On the genetic basis of tail-loss evolution in humans and apes [Capture-seq]

ABSTRACT: The loss of the tail is among the notable anatomical changes to have occurred along the evolutionary lineage leading to humans and to the “anthropomorphous apes”, with a hypothesized role in contributing to human bipedalism. Yet, the genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown. Here, we present evidence that an individual insertion of an Alu element in the genome of the hominoid ancestor may have contributed to tail-loss evolution. We demonstrate that this Alu element – inserted into an intron of the TBXT gene – pairs with a neighboring ancestral Alu element encoded in the reverse genomic orientation and leads to a hominoid-specific alternative splicing event. To study the effect of this splicing event, we generated multiple mouse models that express both full-length and exon-skipped isoforms of mouse Tbxt, mimicking the expression pattern of its hominoid ortholog TBXT. We found that mice expressing both Tbxt isoforms can exhibit a complete absence of the tail or a shortened tail, depending on the relative abundance of Tbxt isoforms expressed at the embryonic tail bud, supporting the notion that the exon-skipped transcript is sufficient to induce a tail-loss phenotype. We further noted that mice expressing the exon-skipped Tbxt isoform may develop neural tube defects, a condition that affects ~1/1,000 neonates in human. Thus tail-loss evolution may have been associated with an adaptive cost of the potential for neural tube defects, which continue to affect human health today.

ORGANISM(S): Mus musculus

PROVIDER: GSE252278 | GEO | 2024/01/01

REPOSITORIES: GEO