Evolutionary history of the iroquois/Irx genes in metazoans

<p>Abstract</p> <p>Background</p> <p>The <it>iroquois </it>(<it>iro/Irx</it>) genes encode transcriptional regulators that belong to the TALE superclass of homeodomain proteins and have key functions during development in both vertebrates and insects. The <it>Irx </it>genes occur in one or two genomic clusters containing three genes each within the <it>Drosophila </it>and several vertebrate genomes, respectively. The similar genomic organization in <it>Drosophila </it>and vertebrates is widely considered as a result of convergent evolution, due to independent tandem gene duplications. In this study, we investigate the evolutionary history of the <it>Irx </it>genes at the scale of the whole metazoan kingdom.</p> <p>Results</p> <p>We identified <it>in silico </it>the putative full complement of <it>Irx </it>genes in the sequenced genomes of 36 different species representative of the main metazoan lineages, including non bilaterian species, several arthropods, non vertebrate chordates, and a basal vertebrate, the sea lamprey. We performed extensive phylogenetic analyses of the identified <it>Irx </it>genes and defined their genomic organizations. We found that, in most species, there are several <it>Irx </it>genes, these genes form two to four gene clusters, and the <it>Irx </it>genes are physically linked to a structurally and functionally unrelated gene known as <it>CG10632 </it>in <it>Drosophila</it>.</p> <p>Conclusion</p> <p>Three main conclusions can be drawn from our study. First, an <it>Irx </it>cluster composed of two genes, <it>araucan/caupolican </it>and <it>mirror</it>, is ancestral to the crustaceans+insects clade and has been strongly conserved in this clade. Second, three <it>Irx </it>genes were probably present in the last common ancestor of vertebrates and the duplication that has given rise to the six genes organized into two clusters found in most vertebrates, likely occurred in the gnathostome lineage after its separation from sea lampreys. Third, the clustered organization of the <it>Irx </it>genes in various evolutionary lineages may represent an exceptional case of convergent evolution or may point to the existence of an <it>Irx </it>gene cluster ancestral to bilaterians.</p

Insights into the evolution of the snail superfamily from metazoan wide molecular phylogenies and expression data in annelids

<p>Abstract</p> <p>Background</p> <p>An important issue concerning the evolution of duplicated genes is to understand why paralogous genes are retained in a genome even though the most likely fate for a redundant duplicated gene is nonfunctionalization and thereby its elimination. Here we study a complex superfamily generated by gene duplications, the <it>snail </it>related genes that play key roles during animal development. We investigate the evolutionary history of these genes by genomic, phylogenetic, and expression data studies.</p> <p>Results</p> <p>We systematically retrieved the full complement of <it>snail </it>related genes in several sequenced genomes. Through phylogenetic analysis, we found that the <it>snail </it>superfamily is composed of three ancestral families, <it>snail</it>, <it>scratchA </it>and <it>scratchB</it>. Analyses of the organization of the encoded proteins point out specific molecular signatures, indicative of functional specificities for Snail, ScratchA and ScratchB proteins. We also report the presence of two <it>snail </it>genes in the annelid <it>Platynereis dumerilii</it>, which have distinct expression patterns in the developing mesoderm, nervous system, and foregut. The combined expression of these two genes is identical to that of two independently duplicated <it>snail </it>genes in another annelid, <it>Capitella spI</it>, but different aspects of the expression patterns are differentially shared among paralogs of <it>Platynereis </it>and <it>Capitella</it>.</p> <p>Conclusion</p> <p>Our study indicates that the <it>snail </it>and <it>scratchB </it>families have expanded through multiple independent gene duplications in the different bilaterian lineages, and highlights potential functional diversifications of Snail and ScratchB proteins following duplications, as, in several instances, paralogous proteins in a given species show different domain organizations. Comparisons of the expression pattern domains of the two <it>Platynereis </it>and <it>Capitella snail </it>paralogs provide evidence for independent subfunctionalization events which have occurred in these two species. We propose that the <it>snail </it>related genes may be especially prone to subfunctionalization, and this would explain why the <it>snail </it>superfamily underwent so many independent duplications leading to maintenance of functional paralogs.</p

Evolutionary changes in the notochord genetic toolkit: a comparative analysis of notochord genes in the ascidian Ciona and the larvacean Oikopleura

