Accelerated evolution in the human lineage led to gain and loss of transcriptional enhancers in the RBFOX1 locus | Science Advances
Abstract
A long-standing goal of evolutionary biology is to decode how changes in gene regulatory networks contribute to human-specific traits. Human accelerated regions (HARs) are prime candidates for driving gene regulatory modifications in human development. The
RBFOX1
locus is densely populated with HARs, providing a set of potential regulatory elements that could have changed its expression in the human lineage. Here, we examined the role of
RBFOX1
-HARs using transgenic zebrafish reporter assays and identified 15 transcriptional enhancers that are active in the developing nervous system, 9 of which displayed differential activity between the human and chimpanzee sequences. The engineered loss of two selected
RBFOX1
-HARs in knockout mouse models modified
Rbfox1
expression at specific developmental stages and tissues in the brain, influencing the expression and splicing of a high number of
Rbfox1
target genes. Our results provided insight into the spatial and temporal changes in gene expression driven by
RBFOX1
-HARs.