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Selection on Different Genes with Equivalent Functions: the Convergence Story Told by Hox Genes Along the Evolution of Aquatic Mammalian Lineages Mariana F

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Selection on Different Genes with Equivalent Functions: the Convergence Story Told by Hox Genes Along the Evolution of Aquatic Mammalian Lineages Mariana F Nery et al. BMC Evolutionary Biology (2016) 16:113 DOI 10.1186/s12862-016-0682-4 RESEARCH ARTICLE Open Access Selection on different genes with equivalent functions: the convergence story told by Hox genes along the evolution of aquatic mammalian lineages Mariana F. Nery1*, Brunno Borges2, Aline C. Dragalzew2 and Tiana Kohlsdorf2* Abstract Background: Convergent evolution has been a challenging topic for decades, being cetaceans, pinnipeds and sirenians textbook examples of three independent origins of equivalent phenotypes. These mammalian lineages acquired similar anatomical features correlated to an aquatic life, and remarkably differ from their terrestrial counterparts. Whether their molecular evolutionary history also involved similar genetic mechanisms underlying such morphological convergence nevertheless remained unknown. To test for the existence of convergent molecular signatures, we studied the molecular evolution of Hox genes in these three aquatic mammalian lineages, comparing their patterns to terrestrial mammals. Hox genes are transcription factors that play a pivotal role in specifying embryonic regional identity of nearly any bilateral animal, and are recognized major agents for diversification of body plans. Results: We detected few signatures of positive selection on Hox genes across the three aquatic mammalian lineages and verified that purifying selection prevails in these sequences, as expected for pleiotropic genes. Genes found as being positively selected differ across the aquatic mammalian lineages, but we identified a substantial overlap of their developmental functions. Such pattern likely resides on the duplication history of Hox genes, which probably provided different possible evolutionary routes for achieving the same phenotypic solution. Conclusions: Our results indicate that convergence occurred at a functional level of Hox genes along three independent origins of aquatic mammals. This conclusion reinforces the idea that different changes in developmental genes may lead to similar phenotypes, probably due to the redundancy provided by the participation of Hox paralogous genes in several developmental functions. Keywords: Cetaceans, Pinnipeds, Sirenians, Molecular evolution, Hox genes, Positive selection Background aquatic living. Their streamlined body shape minimizes The aquatic mammals – cetaceans (whales, dolphins and drag, increases performance and reduces transport ener- porpoises), pinnipeds (sea lions, seals and walruses) and getic costs [1]. Drag is also decreased by the presence of sirenians (manatees and dugongs) – represent three ex- either a strikingly reduced pelvic appendicular skeleton tant mammalian lineages that independently recolonized or hindlimbs extremely modified and enlarged propul- the aquatic environment. Remarkably, these three groups sive appendices [2]; these animals also evolved a pair of encompass convergent anatomical and physiological so- paddle-shapes fore-flippers, equivalent to the forelimbs lutions that accommodate the several challenges of of terrestrial mammals. In all cases, water recolonization involved extensive morphogenetic reorganization and * Correspondence: [email protected]; [email protected] modification of several physiological features [3]. Com- 1 Departamento de Genética, Evolução e Bioagentes, Instituto de Biologia, parative anatomy and the fossil record have substantially Universidade Estadual de Campinas, Campinas, Brazil 2Departamento de Biologia, FFCLRP, Universidade de São Paulo, Ribeirão elucidated these evolutionary transitions towards the Preto, Brazil © 2016 Nery et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Nery et al. BMC Evolutionary Biology (2016) 16:113 Page 2 of 9 aquatic life (especially in cetaceans, see [4, 5]). But only evolution in these aquatic lineages that secondarily and recently, the molecular mechanisms underlying such independently recolonized the sea, by characterizing and dramatic and convergent morphological changes during comparing the coding regions of Hox genes in aquatic evolution of these three mammalian lineages began to and terrestrial mammals. Specifically, we test whether be unraveled (e.g. [6–13]). Hox genes underwent different selective pressures in The convergent evolution of similar traits in response aquatic mammals, in nucleotide and