Mutation Rate Variation Across Genomic Regions in \textit{Arabidopsis thaliana}

TL;DR

This study investigates how chromatin features influence mutation rate variation across genes in Arabidopsis thaliana, revealing that active transcription marks are linked to lower mutation rates and reduced variability, with implications for evolutionary dynamics.

Contribution

It demonstrates that chromatin state predicts both the mean and variability of mutation rates across genes, a novel insight into mutation rate heterogeneity within a plant genome.

Findings

Histone marks associated with active transcription correlate with lower mutation rates.

Chromatin features significantly reduce mutation rate variability across genes.

GC content is positively associated with mutation-rate variability, independent of chromatin effects.

Abstract

In population genetics, mutation rate is often treated as a homogeneous parameter across the genome. Empirical evidence, however, shows systematic variation across genomic contexts associated with chromatin organization and epigenomic features. Using gene-level de novo mutation data from Arabidopsis thaliana, we test whether chromatin features predict not only the mean per-base mutation rate but also its variability across genes. To reduce heterogeneity in selective regime, we restrict analysis to essential and lethal loci subject to strong purifying selection. Across complementary multivariable models including heteroskedasticity-robust linear regression, length-weighted regression, and Poisson generalized linear models with exposure offsets, histone marks associated with active transcription (H3K4me1, H3K4me3, H3K36ac) are consistently associated with lower mean mutation rates and substantially reduced between-gene variance. GC content shows little association with the mean once chromatin predictors are controlled but is positively associated with mutation-rate variability. Estimates of skewness and kurtosis reveal no significant higher-order structure attributable to epigenomic predictors. A standardized Tajima's $D$ statistic yields directionally consistent but statistically underpowered associations with both the mean and variance of gene-level mutation rates. These results indicate that mutation rate is systematically structured by chromatin state within functionally constrained genes and suggest that evolutionary processes may act not only on expected mutation rate but also on its variability across loci.