[END_REF]. Death can occur early in life even though some patients can reach the third decade.

In the past few years, we collected samples for 12 patients from 11 families, all presenting a typical phenotype of THE syndrome. We first excluded several functional candidate genes [START_REF] Fabre | Exclusion of EGFR, HRAS, DSP, JUP, CTNNB1, PLEC1 and EPPK1 as functional candidate genes in 7 families with Syndromic Intractable Diarrhea[END_REF] and then performed a linkage analysis in order to unravel the genetic basis of this syndrome. In 2 of the 3 consanguineous families, homozygosity mapping identified a 5Mb region in 5q as a potential locus for the disease.

Very recently, Hartley et al described molecular defects causative for THE syndrome in TTC37 (NM_014639), a gene encoding for a putative protein named Thespin. Their study reported 9 mutations transmitted in a recessive pattern in 12 patients presenting this syndrome.

Since TTC37 maps in 5q, we assumed that this gene may be responsible for the disease in some of our patients and so performed systematic sequencing of genomic DNA samples. In this paper, we describe 11 novel TTC37 mutations in 9 patients out of 12 and provide clinical

Material and methods:

Patients

Patients and family members were assessed under approved human subject protocols and all participants provided informed consent.

Molecular studies

DNA was isolated from blood via a standard manufacturer's protocol (QIAamp DNA blood minikit, QIAgen). To analyse the TTC37 gene, direct sequencing was performed, after PCR amplification of the 43 exons and intronic flanking sequences, on an ABI 3130XL (Applied Biosystems).

The TTC37 genomic sequence from GenBank accession numbers NM_014639 was used as reference sequence. Detailed protocols and primer sequences are available on request. Two non-mutated patients and one heterozygous were tested by CGH array using the commercial Agilent 2x400K SurePrint G3 Human CGH Microarray (Agilent Technologies) array with the overall median probe spacing of 5,3 kb. Total RNA from 3 patient samples was prepared from lymphoblastoid cells and reverse transcribed using M-MLV (Sygma). Normal expression pattern was investigated by qPCR on a panel of normal transcripts from various tissues (Rapid-Scan cDNA panel, OriGene) using a probe located on exon-intron junction 35-36 of TTC37 and compared to GAPDH expression in duplex reactions. qPCR were done in triplicates and 2 sets of experiments were performed.

Bioinformatics analysis

The topology of normal and mutated Thespin protein was analysed using the algorithms proposed at TMpred (http://www.ch.embnet.org/software/TMPRED_form.html), TOPPRED

Results

Patients phenotype

The clinical features of the 12 patients are summarised in table 1. Detailed clinical data were previously published for 3 of them [START_REF] Fabre | Intractable diarrhea with "phenotypic anomalies" and tricho-hepato-enteric syndrome: two names for the same disorder[END_REF], Egritas et al 2010). All the 12 patients presented the 3 major signs of THE syndrome i.e. dysmorphism, hair abnormalities and intractable diarrhea. Among the 12 patients, one died of septicemia at age 10, 2 have stopped parenteral nutrition and 1 never required it.

Identification and characterization of novel TTC37 mutations in THE patients

Screening for mutations of TTC37 coding sequence and intron-exon junctions of DNA samples from THE patients identified 10 novel non ambiguous mutations in homozygous or compound heterozygous condition, in 8 (out of 12) patients. In addition, one patient presented only a heterozygous missense mutation. The mutations were spread along the gene: 3 were nonsense or frameshift mutations in the coding sequence leading to premature stop codon, 5

were mutations affecting splice sites either by substitution or deletion and 3 were missense mutations. All the parents of mutated patients were investigated and carried a mutation in heterozygous condition. The location and predicted consequences of the mutations on protein expression or function are reported in table 2.

Two of the 3 patients without mutation and the one with a single heterozygous mutation were investigated by whole genome CGH array with 17 probes mapping in TTC37. No CNV of the TTC37 region or of other regions could be identified.

