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

Abstract

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.

Homeobox C8 inhibited the osteo‐/dentinogenic differentiation and migration ability of stem cells of the apical papilla via activating KDM1A

“…Genes belonging to the HOXA and HOXD families are important for the outgrowth and patterning of the limb (He, Nakada, & Morrison, 2009; Mallo, 2018). HOXB genes are involved in the differentiation of the hematopoietic progenitor cells, the homeotic transformation of the cervical vertebra, and defects in the closure of sternal rudiments in mice (Collins & Thompson, 2018; Li et al, 2018). The Deletion of HOXC genes results in lower extremity malformations (Alvarado, McCall, Hecht, Dobbs, & Gurnett, 2016).…”

Accelerated Evolution of Limb-Related Gene Hoxd11 in the Common Ancestor of Cetaceans and Ruminants (Cetruminantia)

“…Abbreviations for taxonomy are "Pe" (Perissodactyla), "Ca" (Carnivora), "Ch" (Chiroptera), "La" (Lagomorpha) and "Af" (Afrosoricida). further evidences that different Hox genes are important for the diversified morphologies during mammalian evolution (Liang et al 2013;Nery et al 2016;Li et al 2018). Considering that Hoxd11 is more specifically involved in carpal and tarsal bone development (Davis and Capecchi 1994;Koyama et al 2010), we conducted a molecular evolutionary study of this gene to determine whether evolution of Hoxd11 might explain the bone number variations in Cetruminantia.…”