Virus Evolution

Suzuki, Yukiko; Wyndham, A.; Gojobori, T

doi:10.1002/0470022620.bbc12

Cited by 1 publication

(1 citation statement)

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“…The rates of nonsynonymous (dN) and synonymous (dS) mutations for each gene were computed by the ratio of number of nonsynonymous and synonymous changes to total number of nonsynonymous and synonymous sites respectively, using the mutation-fraction method 25 . To assess the statistical significance between any two sample sets, Z-test was applied to dS and dN values 26 .…”

Section: Methodsmentioning

confidence: 99%

Accelerated gene evolution through replication–transcription conflicts

Paul

Million-Weaver

Chattopadhyay

et al. 2013

Nature

131

184

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Summary Several mechanisms that increase the rate of mutagenesis across the entire genome have been identified; however, how the rate of evolution might be promoted in individual genes is unclear. A majority of the genes in bacteria are encoded on the leading strand of replication1–4. This presumably avoids the potentially detrimental head-on collisions that occur between the replication and transcription machineries when genes are encoded on the lagging strand1–4. We identified the ubiquitous (core) genes in Bacillus subtilis and determined that 17% of them are on the lagging strand. We found a higher rate of point mutations in the core genes on the lagging strand compared to those on the leading strand, with this difference being primarily in the amino acid changing (nonsynonymous) mutations. We determined that overall, the genes under strong negative selection against amino acid changing mutations tend to be on the leading strand, co-oriented with replication. In contrast, based on the rate of convergent mutations, genes under positive selection for amino acid changing mutations are more commonly found on the lagging strand, indicating faster adaptive evolution in many genes in the head-on orientation. Increased gene length and gene expression levels are positively correlated with the rate of accumulation of nonsynonymous mutations in the head-on genes, suggesting that the conflict between replication and transcription could be a driving force behind these mutations. Indeed, using reversion assays, we show that the difference in the rate of mutagenesis of genes in the two orientations is transcription-dependent. Altogether, our findings indicate that head-on replication-transcription conflicts are more mutagenic than co-directional conflicts and that these encounters can significantly increase adaptive structural variation in the coded proteins. We propose that bacteria, and potentially other organisms, promote faster evolution of specific genes through orientation-dependent encounters between DNA replication and transcription.

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Section: Methodsmentioning

confidence: 99%