PT  - JOURNAL ARTICLE
AU  - Aleksandr B. Sahakyan
AU  - Shankar Balasubramanian
TI  - Core variability in mutation rates shapes the basal sequence characteristics of the human genome
AID  - 10.1101/024257
DP  - 2015 Jan 01
TA  - bioRxiv
PG  - 024257
4099  - http://biorxiv.org/content/early/2015/08/10/024257.2.short
4100  - http://biorxiv.org/content/early/2015/08/10/024257.2.full
AB  - Accurate knowledge on the core components of mutation rates is of vital importance to understand genome dynamics. By performing a single-genome and model-free analysis of 39894 retrotransposon remnants, we reveal core, sequence-dependent, nucleotide substitution rates (germline) at each of the 3.2 billion positions of 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 observed in the actual human genome, with or without repeat elements. This directly demonstrates the key role of the core nucleotide substitution rates in shaping the oligomeric composition of the human genome. We next generate the basal mutability profile of the human genome and show the depletion of the moieties with low basal mutability in the database of cancer mutations.