Young genes have distinct gene structure, epigenetic profiles, and transcriptional regulation

Abstract

Species-specific, new, or "orphan" genes account for 10%-30% of eukaryotic genomes. Although initially considered to have limited function, an increasing number of orphan genes have been shown to provide important phenotypic innovation. How new genes acquire regulatory sequences for proper temporal and spatial expression is unknown. Orphan gene regulation may rely in part on origination in open chromatin adjacent to preexisting promoters, although this has not yet been assessed by genome-wide analysis of chromatin states. Here, we combine taxon-rich nematode phylogenies with Iso-Seq, RNA-seq, ChIP-seq, and ATAC-seq to identify the gene structure and epigenetic signature of orphan genes in the satellite model nematode Consistent with previous findings, we find young genes are shorter, contain fewer exons, and are on average less strongly expressed than older genes. However, the subset of orphan genes that are expressed exhibit distinct chromatin states from similarly expressed conserved genes. Orphan gene transcription is determined by a lack of repressive histone modifications, confirming long-held hypotheses that open chromatin is important for new gene formation. Yet orphan gene start sites more closely resemble enhancers defined by H3K4me1, H3K27ac, and ATAC-seq peaks, in contrast to conserved genes that exhibit traditional promoters defined by H3K4me3 and H3K27ac. Although the majority of orphan genes are located on chromosome arms that contain high recombination rates and repressive histone marks, strongly expressed orphan genes are more randomly distributed. Our results support a model of new gene origination by rare integration into open chromatin near enhancers.

Enhancers facilitate the birth of de novo genes and their integration into regulatory networks

“…Our study provides empirical support for the hypothesis that enhancers may facilitate de novo gene evolution, which to our knowledge was first proposed upon the discovery of enhancer RNA (Kim, et al 2010) and later expanded upon in a perspective piece by Wu and Sharp (Wu and Sharp 2013). Our findings complement recent work on the regulatory architecture of the nematode Pristionchus pacificus, which showed that young genes – those private to P. pacificus – are in closer proximity to enhancers than genes with one-to-one orthologs in other nematode species (Werner, et al 2018). The observation that many young ORFs are proximal to enhancers in both nematodes and mammals suggests that this mode of gene evolution dates back to at least the common ancestor of Bilateria, and possibly even earlier, since cnidarians, ctenophores, and sponges also employ distal regulatory elements (Schwaiger, et al 2014; Gaiti, et al 2017; Sebé-Pedrós, et al 2018; Sebé-Pedrós, et al 2018).…”

“…S1 shows that these trends are not driven by exon length). Taken together, these results support a model in which enhancers facilitate the expression of young ORFs (Wu and Sharp 2013; Werner, et al 2018).…”

“…The first evidence that enhancers can facilitate de novo gene birth was recently provided using whole-animal transcriptomic and epigenetic data from the nematode Pristionchus pacificus (Werner, et al 2018). Specifically, the transcription start sites of expressed genes that were in open chromatin and private to P. pacificus were found to be in closer proximity to histone modifications indicative of enhancers than the transcription start sites of expressed genes that were in open chromatin and shared with other nematode species.…”

Selection following gene duplication shapes recent genome evolution in the pea aphid Acyrthosiphon pisum

“…This shows that the chromatin states of promoters of simple duplicated genes can evolve independently in each pair. This could correspond to the differential chromatin states recently identified in new genes in nematodes (Werner et al 2018), since in each pair, one gene is more recent than the other.…”

Evolution of neuronal anatomy and circuitry in two highly divergent nematode species

“…The species shared their last common ancestor around 100 million years ago, which is longer than the human-mouse separation (nei and Glazko, 2001;Prabh et al, 2018;Rota-Stabelli et al, 2013;Werner et al, 2018), and have since diverged to populate very discrete habitats and engage in distinct sets of behaviors. C. elegans is a free-living nematode that can mainly be found in rotten fruit while members of the genus Pristionchus are regularly found in association with several species of scarab beetles {Herrmann 2006b; Herrmann 2007, (Koneru et al, 2016;Ragsdale, 2015).…”