<p>Abstract</p> <p>Background</p> <p>The notochord is a defining feature of the chordate clade, and invertebrate chordates, such as tunicates, are uniquely suited for studies of this structure. Here we used a well-characterized set of 50 notochord genes known to be targets of the notochord-specific Brachyury transcription factor in one tunicate, <it>Ciona intestinalis </it>(Class Ascidiacea), to begin determining whether the same genetic toolkit is employed to build the notochord in another tunicate, <it>Oikopleura dioica </it>(Class Larvacea). We identified <it>Oikopleura </it>orthologs of the <it>Ciona </it>notochord genes, as well as lineage-specific duplicates for which we determined the phylogenetic relationships with related genes from other chordates, and we analyzed their expression patterns in <it>Oikopleura </it>embryos.</p> <p>Results</p> <p>Of the 50 <it>Ciona </it>notochord genes that were used as a reference, only 26 had clearly identifiable orthologs in <it>Oikopleura</it>. Two of these conserved genes appeared to have undergone <it>Oikopleura</it>- and/or tunicate-specific duplications, and one was present in three copies in <it>Oikopleura</it>, thus bringing the number of genes to test to 30. We were able to clone and test 28 of these genes. Thirteen of the 28 <it>Oikopleura </it>orthologs of <it>Ciona </it>notochord genes showed clear expression in all or in part of the <it>Oikopleura </it>notochord, seven were diffusely expressed throughout the tail, six were expressed in tissues other than the notochord, while two probes did not provide a detectable signal at any of the stages analyzed. One of the notochord genes identified, <it>Oikopleura netrin</it>, was found to be unevenly expressed in notochord cells, in a pattern reminiscent of that previously observed for one of the <it>Oikopleura </it><it>Hox </it>genes.</p> <p>Conclusions</p> <p>A surprisingly high number of <it>Ciona </it>notochord genes do not have apparent counterparts in <it>Oikopleura</it>, and only a fraction of the evolutionarily conserved genes show clear notochord expression. This suggests that <it>Ciona </it>and <it>Oikopleura</it>, despite the morphological similarities of their notochords, have developed rather divergent sets of notochord genes after their split from a common tunicate ancestor. This study demonstrates that comparisons between divergent tunicates can lead to insights into the basic complement of genes sufficient for notochord development, and elucidate the constraints that control its composition.</p

atonal- and achaete-scute-related genes in the annelid Platynereis dumerilii: insights into the evolution of neural basic-Helix-Loop-Helix genes

Functional studies in model organisms, such as vertebrates and Drosophila, have shown that basic Helix-loop-Helix (bHLH) proteins have important roles in different steps of neurogenesis, from the acquisition of neural fate to the differentiation into specific neural cell types. However, these studies highlighted many differences in the expression and function of orthologous bHLH proteins during neural development between vertebrates and Drosophila. To understand how the functions of neural bHLH genes have evolved among bilaterians, we have performed a detailed study of bHLH genes during nervous system development in the polychaete annelid, Platynereis dumerilii, an organism which is evolutionary distant from both Drosophila and vertebrates.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Origin and diversification of the basic helix-loop-helix gene family in metazoans: insights from comparative genomics

BACKGROUND: Molecular and genetic analyses conducted in model organisms such as Drosophila and vertebrates, have provided a wealth of information about how networks of transcription factors control the proper development of these species. Much less is known, however, about the evolutionary origin of these elaborated networks and their large-scale evolution. Here we report the first evolutionary analysis of a whole superfamily of transcription factors, the basic helix-loop-helix (bHLH) proteins, at the scale of the whole metazoan kingdom. RESULTS: We identified in silico the putative full complement of bHLH genes in the sequenced genomes of 12 different species representative of the main metazoan lineages, including three non-bilaterian metazoans, the cnidarians Nematostella vectensis and Hydra magnipapillata and the demosponge Amphimedon queenslandica. We have performed extensive phylogenetic analyses of the 695 identified bHLHs, which has allowed us to allocate most of these bHLHs to defined evolutionary conserved groups of orthology. CONCLUSION: Three main features in the history of the bHLH gene superfamily can be inferred from these analyses: (i) an initial diversification of the bHLHs has occurred in the pre-Cambrian, prior to metazoan cladogenesis; (ii) a second expansion of the bHLH superfamily occurred early in metazoan evolution before bilaterians and cnidarians diverged; and (iii) the bHLH complement during the evolution of the bilaterians has been remarkably stable. We suggest that these features may be extended to other developmental gene families and reflect a general trend in the evolution of the developmental gene repertoires of metazoans

Traffic Instabilities in Self-Organized Pedestrian Crowds

In human crowds as well as in many animal societies, local interactions among individuals often give rise to self-organized collective organizations that offer functional benefits to the group. For instance, flows of pedestrians moving in opposite directions spontaneously segregate into lanes of uniform walking directions. This phenomenon is often referred to as a smart collective pattern, as it increases the traffic efficiency with no need of external control. However, the functional benefits of this emergent organization have never been experimentally measured, and the underlying behavioral mechanisms are poorly understood. In this work, we have studied this phenomenon under controlled laboratory conditions. We found that the traffic segregation exhibits structural instabilities characterized by the alternation of organized and disorganized states, where the lifetime of well-organized clusters of pedestrians follow a stretched exponential relaxation process. Further analysis show that the inter-pedestrian variability of comfortable walking speeds is a key variable at the origin of the observed traffic perturbations. We show that the collective benefit of the emerging pattern is maximized when all pedestrians walk at the average speed of the group. In practice, however, local interactions between slow- and fast-walking pedestrians trigger global breakdowns of organization, which reduce the collective and the individual payoff provided by the traffic segregation. This work is a step ahead toward the understanding of traffic self-organization in crowds, which turns out to be modulated by complex behavioral mechanisms that do not always maximize the group's benefits. The quantitative understanding of crowd behaviors opens the way for designing bottom-up management strategies bound to promote the emergence of efficient collective behaviors in crowds.Comment: Article published in PLoS Computational biology. Freely available here: http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.100244

