Edited by Michael Lynch, The Biodesign Institute, Tempe, AZ, and approved July 24, 2018 (received for review February 22, 2018)
Nucleosomal modifications have been implicated in fundamental epigenetic regulation, whereas the roles of nucleosome binding in shaping changes through evolution remain to be addressed. Here we performed a comparative study to clarify the roles of nucleosome occupancy in exon origination. By profiling a high-resolution, cross-species mononucleosome landscape for mammalian tissues, we found nucleosome occupancy profiles are conserved across tissues and species. Further, through a phylogenetic approach, we found that the feature of differential nucleosome occupancy appears prior to the origination of new exons and, presumably, facilitates the origin of new exons by increasing the splice strength of the ancestral nonexonic regions through driving a local difference in GC content, which suggests the function of nucleosome binding in exonization.
Nucleosomal modifications have been implicated in fundamental epigenetic regulation, but the roles of nucleosome occupancy in shaping changes through evolution remain to be addressed. Here we present high-resolution nucleosome occupancy profiles for multiple tissues derived from human, macaque, tree shrew, mouse, and pig. Genome-wide comparison reveals conserved nucleosome occupancy profiles across both different species and tissue types. Notably, we found significantly higher levels of nucleosome occupancy in exons than in introns, a pattern correlated with the different exon–intron GC content. We then determined whether this biased occupancy may play roles in the origination of new exons through evolution, rather than being a downstream effect of exonization, through a comparative approach to sequentially trace the order of the exonization and biased nucleosome binding. By identifying recently evolved exons in human but not in macaque using matched RNA sequencing, we found that higher exonic nucleosome occupancy also existed in macaque regions orthologous to these exons. Presumably, such biased nucleosome occupancy facilitates the origination of new exons by increasing the splice strength of the ancestral nonexonic regions through driving a local difference in GC content. These data thus support a model that sites bound by nucleosomes are more likely to evolve into exons, which we term the “nucleosome-first” model.
↵1Y.L. and C.L. contributed equally to this work.
Author contributions: A.H. and C.-Y.L. designed research; Y.L., C.L., S.L., Q.P., and N.A.A. performed research; Y.L., S.L., and Q.P. analyzed data; and Y.L. and C.-Y.L. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The MNase-seq and RNA-seq data in this study are available in the Gene Expression Omnibus (accession no. GSE106580).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1802561115/-/DCSupplemental.
This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