Pattern of expression

Quantitative expression in normal tissues was assessed in a panel of 48 different tissues and revealed that TTC37 is widely expressed with the highest levels observed in vascular tissues, lymph node, pituitary, lung and intestine. Noticeably, we did not find any expression in the liver (figure 2).

Bioinformatics

In silico protein predictions were performed to propose a putative structure for Thespin and to evaluate the potential effect of TTC37 mutations identified in this study. The algorithm results are in accordance to predict that Thespin is mostly cytosolic and may contain 4 transmembrane domains (Figure 3). With all algorithms used in this study, several tetratricopeptide repeats (TPR) domains are predicted and their number varies from 5 to 22.

Discussion

Mutations previously identified in THE syndrome are heterogeneous and include frameshift, nonsense and splice site mutations. Here, we describe further 11 different mutations that add heterogeneity to the molecular genetics of THE syndrome (figure 3). These 11 novel mutations, in addition to the 9 mutations previously described, indicate strongly that TTC37 is the main gene responsible for THE syndrome. There is no clear hot spot region for mutations to date. As we exclude the presence of an intragenic deletion or duplication on the other allele, we assume that a non-identified intronic substitution producing an aberrant splicing is probably associated with the missense mutation.

The phenotypes of the 3 patients who did not carry any mutation in TTC37 have been carefully re-evaluated and were confirmed as being typical THE syndrome, suggesting strongly that at least one other gene may be implicated in this disease.

Multi-tissue transcript expression analysis showed wide expression of TTC37 mRNA with a high expression level in intestinal tissue but not in the liver, indicating that liver dysfunction observed in THE syndrome is probably secondary to another genetic cause or to long term parenteral nutrition. More surprising is the high level of expression observed in vein, arteria and lung as no abnormalities have been noticed in these tissues.

Up to date, the function of Thespin is unknown. We identified orthologs of human TTC37

using HomoloGene (www.ncbi.nlm.nih.gov/homologene) and found a nucleotide sequence conservation in canis (92%), bos (92%), rattus (83%), mus (82%), gallus (66%), danio (55%)

and drosophila (27%) in favour of an essential role for Thespin.

Protein motifs and domains are predicted in Thespin by several algorithms such as TMpred, PSORT and TOPPRED. Four transmembrane domains located in the C-terminal half of the protein are predicted, the last one in the C-terminal part being predicted with a stronger score.

The putative protein also contains several tetratrico-peptide repeats (TPR) domains which are structural motifs consisting of 34 Amino acid residues and found in over 300 human proteins 'andrea et al, 2003). Despite the fact that the amino-acids are poorly conserved, these motifs assemble into a characteristic Helix-Turn-Helix structure. The basic function of these TPR motifs is to mediate protein-protein interactions and therefore, can be involved in a variety of biological process such as cell-cycle regulation, transcriptional control, protein transport or folding. Consequently, no hint is given by the presence of TPR domains regarding a specific function. Interestingly, one of the splice site mutations of this series leads to a deletion of 19 residues in frame, following the skipping of exon 25. This deletion does not modify the predicted transmembrane domains but deleted several putative TPR domains of the C-terminal part, suggesting a major functional role for these structures.

Beside the TPR domains, neither the gene nor its derived protein show any significant sequence similarity to other known human DNA or protein sequences. In the literature, mutations in other TPRs containing proteins have been described as causative in several neurological human diseases such as Leber congenital amaurosis [START_REF] Sohocki | Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis[END_REF] or CMT type 4C [START_REF] Senderek | Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy[END_REF] but no clear link can be made between these proteins and their putative function.

