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Curr Genomics. 2012 Mar;13(1):55-64. doi: 10.2174/138920212799034730.

A blueprint for a mutationist theory of replicative strand asymmetries formation.

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Department of General Chemistry, Belarussian State Medical University, Belarus, Minsk, Dzerzinskogo, 83, Russia.


In the present review, we summarized current knowledge on replicative strand asymmetries in prokaryotic genomes. A cornerstone for the creation of a theory of their formation has been overviewed. According to our recent works, the probability of nonsense mutation caused by replication-associated mutational pressure is higher for genes from lagging strands than for genes from leading strands of both bacterial and archaeal genomes. Lower density of open reading frames in lagging strands can be explained by faster rates of nonsense mutations in genes situated on them. According to the asymmetries in nucleotide usage in fourfold and twofold degenerate sites, the direction of replication-associated mutational pressure for genes from lagging strands is usually the same as the direction of transcription-associated mutational pressure. It means that lagging strands should accumulate more 8-oxo-G, uracil and 5-formyl-uracil, respectively. In our opinion, consequences of cytosine deamination (C to T transitions) do not lead to the decrease of cytosine usage in genes from lagging strands because of the consequences of thymine oxidation (T to C transitions), while guanine oxidation (causing G to T transversions) makes the main contribution into the decrease of guanine usage in fourfold degenerate sites of genes from lagging strands. Nucleotide usage asymmetries and bias in density of coding regions can be found in archaeal genomes, although, the percent of "inversed" asymmetries is much higher for them than for bacterial genomes. "Homogenized" and "inversed" replicative strand asymmetries in archaeal genomes can be used as retrospective indexes for detection of OriC translocations and large inversions.


Chirochore; GC-content; isochore; mutational pressure; nonsense mutation; replichore.

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