Adaptive Evolution of the Hox Gene Family for Development in Bats and Dolphins

Abstract

Bats and cetaceans (i.e., whales, dolphins, porpoises) are two kinds of mammals with unique locomotive styles and occupy novel niches. Bats are the only mammals capable of sustained flight in the sky, while cetaceans have returned to the aquatic environment and are specialized for swimming. Associated with these novel adaptations to their environment, various development changes have occurred to their body plans and associated structures. Given the importance of Hox genes in many aspects of embryonic development, we conducted an analysis of the coding regions of all Hox gene family members from bats (represented by Pteropus vampyrus, Pteropus alecto, Myotis lucifugus and Myotis davidii) and cetaceans (represented by Tursiops truncatus) for adaptive evolution using the available draft genome sequences. Differences in the selective pressures acting on many Hox genes in bats and cetaceans were found compared to other mammals. Positive selection, however, was not found to act on any of the Hox genes in the common ancestor of bats and only upon Hoxb9 in cetaceans. PCR amplification data from additional bat and cetacean species, and application of the branch-site test 2, showed that the Hoxb2 gene within bats had significant evidence of positive selection. Thus, our study, with genomic and newly sequenced Hox genes, identifies two candidate Hox genes that may be closely linked with developmental changes in bats and cetaceans, such as those associated with the pancreatic, neuronal, thymus shape and forelimb. In addition, the difference in our results from the genome-wide scan and newly sequenced data reveals that great care must be taken in interpreting results from draft genome data from a limited number of species, and deep genetic sampling of a particular clade is a powerful tool for generating complementary data to address this limitation.

Unique expression patterns of multiple key genes associated with the evolution of mammalian flight

“…Because 5 0 HoxD genes can induce Shh expression in limbs [23,33], we propose that the short-term re-initiation of Shh expression in bat wing is caused by the significantly high expression of 5 0 HoxD genes at stages 15-16, especially the transient elevation in the expression dose of Hoxd10 and Hoxd11 at stage 15. Our previous study and Liang et al did not find positive selection acting on the coding sequences of any 5 0 HoxD genes in the common ancestor of bats, suggesting that functions of these genes are important and conserved [34,35]. Our finding of prolonged and high expression of 5 0 HoxD genes in bat wings suggests a strong positive selection acted on enhancers to alter their expression patterns during wing formation in bat ancestors.…”

Minke whale genome and aquatic adaptation in cetaceans

“…38). Additionally, several HOX genes ( HOXA5, HOXB1, HOXB2, HOXB5, HOXD12 and HOXD13 ), which have an important role in the body plan and embryonic development 28 , were positively selected in the whale lineage compared to terrestrial mammals, reflecting the morphological adaptation of the whale to the aquatic environment (Supplementary Fig. 39 and Supplementary Note).…”

Molecular adaptation of the CREB-Binding Protein for aquatic living in cetaceans

“…The phylogenetic tree of the species (Figure 1) used as a guide tree was generated using an iTOL web server [10] and derived from previous study [11]. A PRANK program was applied for multiple sequence alignment for the coding sequences of the 19 mammals [9].…”

“…As the program was initially devised for detecting mutations in human genes, the functional effect of each variation is classified as "probably damaging", "possibly damaging", or "benign". The ω values of CREBBP genes in distinct evolutionary lineages of cetaceans and other mammals using a phylogenetic tree derived from Liang et al [11]. The cetacean branch (red colored) was used as foreground branch shown in Table 2.…”