Young genes have distinct gene structure, epigenetic profiles, and transcription start site regulation

Species-specific, new, or 'orphan' genes account for 10-30% of eukaryotic genomes. Despite initially considered to be non-functional, 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 pre-existing 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 Pristionchus pacificus. Consistent with previous findings we find young genes are shorter, contain fewer exons, and are on average less expressed than older genes. Surprisingly 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. While the majority of orphan genes are located on chromosome arms that contain high recombination rates and repressive histone marks, expressed orphan genes are more randomly distributed. Our results support a model of new gene origination by rare integration into open chromatin near enhancers.