Evolution of the human-specific microRNA miR-941
Hai Yang Hu, Liu He, Kseniya Fominykh, Zheng Yan, Song Guo, Xiaoyu Zhang, Martin S. Taylor, Lin Tang, Jie Li, Jianmei Liu, Wen Wang, Haijing Yu & Philipp Khaitovich
AffiliationsContributionsCorresponding authors
Nature Communications 3, Article number: 1145 doi:10.1038/ncomms2146
Received 15 February 2012 Accepted 20 September 2012 Published 23 October 2012
Abstract
MicroRNA-mediated gene regulation is important in many physiological processes. Here we explore the roles of a microRNA, miR-941, in human evolution. We find that miR-941 emerged de novo in the human lineage, between six and one million years ago, from an evolutionarily volatile tandem repeat sequence. Its copy-number remains polymorphic in humans and shows a trend for decreasing copy-number with migration out of Africa. Emergence of miR-941 was accompanied by accelerated loss of miR-941-binding sites, presumably to escape regulation. We further show that miR-941 is highly expressed in pluripotent cells, repressed upon differentiation and preferentially targets genes in hedgehog- and insulin-signalling pathways, thus suggesting roles in cellular differentiation. Human-specific effects of miR-941 regulation are detectable in the brain and affect genes involved in neurotransmitter signalling. Taken together, these results implicate miR-941 in human evolution, and provide an example of rapid regulatory evolution in the human linage.