Noncoding origins of anthropoid traits and a new null model of transposon functionalization

Abstract

Little is known about novel genetic elements that drove the emergence of anthropoid primates. We exploited the sequencing of the marmoset genome to identify 23,849 anthropoid-specific constrained (ASC) regions and confirmed their robust functional signatures. Of the ASC base pairs, 99.7% were noncoding, suggesting that novel anthropoid functional elements were overwhelmingly cis-regulatory. ASCs were highly enriched in loci associated with fetal brain development, motor coordination, neurotransmission, and vision, thus providing a large set of candidate elements for exploring the molecular basis of hallmark primate traits. We validated ASC192 as a primate-specific enhancer in proliferative zones of the developing brain. Unexpectedly, transposable elements (TEs) contributed to >56% of ASCs, and almost all TE families showed functional potential similar to that of nonrepetitive DNA. Three L1PA repeat-derived ASCs displayed coherent eye-enhancer function, thus demonstrating that the ''gene-battery'' model of TE functionalization applies to enhancers in vivo. Our study provides fundamental insights into genome evolution and the origins of anthropoid phenotypes and supports an elegantly simple new null model of TE exaptation.

Dynamic Transcription of Distinct Classes of Endogenous Retroviral Elements Marks Specific Populations of Early Human Embryonic Cells

“…ERVs are a major source of genetic innovation and can generate primate-specific regulatory sites that act as enhancers or transcription start sites of nearby genes (del Rosario et al, 2014;Faulkner et al, 2009;Feschotte and Gilbert, 2012;Jacques et al, 2013;Kunarso et al, 2010;Rebollo et al, 2012). Here, we show that the regulatory elements of ERVs systematically control their own stage-specific expression in human embryos.…”

Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters

“…The LacZ reporter clones were constructed as previously described (del Rosario et al 2014). PCR fragments corresponding to tested regions were cloned into the pENTR plasmid (Invitrogen) and transferred into the Gateway-compatible hsp68-LacZ reporter vector using LR recombination.…”

Transposable elements are the primary source of novelty in primate gene regulation

“…Although previous studies have suggested a role for transposable elements (TEs) in the evolution of gene regulation, validating the functional contribution of TEs in mammalian gene regulation remains a challenge (McClintock 1950(McClintock , 1984Britten and Davidson 1969;Davidson and Britten 1979;Jordan et al 2003;Bejerano et al 2006;Wang et al 2007;Bourque et al 2008;Sasaki et al 2008;Markljung et al 2009;Kunarso et al 2010;Lynch et al 2011Lynch et al , 2015Schmidt et al 2012;Chuong et al 2013Chuong et al , 2016Jacques et al 2013;Xie et al 2013;del Rosario et al 2014;Sundaram et al 2014;Du et al 2016;Rayan et al 2016;Ward et al 2017).…”