TBXT
How Humans Lost Their Tails
Hominoids – which include humans and the apes – are distinct among the primates in their loss of an external tail. The loss of the tail is inferred to have occurred ~25 million years ago when the hominoid lineage diverged from the ancient Old World monkeys, leaving only 3-4 caudal vertebrae to form the coccyx, or tailbone, in modern humans. It has long been speculated that tail loss in hominoids has contributed to bipedal locomotion, whose evolutionary occurrence coincided with the loss of tail. Yet, the precise genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown.
The recent primate genome sequencing projects have made possible the identification of causal links between genotypic and phenotypic changes, and enable the search for hominoid-specific genetic elements controlling tail development. In this project, we found evidence that tail-loss evolution was mediated by the insertion of an individual Alu element into the genome of the hominoid ancestor. We demonstrate that this Alu element – inserted into an intron of the TBXT gene (also called T or Brachyury) – pairs with a neighboring ancestral Alu element encoded in the reverse genomic orientation and leads to a hominoid-specific alternative splicing event. Yet the exact evolutionary advantage that drove the selection for the loss of the tail along the hominoid lineage is unclear, we propose that such selection was associated with an adaptive cost of potential neural tube defects and that this ancient evolutionary trade-off may thus continue to affect human health today.
Read more about the tail-loss evolution in hominoids in Xia et al., Nature 2024, as well as in The New York Times and Science News.
IN COLLABORATION WITH:
Bo Xia, previously at the Institute for Computational Medicine at NYU Langone Health; now at Harvard.
Itai Yanai, PhD, Institute for Computational Medicine at NYU Langone Health