Fig 1.
Nucleosomes and human genetic variation, and mutations.
A, Nucleosome occupancy scores (NOS) around flagged SNPs and common SNPs. B, The average transition to transversion ratio in 1,000 bp bins as a function of NOS, calculated from 1,092 individuals. C, The ancestral transition to transversion ratio calculated for 10 groups corresponding to increasing nucleosome occupancy. D, Normalized base-specific mutation rates (MR) of 10 groups corresponding to increasing nucleosome occupancy. E, Ancestral AA→AG MR in relation to nearest dyad. F, Fast Fourier transform (FFT) of the AA→AG MR. G, Effect of increasing nucleosome occupancy on germline mutations, asterisk denotes statistical significance (p-value < 0.01 by Z-test with Bonferroni correction) between first and last group.
Fig 2.
Nucleosome occupancy and cancer mutations.
A, Cancer non-coding mutation rate (MR) in relation to nucleosome occupancy scores (NOS) with a Pearson’s correlation coefficient (PCC) of 0.833. Bottom x-axis corresponds to the bar graph depicting the NOS for 10 equally sized groups of increasing nucleosome occupancy. Top x-axis corresponds to the scatter plot depiction of the same data for each individual NOS. B, Raw counts of Cancer SNVs in relation to dyads. C, Cancer indel and microindel counts in relation to absolute distance to nearest dyad. Two small enrichments of indels are at 74 and 115 bp which correspond to the theoretical start and end locations of linker DNA between two nucleosomes. D, The total cancer (coding and non-coding) mutation rate as a function of NOS, Pearson’s correlation coefficient (PCC) of 0.989. Bottom x-axis corresponds to the bar graph depicting the NOS for 10 equally sized groups of increasing nucleosome occupancy. Top x-axis corresponds to the scatter plot depiction of the same data for each individual NOS.
Fig 3.
Effect of nucleosome occupancy on mutation rate in DNA repair deficient yeast.
The non-coding mutation rate in yeast that lack DNA repair machinery in relation to nucleosome occupancy scores (NOS) with a Pearson’s correlation coefficient (PCC) of 0.048. Bottom x-axis corresponds to the bar graph depicting the NOS for 10 equally sized groups of increasing nucleosome occupancy. Top x-axis corresponds to the scatter plot depiction of the same data for each individual NOS.