Molecular evolution of HoxA13 and the multiple origins of limbless morphologies in amphibians and reptiles

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.

Selection on different genes with equivalent functions: the convergence story told by Hox genes along the evolution of aquatic mammalian lineages

“…As a consequence, this gene family is often recognized as a major agent for diversification of metazoan body plans [ 19 , 20 ]. Evaluation of molecular evolutionary patterns of Hox genes in the context of independent origins of equivalent phenotypes, however, remains relegated [but see [ 32 ] for a recent study on the topic].…”

Peer Review #2 of "Comparative and evolutionary analysis of the reptilian hedgehog gene family (Shh, Dhh, and Ihh) (v0.1)"

“…Shh plays a crucial role in regulating vertebrate organogenesis, such as the development of digits on limbs. A different evolutionary rate of Shh was not found, as expected, which is likely because the mechanism of limb reduction in reptiles is regulated by other related genes, such as HoxA13 (Singarete et al 2015). The overall branches of Shh rejected the two-ratio model, suggesting that the reptilian Shh gene evolved at a relatively stable rate.…”

Evolutionary Developmental Biology (Evo‐Devo) Research in Latin America

“…Molecular evolution of HoxA13 and the multiple origins of limbless morphologies in amphibians and reptiles (Singarete et al., )…”

“…Another example of extreme body shape transformation that has been studied using nonmodel organisms is the convergent evolution of snakelike forms in Neotropical Squamata (lizards, snakes, and amphisbaenians), which involve limb reduction or loss along with an increase in the number of trunk vertebrae. Comparative anatomical and molecular studies suggest that convergent forms do not necessarily involve the same evolutionary changes in developmental processes and genetic pathways (Waters, ; Roscito et al., ; Singarete et al., ). Changes in the anatomy of the musculoskeletal system associated with limbless morphologies and epigenetic effects of reduced mobility on limb development have also been studied for anurans (Abdala and Ponssa, ; Abdala et al., ).…”

“…Studies related to evolutionary novelties or losses include evolution of transparent eyelids in lizards (Guerra‐Fuentes et al., ), evolution of jaw abductor muscles, tooth variation, and limblessness in snakes (Zaher, ; Zaher and Prudente, ; Zaher and Rieppel, ; Apesteguía and Zaher ; Zaher et al., ), evolution of limb bone elements in turtles (Fabrezi et al., ), or loss of digits and limb reduction in gymnophthalmid lizards (Roscito and Rodrigues, ; Roscito et al., ). Separate but often complementary lines of research take advantage of the growing wealth of genomic data to explore the molecular evolution of different gene families and their role in morphological and physiological adaptation, such as evolution of Hox genes and the origins of limbless morphologies in amphibians and reptiles (Singarete et al., ), origin and evolvability in PAX genes involved in embryonic development and organogenesis (Paixao‐Cortes et al., , ), nonvertebrate origins of retinoic acid involved in vertebrate development and homeostasis (Simoes‐Costa et al., ), genes involved in olfactory behaviors (Lavagnino et al., ) or in hybrid incompatibility (Mensch et al., ) in flies, hemoglobin diversification in teleost fish (Opazo et al., ), and comparative genomics of cetaceans (Nery et al., ).…”