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.

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“…4). The Primate and Homo sapience oncogenic miRNAs have retained their harmful regulatory interaction with target genes through their evolution because miRNA-mRNA interaction pave the way for the loss of newly formed miRNA and or causes the elimination of detrimental miRNA binding sites [16,26,27,28]. The expression of miR-195 and miR-497 were highly conserved in miRNA cluster and located at chromosome 17p13.1 and were down-regulated by DNA methylation and increased CpG methylation in breast cancer [29].…”

Human MicroRNA-548p Decreases Hepatic Apolipoprotein B Secretion and Lipid Synthesis

“…The conservation allows an easy way to evaluate physiological effects of overexpression or loss-of-function of specific miRs in model organisms before human studies. Nevertheless, many human or primate specific miRs have been identified that play important roles in physiological and pathological pathways, such as cellular differentiation and cancer development (55–57). It is likely that primate miRs have evolved to regulate species specific phenotypes.…”

Genome‐wide identification, expression profiling, and target gene analysis of microRNAs in the Onion thrips, Thrips tabaci Lindeman (Thysanoptera: Thripidae), vectors of tospoviruses (Bunyaviridae)

“…High‐throughput next‐generation sequencing (NGS) emerged as a powerful tool to identify miRNAs from animals and plants (Calla & Geib, 2015; Guillem, Bastian, Maria‐Dolors, & Xavier, 2016; Nandety, Sharif, Kamita, Ramasamy, & Falk, 2015; Song et al., 2011; Wang et al., 2012; Wu et al., 2013). It has accelerated the pace of miRNA discovery from various animals and plants (Avesson, Reimegard, Wagner, & Söderbom, 2012; Burnside et al., 2008; Ge et al., 2013; Hu et al., 2012; Kang et al., 2012; Koh et al., 2010; Zhang et al., 2012). …”