Core variability in substitution rates and the basal sequence characteristics of the human genome
Sahakyan A., Balasubramanian S.
Abstract Accurate knowledge on the core components of substitution rates is of vital importance to understand genome evolution and dynamics. By performing a single-genome and direct analysis of 39894 retrotransposon remnants, we reveal germline sequence-dependent nucleotide substitution rates that can be assigned to each position in the human genome. Benefiting from the data made available in such detail, we show that a simulated genome, generated by equilibrating a random DNA sequence solely using our rate constants, exhibits nucleotide organisation close to that in the human genome. We next generate the germline basal substitution propensity (BSP) profile of the human genome and show a decreased tendency of moieties with low BSP to undergo somatic mutations in many cancer types.