title: Evolution of the human-specific microRNA miR-941.
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.
authors.affiliation: CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, 320 Yue Yang Road, Shanghai 200031, China.
authors.forename: Hai Yang
authors.initials: HY
authors.lastname: Hu
authors.forename: Liu
authors.initials: L
authors.lastname: He
authors.forename: Kseniya
authors.initials: K
authors.lastname: Fominykh
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yan
authors.forename: Song
authors.initials: S
authors.lastname: Guo
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhang
authors.forename: Martin S
authors.initials: MS
authors.lastname: Taylor
authors.forename: Lin
authors.initials: L
authors.lastname: Tang
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Jianmei
authors.initials: J
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.forename: Haijing
authors.initials: H
authors.lastname: Yu
authors.forename: Philipp
authors.initials: P
authors.lastname: Khaitovich
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D018628:Gene Dosage / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008253:Macaca mulatta; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D002679:Pan troglodytes; D039904:Pluripotent Stem Cells / Q000378:metabolism; D020080:Tandem Repeat Sequences / Q000235:genetics
chemical_list: C581560:MIRN941 microRNA, human; D035683:MicroRNAs