Collectively, our results confirmed the role of TTC37 in THE syndrome, extended the pattern of mutations associated with this syndrome and provided new data on the normal expression pattern of TTC37 and the putative structure of Thespin. Assigning an unknown protein to a specific disease as done for THE syndrome, may enable one to describe new protein functions and will lead surely to characterize the localisation and functional properties of Thespin.

  and non mutated patients together with normal patterns of TTC 37 expression in several tissues.

  splice sites mutations on sequence transcripts were analysed by direct sequencing of RNA transcripts from lymphoblastoid cells, for 3 patients. The tested samples exhibited abnormal sequence due to the modification of splicing: skipping exon 23 in the case of the c.2515+1 C>G mutation, leading to a frameshift and creation of a premature stop codon (figure1a); skipping exon 25 in the case of the c.2577-3_-7delTTTT, leading to the deletion of 19 amino-acids in frame (figure1b); cryptic splice activation in exon 42 in case of the c.4620+1 G>C mutation promoting an alternative splicing and the replacement of the 41 terminal amino-acids by 61 others.

  in 70% of the mutated alleles(Hartley et al 2010 and our study), the mutation is localised in the 3' half of the gene. Most of the mutations are nonsense, frameshift or splice mutations that are predicted to produce premature stop codon. At least, 2 of the 3 missense mutations might affect splicing as well, as they are located in the vicinity of splice sites. For one of the patients, a single missense mutation in heterozygous condition has been identified

  Figure 1:

Figure 2 :

 2 Figure 2:

  Figure 3:

  (http://www.mobyle.pasteur.fr/cgi-bin/portal.py?form=Toppred), PSORT II

	F o r
	P
	e
	e r
	R
	e
	v i e
	w

(http://psort.ims.u-tokyo.ac.jp) and SMART (http://smart.embl.de/smart/show_motifs.pl) Predicted effects of missense mutations were obtained on Polyphen website (http://genetics.bwh.harvard.edu/pph).

Table 1 :

 1 Clinical features of the 12 patients of this study and the 12 previously published by[START_REF] Hartley | Mutations in TTC37 cause trichohepatoenteric syndrome (phenotypic diarrhea of infancy)[END_REF]. Facial dysmorphism is characterized by hypertelorism, broad flat nasal bridge, prominent forehead; Observed hair abnormalities are sparse, fragile and uncombable hair with trichorrhexis nodosa. NR: not reported

	F o
	r
	P
	e e r
	R e v i e w

Table 2 . Mutations in TTC37, geographical origin and consanguinity in the families of the patients with THE syndrome (NM_014639; NP_055454)

 2

	Family
	identifier
	(number of	Mutation 1	Mutation 2
	affected
	individuals)

Page 17 of 16 John Wiley & Sons, Inc. Human Mutation

John Wiley & Sons, Inc.Human Mutation

Acknowledgements

We are grateful to the patients and family members for their participation in the study and warmly acknowledge Patrice Bourgeois, Pierre Cau and Claudine Schiff for their helpful discussion, Benedicte Arnaud-Pigneur and Noël Peretti for providing patient samples. This work was supported by the Assistance Publique-Hôpitaux de Marseille (AORC 2009).

Regarding missense mutations, predictions at the protein level, were done using Polyphen algorithm. For frameshift mutations, predictions are theoretical and for splice site mutations, experimental at the transcript level. Nucleotide numbering reflects cDNA numbering with +1 corresponding to the A of the ATG translation initiation codon in the reference sequence. The initiation codon is codon 1.


Niels Krabbe
email: nkkrabbe@snm.ku.dk

Mery Juiña

Aldo Fernando Sornoza

Marked population increase of Pale-headed Brush-finch Atlapetes pallidiceps in response to cowbird control

Keywords: Ecuador, Atlapetes pallidiceps, Critically endangered, population status, Cowbird control

The Pale-headed Brush-Finch Atlapetes pallidiceps is an emberizine finch confined to south-central Ecuador and critically endangered owing to cowbird parasitism and habitat loss. We report a marked increase in numbers of brush-finches after seven years of cowbird control, confirming that brood parasitism had been an important limiting factor, and that shooting with firearms can be an effective method of controlling local cowbird parasitism.

