Abstract
Mutations are the ultimate source of genetic variation. To study mechanisms determining intragenomic mutation rate variability, we reanalyzed 43,483 de novo germline single base substitutions in 1,504 fast neutron irradiated mutation accumulation lines in Kitaake rice. Mutation rates were significantly lower in genomic regions marked by H3K4me1, a histone modification found in the gene bodies of actively expressed and evolutionarily conserved genes in plants. We observed conservation in rice for PDS5C, a cohesion cofactor involved in the homology-directed repair pathway that in A. thaliana binds to H3K4me1 via its Tudor domain and localizes to regions exhibiting reduced mutation rates: coding regions, essential genes, constitutively expressed genes, and genes under stronger purifying selection, mirroring mutation biases observed in rice as well. We find that Tudor domains are significantly enriched in DNA repair proteins (p<1e-11). These include the mismatch repair MSH6 protein, suggesting that plants have evolved multiple DNA repair pathways that target gene bodies and essential genes through H3K4me1 binding, which is supported by models of protein-peptide docking. These findings inspire further research to characterize mechanisms localizing DNA repair, potentially tuning the evolutionary trajectories of plant genomes.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
We add in silico models of protein-peptide interactions between Tudor domains of DNA repair proteins MSH6 and PDS5C and H3K4, H3K4me1, H3K4me2, H3K4me3 in A. thaliana and O. sativa.