With massive genome sequencing across the tree of life, we are in an era in which it becomes possible to pinpoint the specific genetic changes underlying key evolutionary traits. Human evolutionary genetics is not only about the human genome. We look broadly to the genomes of apes, primates, mammals, vertebrates, and even invertebrates, and apply systems genetics and comparative genomic approaches to identify DNA variants associated with traits across the major milestones of human evolution. We combine synthetic biology and developmental genetics approaches to understand the genetic and molecular mechanisms underlying human evolution, and how these evolutionary changes impact modern human development and health. 

The loss of the tail is one of the main anatomical evolutionary changes to have occurred along the lineage leading to humans and the “anthropomorphous apes”. This morphological reprogramming in the ancestral hominoids has been long considered to have accommodated a characteristic style of locomotion and contributed to the evolution of bipedalism in humans. Yet, the genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown. We recently presented evidence that tail-loss evolution was mediated by the insertion of an individual Alu element into the genome of the hominoid ancestor. This study opens doors to many more exciting questions to study:

• How tail-loss was selected along the hominoid lineage? We hypothesize that tail-loss marks an important evolutionary milestone by facilitating the locomotion evolution in hominoids, and eventually contributing to the bipedal locomotion in hominins. We are developing animal models and coupling molecular and genomic approaches to answer this question.

• How does the genetics underlying tail-loss affect modern human development and health? We hypothesized that the underlying genetics was associated with an evolutionary trade-off that may continue to affect human health today.

The testis expresses the largest number of genes of any mammalian organ, a finding that has long puzzled molecular biologists. We recently presented evidence that this widespread transcription maintains DNA sequence integrity in the male germline by correcting DNA damage through a mechanism we term transcriptional scanning. We find that genes expressed during spermatogenesis display lower mutation rates on the transcribed strand and have low diversity in the population. Moreover, this effect is fine-tuned by the level of gene expression during spermatogenesis. The unexpressed genes, which in our model do not benefit from transcriptional scanning, diverge faster over evolutionary time scales and are enriched for sensory and immune-defense functions. Collectively, we propose that transcriptional scanning shapes germline mutation signatures and modulates mutation rates in a gene-specific manner, maintaining sequence integrity for the bulk of genes but allowing for faster evolution in a specific subset.