Zusammenfassung

Niels Krabbe

Introduction

Atlapetes pallidiceps was feared extinct for over two decades, when the discovery of a small population in the upper Yunguilla Valley in 1998 raised hope for its future survival (Agreda et al. 1999). A reserve to protect it was established by Fundación Jocotoco in 1999 with the purchase of 27 ha of land. Over subsequent years adjacent lots were added to the reserve, and by 2009 the reserve encompassed 150 hectares holding 94% of all known territories of A. pallidiceps. A study in 2002 found that parasitism by Shiny Cowbird Molothrus bonariensis seriously affected its breeding success, with nine of fifteen nests (61%) parasitized (Oppel et al. 2003(Oppel et al. , 2004)). Cowbird control by shooting was initiated in 2003. The present paper presents the number and turnover rate of territorial brush-finch males counted annually from 1999 to 2009 and examines trends in relation to cowbird control.

Methods

The number of territorial males was monitored annually by NK from 1999 to 2009. This was done during the first two weeks of March, when vocal activity was most pronounced, except for 1999 -2001, when the time of breeding had not yet been established and when counts were made on 23-26 February and 1-20 May (1999), 14-20 April (2000), and 5-12 Feb and 16-27 March (2001). Additional brief visits were also made during the dry season 1998-2001, in June, August, September, November and December. MJ spent several weeks in the reserve during much of the rainy season in 2002 (30 March-30 April), 2003(3 March-28 May), 2004(15 Feb-15 May), 2005(15 Feb-15 May), 2006(1 Feb-30 April), 2007(7-12 March and 6-7 April) and 2008 (10-16 March), searching for nests, ringing nestlings, and studying the behaviour of the species through careful observation.

Singing males were tape-recorded whenever possible. Playback of the species' song or duet was used in order to obtain more tape-recordings and to determine if individuals had been ringed with colour bands. Playback sometimes provoked birds from adjacent territories to vocalize, which aided in delimiting territories. The location of singing males was determined and mapped with a GPS. Males had unique song qualities that when first developed, varied little from year to year (Krabbe 2004), so double registration was minimized by comparing spectrograms of the songs recorded. Because birds did not sing during heavy rains and only sang consistently during 10-45 minutes after dawn and only for a limited number of days during the breeding season, it was not always possible to record all pairs, so, in addition to the actual count, an estimate was made of the total number of territories believed to be occupied. If the same individual had occupied a territory both the year before and the year after a count, it was counted as also being present there during the year of the count. In areas that could only be visited at times when general vocal activity was low, the number of occupied territories was estimated to be the same as the year before.

The annual turnover of singing males (Fig. 2) was estimated up until 2007 in order to better understand the population dynamics. It was measured for territories where males were tape-recorded on two subsequent years, and was calculated as the number of new males divided by the total number of males in these territories. Birds that had moved from one territory to another were not counted as new. Minimum and maximum values were calculated by ex-or including birds of questionable identity. Turnover was not measured after 2007 when there were too many birds to get sufficiently long taperecordings of each.

Cowbird control was undertaken by AS, who spent the entire breeding season every year from 2003 onwards (late February to early May) shooting cowbirds (Molothrus bonariensis), preferentially females, as soon as these approached or entered the reserve. Cowbirds collected were sexed, examined for stomach contents, prepared as study skins and deposited in Museo Ecuatoriano de Ciencias Naturales, Quito.

Results

Number of occupied territories

The annual numbers of territorial males counted and estimated are shown in Fig. 1. Estimates were usually the same as or slightly higher than the number counted. Notable exceptions were 1999, 2000 and 2002, when only half of the breeding grounds were visited, and 2009, when breeding was delayed. The estimates from those years are thus less accurate than for other years, especially 1999 and 2000 when counts were not made during the peak song season.

