| First Author | Xia B | Year | 2024 |
| Journal | Nature | Volume | 626 |
| Issue | 8001 | Pages | 1042-1048 |
| PubMed ID | 38418917 | Mgi Jnum | J:345828 |
| Mgi Id | MGI:7611785 | Doi | 10.1038/s41586-024-07095-8 |
| Citation | Xia B, et al. (2024) On the genetic basis of tail-loss evolution in humans and apes. Nature 626(8001):1042-1048 |
| abstractText | The loss of the tail is among the most notable anatomical changes to have occurred along the evolutionary lineage leading to humans and to the 'anthropomorphous apes'(1-3), with a proposed role in contributing to human bipedalism(4-6). 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(7-9)-pairs with a neighbouring 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 Tbxt, mimicking the expression pattern of its hominoid orthologue TBXT. Mice expressing both Tbxt isoforms 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. These results support the notion that the exon-skipped transcript is sufficient to induce a tail-loss phenotype. Moreover, mice expressing the exon-skipped Tbxt isoform develop neural tube defects, a condition that affects approximately 1 in 1,000 neonates in humans(10). 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. |
