Transposable element exaptation is the primary source of novelty in the primate gene regulatory landscape

Abstract

16Gene regulation plays a critical role in the evolution of phenotypic diversity. We investigated 17 the evolution of liver promoters and enhancers in six primate species. We performed ChIP-18 seq for two histone modifications and RNA-seq to profile cis-regulatory element (CRE) 19 activity and gene expression. The primate regulatory landscape is largely conserved across 20 the lineage. Conserved CRE function is associated with sequence conservation, proximity 21 to coding genes, cell type specificity of CRE function, and transcription factor binding. 22 Newly evolved CREs are enriched in immune response and neurodevelopmental functions, 23 while conserved CREs bind master regulators. Transposable elements (TEs) are the 24 primary source of novelty in primate gene regulation. Newly evolved CREs are enriched in 25 young TEs that affect gene expression. However, only 17% of conserved CREs overlap a 26 TE, suggesting that target gene expression is under strong selection. Finally, we identified 27 specific genomic features driving the functional recruitment of newly inserted TEs. 28 29 30 56 With a goal of answering these questions, we collected liver samples from six 57 primate species. Core liver functions are largely conserved across primate species. 58 However, different environmental exposures, diets, and lifestyles likely directed the 59 adaptation of liver functions, and associated regulatory evolution, making this tissue an 60 optimal model in which explore the conservation and divergence of the gene regulation. 61 To characterize primate liver cis-regulatory evolution, we performed chromatin 62 immunoprecipitation followed by sequencing (ChIP-seq) for Histone H3 Lysine 27 63 89 90 91 Results 92 93Data generation, quality assessment, and validation 94 We generated a total of 757 million RNA-seq reads and 1.70 billion ChIP-seq reads 95 (H3K27ac, H3K4me1, and input) from post mortem livers of three or four individuals per 96 3 species of mouse lemur (Microcebus murinus), bushbaby (Otolemur garnettii), marmoset 97 (Callithrix jacchus), rhesus macaque (Macaca mulatta), chimpanzee (Pan troglodytes), and 98

Transposable Element Exaptation into Regulatory Regions Is Rare, Influenced by Evolutionary Age, and Subject to Pleiotropic Constraints

“…In this paper, we demonstrate that, even though TEs play important roles in remodeling regulatory networks and enabling functional innovation (Lynch et al 2011(Lynch et al , 2015Chuong 2013;Chuong et al 2016a;Trizzino et al 2016), they are depleted for regulatory activity compared with their prevalence across the human and mouse genomes. This should not be…”

Transposable elements as a potent source of diverse cis -regulatory sequences in mammalian genomes

“…Contributions of TEs to regulatory landscapes are particularly pronounced when species-specific enhancers are considered, including through waves of repeat expansions [12]. For example, the majority of ape-specific and human-specific liver enhancers overlap TEs (77% of ape-specific enhancers compared with 16% of evolutionarily conserved enhancers) [50]. Quantitative comparisons of enhancer landscapes between chimpanzee and human cranial neural crest cells (CNCCs) showed that speciesspecific changes in enhancer activity can be explained by the underlying regulatory sequence divergence and is linked to expression differences in genes involved in development of craniofacial structures [51].…”

Specific subfamilies of transposable elements contribute to different domains of T lymphocyte enhancers

“…A growing body of evidence suggests that specific TE subfamilies have been coopted for transcriptional regulation in a number of biological contexts (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). In particular, TEassociated enhancers contributed to the evolution of early development (17), placentation (18), mammalian pregnancy (14),…”