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• W3023629690 abstract "We examined seventy million well-characterized human mutations, and their impact on G+C-compositional dynamics, in order to understand the formation and maintenance of major genomic nucleotide sequence patterns. Among novel mutations, those that change a strong (S) base pair G:C/C:G to a weak (W) pair A:T/T:A occur at nearly twice the frequency of the opposite mutations. Such imbalance puts strong downward pressure on overall GC-content. However, along protracted paths to fixation, S→W mutations are much less likely to propagate than W→S mutations. The magnitude of relative propagation disadvantages for S→W mutations is inexplicable by any currently-accepted model. This fact forced us to re-examine the quantitative features of Biased Gene Conversion (BGC) theory. Revised parameters of BGC that, per average individual, convert 7-14 W base pairs into S pairs, would account for the S-content turnover differences between new and old mutations, and make BGC an instrumental force for nucleotide dynamics and evolution. BGC should thus be considered seriously in both theories and biomedical practice. In particular, BGC should be taken into account during allele imputations, where missing SNP alleles are computationally predicted based on the information about several neighboring alleles. Finally, we analyzed the effect of neighboring nucleotide context on the mutation frequencies, dynamics, and GC-composition turnover. For this purpose, we examined genomic regions having extremely biased nucleotide compositions (enriched for S-, W-, purine/pyrimidine strand asymmetry, or AC/GT-strand asymmetry). It was found that point mutations in these regions preferentially degrade the nucleotide inhomogeneities, decreasing the sequence biases. Degradation of sequence bias is highest for novel mutations, and considerably lower for older mutations (those widespread across populations). Besides BGC, there may be additional, still uncharacterized molecular mechanisms that either preserve genomic regions with biased nucleotide compositions from mutational degradation or fail to degrade such inhomogeneities in specific chromosomal regions." @default.
• W3023629690 created "2020-05-13" @default.
• W3023629690 creator A5032577019 @default.
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• W3023629690 date "2020-04-30" @default.
• W3023629690 modified "2023-10-16" @default.
• W3023629690 title "Adapting Biased Gene Conversion theory to account for intensive GC-content deterioration in the human genome by novel mutations" @default.
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• W3023629690 doi "https://doi.org/10.1371/journal.pone.0232167" @default.
• W3023629690 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7192473" @default.
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