Evolutionary changes of Hox genes and relevant regulatory factors provide novel insights into mammalian morphological modifications.

The diversity of body plans of mammals accelerates the innovation of lifestyles and the extensive adaptation to different habitats, including terrestrial, aerial and aquatic habitats. However, the genetic basis of those phenotypic modifications, which have occurred during mammalian evolution, remains poorly explored. In the present study, we synthetically surveyed the evolutionary pattern of Hox clusters that played a powerful role in the morphogenesis along the head-tail axis of animal embryos and the main regulatory factors (Mll, Bmi1 and E2f6) that control the expression of Hox genes. A deflected density of repetitive elements and lineage-specific radical mutations of Mll have been determined in marine mammals with morphological changes, suggesting that evolutionary changes may alter Hox gene expression in these lineages, leading to the morphological modification of these lineages. Although no positive selection was detected at certain ancestor nodes of lineages, the increased ω values of Hox genes implied the relaxation of functional constraints of these genes during the mammalian evolutionary process. More importantly, 49 positively-selected sites were identified in mammalian lineages with phenotypic modifications, indicating adaptive evolution acting on Hox genes and regulatory factors. In addition, 3 parallel amino acid substitutions in some Hox genes were examined in marine mammals, which might be responsible for their streamlined body.

Cite this article as:

Li K, Sun X, Chen M et al. (2018). Evolutionary changes of Hox genes and relevant regulatory factors provide novel insights into mammalian morphological modifications. Integrative Zoology 13, 21–35.

Additional supporting information may be found in the online version of this article.

Table S1 Ensembl transcript IDs, GenBank accession numbers and genomic location information of all Hox genes and relevant regulatory factors used in the present research

Table S2 Lineage‐specific amino acids changes in regulatory factors and Hox genes among mammals

Table S3 Parameter estimates under branch models among Hox genes and regulatory factors.

Table S4 The parameters of selective pressure for Hox genes and E2f6 among mammals by branch‐site models

Table S5 Positively selected sites and quality changes in Hox genes and regulatory factors among mammals

Figure S1 The proportion of repetitive elements numbers to total repeats in different gene regions among species

Figure S2 3‐D structure distribution of positively selected sites (red balls) and lineage‐specific radical amino acids change sites (brown balls) in corresponding proteins. The homeodomain of Hox proteins, DNA binding region of E2f6, and transcriptional activation region of Mll are colored yellow. N‐terminal and C‐terminal regions are ocean blue and violet, respectively.

Supporting Information

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