Abstract

Developmental processes and their results, morphological characters, are inherited through transmission of genes regulating development. While there is ample evidence that cis-regulatory elements tend to be modular, with sequence segments dedicated to different roles, the situation for proteins is less clear, being particularly complex for transcription factors with multiple functions. Some motifs mediating protein-protein interactions may be exclusive to particular developmental roles, but it is also possible that motifs are mostly shared among different processes. Here we focus on HoxA13, a protein essential for limb development. We asked whether the HoxA13 amino acid sequence evolved similarly in three limbless clades: Gymnophiona, Amphisbaenia and Serpentes. We explored variation in ω (dN/dS) using a maximum-likelihood framework and HoxA13sequences from 47 species. Comparisons of evolutionary models provided low ω global values and no evidence that HoxA13 experienced relaxed selection in limbless clades. Branch-site models failed to detect evidence for positive selection acting on any site along branches of Amphisbaena and Gymnophiona, while three sites were identified in Serpentes. Examination of alignments did not reveal consistent sequence differences between limbed and limbless species. We conclude that HoxA13 has no modules exclusive to limb development, which may be explained by its involvement in multiple developmental processes.

Highlights

  • Evolution of morphological diversity has fascinated biologists, but only in the past half-century the investigation of mechanisms underlying the origin and establishment of specific phenotypes became possible through the combination of genetics, evolution and developmental biology in the field so-called Evo-Devo (Evolution of Development, see Raff, 2000; Hall, 2012)

  • Because the branch-site model implemented in PAML can be limiting due to the necessary specification of foreground lineages and the assumption that w = 1 for all background lineages (Zhang et al, 2005), we examined HoxA13 for signatures of episodic selection using the mixed model of evolution (MEME, Murrell et al, 2012) and the fixed-effect likelihood (FEL) model of molecular evolution performed with HyPhy in Datamonkey server (Delport et al, 2010)

  • Identification of molecular signatures in HoxA13 that are common to independently derived limbless lineages would suggest the presence of limb-specific sequence segments in the protein, while no consistent sequence differences between limbed and limbless species suggests that all motifs involved in limb development are committed to other developmental functions

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Summary

Introduction

Evolution of morphological diversity has fascinated biologists, but only in the past half-century the investigation of mechanisms underlying the origin and establishment of specific phenotypes became possible through the combination of genetics, evolution and developmental biology in the field so-called Evo-Devo (Evolution of Development, see Raff, 2000; Hall, 2012). Provide a wide range of evidence supporting the contribution of mutations in coding regions of transcription factor genes for the diversification of phenotypes (Galant and Carroll, 2002; Lynch et al, 2008, Crow et al, 2009; Brayer et al, 2011) Such findings imply that transcriptions factors do not remain functionally equivalent during evolution (Galant and Carroll, 2002; Ronshaugen et al, 2002; Lynch et al, 2008; Crow et al, 2009), and that the adaptive evolution of transcription factors proteins may be involved in the origin of new phenotypes (Lynch et al, 2004; Lynch and Wagner, 2008; Crow et al, 2009; Brayer et al, 2011). Changes in a given sequence segment that plays two developmental roles likely affect both processes, as well as their results (i.e. the morphological characters established in the developing embryo), so that any motif involved in multiple developmental processes would be expected to be under pleiotropic constraint (for recent discussions about the topic see Pavlicev and Wagner, 2012; Pavlicev and Widder, 2015)

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