Cowbird control

Cowbird control beginning in 2003 virtually removed cowbird parasitism altogether, with only a single nest parasitized in 2003, and one in 2005. Except for the first year, the number of adult cowbirds appearing in the reserve did not diminish significantly over the years (Table 1). Males appeared to outnumber females by a factor of two to four and formed conspicuous displaying groups. Females followed these groups or visited them briefly. Most cowbirds were collected in late February and in March, but a variable proportion (7-27%) was taken later (latest female collected April 23rd, latest male May 1st). Dark morph females were found to be so similar to males that they could not be safely sexed at a glance in the field.

A steady rise in numbers of occupied brush-finch territories started in 2004, the year after beginning of cowbird control, and continued until the end of the survey in 2009, when the number of territorial males had increased from less than 40 to 113 (Fig. 1).

Turnover

The annual number of males tape-recorded and number of territories where recordings were made on two subsequent years is given in Table 2. The turnover of singing males 1999-2007 (Fig. 2) averaged 40%, the same found between 1999 and 2002 (Krabbe 2004) but now supported by a larger sample size (156 vs. 40). The smallest turnover measured was 27%, the largest 47-62 %. Once established, males remained in their territory. They were found to have moved to a neighbouring territory on only three occasions (2%) and never to a more distant one.

Of sixty-four birds colour ringed as fledglings only six were reliably recorded in subsequent years, in part because many of them had lost one or both colour rings. One of the six was mated and had established a territory when one year old, whereas five were first recorded to have a territory when two years old. At least two of the latter five were still in their territory the following year. Some birds gave infrequent, incomplete, weak songs and were presumed to be one-year olds. Such birds were more prone to being overlooked than others. The oldest bird known had a exceptionally distinctive song and was tape-recorded in the same territory every year from 1999 until 2009, by which time it must have been at least 12 years old and was probably older, as it was already pale-headed and had a fully developed song when first recorded.

Discussion

The apparent increase in brush-finch pairs from 1999 to 2001 (Fig. 1) may have been caused in part by slight improvements of habitat during this time (Krabbe 2004) but are more likely the result of underestimates in 1999 and 2000, when counts were not made during the peak song season. The marked increase in the number of occupied territories after cowbird control was initiated (Fig. 1) on the other hand, is certainly genuine and is evidence that cowbird parasitism had been a major factor in limiting the population size. This is corroborated by the absence of the brush-finch from several patches of seemingly suitable habitat elsewhere in the valley system (Krabbe 2004).

That an increase was discernible after just one year of cowbird control probably indicates that more brush-finches establish territories when only one year old than the few observed colour ringed birds suggests. Early recruitment would also help explain the relatively high turnover rate found.

As evident from figures 1 and 2, the population has not yet reached a saturation point. Based on the observed average territory size of 1 ha and minimum size of 0.5 ha (Krabbe 2004), we expect the population to increase to between 150 and 200 territories, if habitat is managed.

Although shooting of cowbirds has previously been suggested as a feasible method of control (Smith et al. 2000), the efficiency of shooting versus trapping has only been studied recently (Summers et al. 2006a,b). In the upper Yunguilla Valley shooting has proved effective, perhaps in part due to the local topography (all cowbirds coming from the same direction), and partly to the use of a determined and skilled controller. Considering that new cowbirds keep appearing through the breeding season of the brush-finch, and that a single Shiny Cowbird female presumably lays as many as 40 eggs in a season, as known to be the average for the closely related Brown-headed Cowbird (Molothrus ater) (Scott & Ankney 1980), we suggest that cowbird control in future years continues to cover the peak period of laying from mid February to mid April.

Agreda A, Krabbe N, Rodriguez O (1999) Figure 2. Turnover of territorial males of Atlapetes pallidiceps measured as the number of territories where a new male had replaced the one from the year before, divided by the number of territories where males were tape-recorded both years (n). The turnover was between 27 % and 62 % and averaged 40 %.

