Wang Jun, Marowsky Nicholas C, Fan Chuanzhu
Department of Biological Sciences, Wayne State University, Detroit, Michigan, United States of America.
PLoS One. 2014 Oct 13;9(10):e110357. doi: 10.1371/journal.pone.0110357. eCollection 2014.
It has been shown that gene body DNA methylation is associated with gene expression. However, whether and how deviation of gene body DNA methylation between duplicate genes can influence their divergence remains largely unexplored. Here, we aim to elucidate the potential role of gene body DNA methylation in the fate of duplicate genes. We identified paralogous gene pairs from Arabidopsis and rice (Oryza sativa ssp. japonica) genomes and reprocessed their single-base resolution methylome data. We show that methylation in paralogous genes nonlinearly correlates with several gene properties including exon number/gene length, expression level and mutation rate. Further, we demonstrated that divergence of methylation level and pattern in paralogs indeed positively correlate with their sequence and expression divergences. This result held even after controlling for other confounding factors known to influence the divergence of paralogs. We observed that methylation level divergence might be more relevant to the expression divergence of paralogs than methylation pattern divergence. Finally, we explored the mechanisms that might give rise to the divergence of gene body methylation in paralogs. We found that exonic methylation divergence more closely correlates with expression divergence than intronic methylation divergence. We show that genomic environments (e.g., flanked by transposable elements and repetitive sequences) of paralogs generated by various duplication mechanisms are associated with the methylation divergence of paralogs. Overall, our results suggest that the changes in gene body DNA methylation could provide another avenue for duplicate genes to develop differential expression patterns and undergo different evolutionary fates in plant genomes.
已有研究表明，基因体DNA甲基化与基因表达相关。然而，重复基因之间基因体DNA甲基化的偏差是否以及如何影响它们的分化在很大程度上仍未得到探索。在这里，我们旨在阐明基因体DNA甲基化在重复基因命运中的潜在作用。我们从拟南芥和水稻（粳稻亚种）基因组中鉴定出旁系同源基因对，并对它们的单碱基分辨率甲基化组数据进行了重新处理。我们发现，旁系同源基因中的甲基化与包括外显子数量/基因长度、表达水平和突变率在内的几个基因特性呈非线性相关。此外，我们证明了旁系同源基因中甲基化水平和模式的分化确实与它们的序列和表达分化呈正相关。即使在控制了其他已知影响旁系同源基因分化的混杂因素之后，这一结果仍然成立。我们观察到，甲基化水平分化可能比甲基化模式分化与旁系同源基因的表达分化更相关。最后，我们探索了可能导致旁系同源基因中基因体甲基化分化的机制。我们发现，外显子甲基化分化比内含子甲基化分化与表达分化的相关性更紧密。我们表明，由各种复制机制产生的旁系同源基因的基因组环境（例如，侧翼为转座元件和重复序列）与旁系同源基因的甲基化分化相关。总体而言，我们的结果表明，基因体DNA甲基化的变化可以为重复基因在植物基因组中发展出差异表达模式并经历不同的进化命运提供另一条途径。