amino acid se- to equivalent selective pressures represents an excep- quences, and also whether there are molecular sig- tional opportunity to study which evolutionary pro- natures of these genes that endorse convergent cesses underlie specific phenotypic modifications developmental mechanisms during evolutionary transi- associated to the conquest of a new environment. Sev- tions towards re-colonization of aquatic environments. eral recent studies have been dedicated to evaluate the extent to which adaptive phenotypic convergence is at- Methods tributable to convergent changes at the molecular level In order to accomplish a wide taxonomic sampling, we [14–17]. Such articles so far demonstrated that conver- obtained unannotated genomic sequences in Ensembl gent evolution of similar phenotypes may or may not genome browser and in GenBank from the following 19 share similar molecular bases. Moreover, these similar- mammalian species: tasmanian devil (Sarcophilus harrisii), ities may occur at several genetic levels, meaning that microbat (Myotis lucifugus), elephant (Loxodonta theoccurrenceofconvergencemayinvolvethesame africana), manatee (Trichechus manatus), horse mutations in the same genes, but may also comprise (Equus caballus), dog (Canis familiaris), ferret (Mustela different and equivalent mutations in the same genes, putorius), Weddell seal (Leptonychotes weddellii), walrus or even mutations at different genes with equivalent (Odobesnus rosmarus), cow (Bos taurus), bottlenose dol- molecular functions [14–17]. phin (Tursiops truncatus), baiji dolphin (Lipotes vexilifer), Molecular bases engaged in the phenotypic minke whale (Balaenoptera acutorostrata), mouse (Mus reorganization that occurred during the three evolu- musculus), rabbit (Oryctologus cuniculus), human (Homo tionary events of return to the aquatic environment by sapiens), chimpanzee (Pan troglodytes), orangutan (Pongo mammalian lineages likely comprise transcription fac- abelli)andmarmoset(Callithrix jacchus). Despite the low tors essential for developmental processes. Among genome coverage of some species, the four Hox clusters these, Hox genesareidealcandidatestotestforassoci- (A, B, C and D) have been well sequenced, and were ations between molecular evolution and morphogenetic complete and located within single scaffolds for most spe- rearrangements. These transcription factors regulate cies, excepting the Weddell seal, which cluster A was in- patterning of specific body structures during develop- complete, cluster B was fragmented in two scaffolds, and ment by specifying regional identities along the clusters C and D were absent, the microbat, which had the anterior-posterior axis of all billaterian metazoans [18]. Cluster B fragmented in two scaffolds, and the baiji dol- Vertebrates, in particular, possess four distinct Hox phin, which Cluster C remained absent of databases. gene clusters (Hox A, B, C and D) located on different Genomic sequences of Hox genes from these species chromosomes, as a consequence of the two rounds of were manually annotated based on comparisons with whole genome duplications that occurred early in their known exon sequences available for humans, using the evolutionary history [19]. Their fundamental role in programs GenScan [33] and Blas2seq 2.2 [34]. To fur- patterning body morphology, together with their broad ther corroborate the orthologous relationships of each contribution to developmental processes (e.g. [20–25]), gene included in our analyses, we conducted phylogen- foster the assertion that variation in nucleotide se- etic reconstructions based on maximum likelihood, quences of Hox gene coding regions is usually associ- using the program RAxML [35]. Moreover, in order to ated to phenotypic differences [26–31]. As a maximize the number of orthologs in each analysis, we consequence, this gene family is often recognized as a conducted a search in GenBank for Hox genes from major agent for diversification of metazoan body plans other mammalian species. Using this approach, the spe- [19, 20]. Evaluation of molecular evolutionary patterns cies composition of each orthologous Hox gene varied of Hox genes in the context of independent origins of from 11 up to 38 species. It means that each Hox gene equivalent phenotypes, however, remains relegated [but had a unique phylogenetic tree, comprising the ortholog see[32]forarecentstudyonthetopic]. specific set of species recovered from sequenced ge- In this study we test for convergent signatures in Hox nomes or GenBank. After this verification of ortholo- genes by comparing sequences of three mammalian line- gous sequences we finally proceeded with the natural ages that are phenotypically
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