Deutlicher

  Populationsanstieg der Blasskopf-Buschammer Atlapetes pallidiceps als Antwort auf die Bestandsregulierung von Kuhstärlingen Die Blasskopf-Buschammer Atlapetes pallidiceps ist eine Ammer, die nur in Südzentralecuador vorkommt und durch Kuhstärlings-Parasitismus und Habitatverlust vom Aussterben bedroht ist. Wir berichten von einer deutlichen Zunahme der Buschammernzahl nach siebenjähriger Bestandsregulierung von Kuhstärlingen und bestätigen somit, dass Brutparasitismus ein wichtiger limitierender Faktor gewesen war und das Schießen von Kuhstärlingen mit Schusswaffen eine effektive Methode sein kann, Kuhstärlings-Parasitismus lokal zu kontrollieren.

Figure 1 .

 1 Figure 1. Number of territories occupied by Atlapetes pallidiceps 1999-2009. Slanting lines indicate years with cowbird control. Estimates from 1999 and 2000 are not from peak song season and may be too low.

Table 1 .

 1 Pale-headed Brush-finch Atlapetes pallidiceps is not extinct. Cotinga 11:50-54 Number of cowbirds killed in the Yunguilla Reserve 2003-2009. Females were shot preferentially, increasingly so in later years, so the numbers do not reflect the natural sex ratios.

	Krabbe N (2004) Pale-headed Brush-finch Atlapetes pallidiceps: notes on population
	size, habitat, vocalizations, feeding, interference competition, and conservation. Bird
	Conservation International 14:77-86
	Oppel S, Schaefer HM, Schmidt V (2003) Description of the nest, eggs, and breeding
	behavior of the endangered Pale-headed Brush-Finch (Atlapetes pallidiceps) in
	Ecuador. Wilson Bulletin 115:360-366
	Oppel S, Schaefer HM, Schmidt V, Schröder B (2004) Cowbird parasitism of Pale-
	headed Brush-finch Atlapetes pallidiceps: implications for conservation and
	management. Bird Conservation International 14:63-75
	Scott, DM, Ankney, CD (1980) Fecundity of the Brown-Headed Cowbird in Southern
	Ontario. The Auk 97:677-683
	Smith J NM, Cook TL, Robinson SK, Rothstein SI, Sealy SG (2000) Ecology and
	Management of Cowbirds and Their Hosts: Studies in the Conservation of North
	American Passerine Birds. University of Texas Press
	Summers SG, Stake MM, Eckrich GH, Kostecke RM, Cimprich DA (2006a) Reducing
	cowbird parasitism with minimal effort shooting: a pilot study. The Southwestern
	Naturalist 51:409-411
	Summers SG, Kostecke RM, Norman GL (2006b) Efficacy of trapping and shooting in
	removing breeding brown-headed cowbirds. Wildlife Society Bulletin 34:1107-1112
	Year	2003	2004	2005	2006	2007	2008	2009
	Females	22	11	6	6	17	19	10
	Males	47	19	20	12	20	17	13
	Both sexes	69	30	26	18	37	36	23

Table 2 .

 2 Number of territorial males of Atlapetes pallidiceps tape-recorded 1999-2007 and number of territories where tape-recordings had also been obtained the previous year.

Acknowledgments

We thank Francisco Sornoza, Enrique Calle, Braulio Carlos, H. Martin Schaefer, Veronica Schmidt, Steffen Oppel, Joan Heathcove, Verónica Ordoñez, Lucas Achig, Rolando Carpio, Rocío Guevara, Dayanara Sanchéz, Harold Greeney, Brett Scheffers and Rudi Gelis, who all contributed to the study; H. Greeney and H. M. Schaefer provided useful comments on the manuscript. The field work was funded by the Jocotoco Foundation and in 2002 and 2003 also by the RSPB and the Sweden Club 300.