Somatic mutations inferred from RNA-seq data highlight the contribution of replication timing to mutation rate variation in a model plant

Variation in the rates and characteristics of germline and somatic mutations across the genome of an organism is informative about DNA damage and repair processes and can also shed light on aspects of organism physiology and evolution. We adapted a recently developed method for inferring somatic mutations from bulk RNA-seq data and applied it to a large collection of Arabidopsis thaliana accessions. The wide range of genomic data types available for A. thaliana enabled us to investigate the relationships of multiple genomic features with the variation in the somatic mutation rate across the genome of this model plant. We observed that late replicated regions showed evidence of an elevated rate of somatic mutation compared to genomic regions that are replicated early. We identified transcriptional strand asymmetries, consistent with the effects of transcription-coupled damage and/or repair. We also observed a negative relationship between the inferred somatic mutation count and the H3K36me3 histone mark which is well documented in the literature of human systems. In addition, we were able to support previous reports of an inverse relationship between inferred somatic mutation count and guanine-cytosine content as well as a positive relationship between inferred somatic mutation count and DNA methylation for both cytosine and noncytosine mutations.