Evolutionary and functional genomics of DNA methylation in maize domestication and improvement

DNA methylation is a ubiquitous chromatin feature — in maize, more than 25% of cytosines in the genome are methylated. Recently, major progress has been made in describing the molecular mechanisms driving methylation, yet variation and evolution of the methylation landscape during maize domestication remain largely unknown. Here we leveraged whole-genome sequencing (WGS) and whole-genome bisulfite sequencing (WGBS) on populations of modern maize, landrace, and teosinte (Zea mays ssp. parviglumis) to investigate the adaptive and phenotypic consequences of methylation variations in maize. By using a novel estimation approach, we inferred the methylome site frequency spectrum (mSFS) to estimate forward and backward methylation mutation rates and selection coefficients. We only found weak evidence for direct selection on DNA methylation in any context, but thousands of differentially methylated regions (DMRs) were identified in population-wide that are correlated with recent selection. Further investigation revealed that DMRs are enriched in 5’ untranslated regions, and that maize hypomethylated DMRs likely helped rewire distal gene regulation. For two trait-associated DMRs, vgt1-DMR and tb1DMR, our HiChIP data indicated that the interactive loops between DMRs and respective downstream genes were present in B73, a modern maize line, but absent in teosinte. Functional analyses suggested that these DMRs likely served as cis-acting elements that modulated gene regulation after domestication. Our results enable a better understanding of the evolutionary forces acting on patterns of DNA methylation and suggest a role of methylation variation in adaptive evolution. We collected whole-genome sequencing and bisulfite sequencing data of 51 samples, including the wild ancestor of maize — teosinte (Zea mays ssp. parviglumis, N=20), Mexican landraces (N=17),and modern maize inbred lines (N=14) to understand the impact of epigenetics on maize domestication. The "modern maize inbred lines (N=14)" were downloaded from NCBI. The descriptive details for all 51 samples are in supplementary file metadata_51samples.xls.