Coe Genes Are Expressed in Differentiating Neurons in the Central Nervous System of Protostomes

Genes of the coe (collier/olfactory/early B-cell factor) family encode Helix-Loop-Helix transcription factors that are widely conserved in metazoans and involved in many developmental processes, neurogenesis in particular. Whereas their functions during vertebrate neural tube formation have been well documented, very little is known about their expression and role during central nervous system (CNS) development in protostomes. Here we characterized the CNS expression of coe genes in the insect Drosophila melanogaster and the polychaete annelid Platynereis dumerilii, which belong to different subgroups of protostomes and show strikingly different modes of development. In the Drosophila ventral nerve cord, we found that the Collier-expressing cells form a subpopulation of interneurons with diverse molecular identities and neurotransmitter phenotypes. We also demonstrate that collier is required for the proper differentiation of some interneurons belonging to the Eve-Lateral cluster. In Platynereis dumerilii, we cloned a single coe gene, Pdu-coe, and found that it is exclusively expressed in post mitotic neural cells. Using an original technique of in silico 3D registration, we show that Pdu-coe is co-expressed with many different neuronal markers and therefore that, like in Drosophila, its expression defines a heterogeneous population of neurons with diverse molecular identities. Our detailed characterization and comparison of coe gene expression in the CNS of two distantly-related protostomes suggest conserved roles of coe genes in neuronal differentiation in this clade. As similar roles have also been observed in vertebrates, this function was probably already established in the last common ancestor of all bilaterians

Neurofilament depletion improves microtubule dynamics via modulation of Stat3/stathmin signaling

In neurons, microtubules form a dense array within axons, and the stability and function of this microtubule network is modulated by neurofilaments. Accumulation of neurofilaments has been observed in several forms of neurodegenerative diseases, but the mechanisms how elevated neurofilament levels destabilize axons are unknown so far. Here, we show that increased neurofilament expression in motor nerves of pmn mutant mice, a model of motoneuron disease, causes disturbed microtubule dynamics. The disease is caused by a point mutation in the tubulin-specific chaperone E (Tbce) gene, leading to an exchange of the most C-terminal amino acid tryptophan to glycine. As a consequence, the TBCE protein becomes instable which then results in destabilization of axonal microtubules and defects in axonal transport, in particular in motoneurons. Depletion of neurofilament increases the number and regrowth of microtubules in pmn mutant motoneurons and restores axon elongation. This effect is mediated by interaction of neurofilament with the stathmin complex. Accumulating neurofilaments associate with stathmin in axons of pmn mutant motoneurons. Depletion of neurofilament by Nefl knockout increases Stat3-stathmin interaction and stabilizes the microtubules in pmn mutant motoneurons. Consequently, counteracting enhanced neurofilament expression improves axonal maintenance and prolongs survival of pmn mutant mice. We propose that this mechanism could also be relevant for other neurodegenerative diseases in which neurofilament accumulation and loss of microtubules are prominent features

Etude de l'évolution du système nerveux chez les animaux (neurogenèse comparative et phylogénomique)

L étude de l évolution du système nerveux des animaux s appuie principalement sur la comparaison morpho-anatomique de celui-ci chez différentes espèces et sur la comparaison des processus développementaux et génétiques dirigeant sa formation. Les animaux présentant une symétrie bilatérale, les Bilatériens, sont caractérisés par la présence d un système nerveux central et périphérique, ce qui soulève la question de son origine évolutive. Parmi les trois lignées des Bilatériens, les Deutérostomiens, les Ecdysozoaires et les Lophotrochozoaires, les études à même de répondre à cette question ont été menées quasi exclusivement chez les vertébrés (Deutérostomiens) et la drosophile (Ecdysozoaires). Cette thèse présente des données complémentaires chez un organisme appartenant aux Lophotrochozoaires, l annélide Platynereis dumerilii. Ces données fournissent des informations cruciales pour déterminer quels aspects de la neurogenèse sont ancestraux aux Bilatériens et quels sont ceux qui proviennent de dérives spécifiques à l une ou l autre lignée. A l aide d une approche gène candidat, plusieurs similitudes entre la neurogenèse des vertébrés et celle de Platynereis ont été mises en évidence, suggérant une conservation de l organisation ancestrale du système nerveux central et périphérique chez ces organismes. Ces résultats permettent également d avancer une hypothèse originale quant à l origine du tube nerveux des vertébrés. L approche gène candidat a été également complétée par des études phylogénomiques qui ont permis d élucider les histoires évolutives de familles de gènes, et d illustrer des phénomènes génomiques comme la duplication génique et la formation de complexes génique.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF