Adaptive tail-length evolution in deer mice is associated with differential Hoxd13 expression in early development

Abstract

Variation in the size and number of axial segments underlies much of the diversity in animal body plans. Here, we investigate the evolutionary, genetic, and developmental mechanisms driving tail-length differences between forest and prairie ecotypes of deer mice (Peromyscus maniculatus). We first show that long-tailed forest mice perform better in an arboreal locomotion assay, consistent with tails being important for balance during climbing. The long tails of these forest mice consist of both longer and more caudal vertebrae than prairie mice. Using quantitative genetics, we identify six genomic regions that contribute to differences in total tail length, three of which associate with vertebra length and the other three with vertebra number. For all six loci, the forest allele increases tail length, consistent with the cumulative effect of natural selection. Two of the genomic regions associated with variation in vertebra number contain Hox gene clusters. Of those, we find an allele-specific decrease in Hoxd13 expression in the embryonic tail bud of long-tailed forest mice, consistent with its role in axial elongation. Additionally, we find that forest embryos have more presomitic mesoderm than prairie embryos, and that this correlates with an increase in the number of neuromesodermal progenitors (NMPs), which are modulated by Hox13 paralogs. Together, these results suggest a role for Hoxd13 in the development of natural variation in adaptive morphology on a microevolutionary timescale.

The roles of isolation and interspecific interaction in generating the functional diversity of an insular mammal radiation

“…The traits with the highest within-clade variance — δ 15 N, tail length, body size — are all thought to be evolutionarily labile. Changes in tail length, body size, and intestinal tract morphology can occur on brief evolutionary time scales (Powell and King 1997, Naya et al 2008, Kingsley et al 2017, 2021), whereas morphological changes in cranial shape, such as substantial rostral elongation and the reduction of molar grinding area, may take much longer. Indeed, insular species are known to have rapidly expanded breadths of diet and labile morphological traits following colonization (Stuart et al 2014) and subsequent speciation (Wilson 1959, 1961, Lister 1976, Rowe et al 2016a).…”

CTCF-DEPENDENT INSULATION OFHoxb13AND THE HETEROCHRONIC CONTROL OF TAIL LENGTH

“…The body axis of most mammalian species including humans (1) terminates with a tail of a defined and characteristic length. Since the isolation of the T/Brachyury gene (2), several genetic determinants of tail variation have been described and progresses have been made in exploring the mechanisms of length variability either during development (3), in wild mouse populations (4) or during human evolution (5). In this context, several studies reported a role for the most posterior Hox13 genes in setting up tail length (4,6) and a genetic modification in mice (7) produced tail overgrowth reminiscent of the targeted inactivation of Hoxb13 (8,9).…”

“…Since the isolation of the T/Brachyury gene (2), several genetic determinants of tail variation have been described and progresses have been made in exploring the mechanisms of length variability either during development (3), in wild mouse populations (4) or during human evolution (5). In this context, several studies reported a role for the most posterior Hox13 genes in setting up tail length (4,6) and a genetic modification in mice (7) produced tail overgrowth reminiscent of the targeted inactivation of Hoxb13 (8,9). Conversely, forced expression of either Hoxb13 or of other group 13 genes induced variable, often dramatic vertebral column truncations (10).…”

“…As a consequence, it was proposed that Hox13 genes were collectively responsible for terminating the extension of the main body axis during embryogenesis (10)(11)(12), thereby setting the length of the tail through a dominant negative effect of their protein products (13). Recent results obtained using unbiased approaches in natural populations of either deer mice (4), or Chinese long-tailed sheep breeds (14) have further identified Hoxd13 and Hoxb13 as candidate genes to regulate tail length.…”