Homologous recombination and the pattern of nucleotide substitution in Ehrlichia ruminantium

Hughes, Austin L.; French, Jeffrey O.

doi:10.1016/j.gene.2006.08.003

Cited by 29 publications

(27 citation statements)

References 34 publications

(41 reference statements)

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“…In preliminary analyses, complicated methods making more assumptions (Li 1993;Yang and Nielsen 2000) yielded essentially identical results, as has been found in other studies when the number of substitutions per site is small, as in the present data (Hughes and French 2007). Within each of the 222 sequence datasets, we computed the synonymous nucleotide diversity (π S ), which is the mean of d S values for all pairwise comparisons; and the nonsynonymous nucleotide diversity (π N ), which is the mean of d N values for all pairwise comparisons (Nei and Kumar 2000).…”

Section: Methodssupporting

confidence: 90%

More effective purifying selection on RNA viruses than in DNA viruses

Hughes

2007

Gene

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Analysis of the pattern of nucleotide diversity in 222 independent viral sequence datasets showed the prevalence of purifying selection. In spite of the higher mutation rate of RNA viruses, our analyses revealed stronger evidence of the action of purifying selection in RNA viruses than in DNA viruses. The ratio of nonsynonymous to synonymous nucleotide diversity was significantly lower in RNA viruses than in DNA viruses, indicating that nonsynonymous mutations have been removed at a greater rate (relative to the mutation rate) in the former than in the latter. Moreover, statistics that measure the occurrence of rare polymorphisms revealed significantly a greater excess of rare nonsynonymous polymorphisms in RNA viruses than in DNA viruses but no difference with respect to synonymous polymorphisms. Since rare nonsynonymous polymorphisms are likely to be undergoing the effects of purifying selection acting to eliminate them, this result implies a stronger signature of ongoing purifying selection in RNA viruses than in DNA viruses. Across datasets from both DNA viruses and RNA viruses, we found a negatively allometric relationship between nonsynonymous and synonymous nucleotide diversity; in other words, nonsynonymous nucleotide diversity increased with synonymous nucleotide diversity at a less than linear rate. These findings are most easily explained by the occurrence of slightly deleterious mutations. The fact that the negative allometry was more pronounced in RNA viruses than in DNA viruses provided additional evidence that purifying selection is more effective in the former than in the latter.

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Section: Methodssupporting

confidence: 90%

More effective purifying selection on RNA viruses than in DNA viruses

Hughes

2007

Gene

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“…Standard errors of π S , π N , and π were estimated by the bootstrap method, which takes into account the non-independence of pairwise comparisons (Nei and Kumar 2000); and z-tests were used to test equality of nucleotide diversities in different genomic regions. In preliminary analyses, more complicated methods for estimating d, d S , and d N yielded essentially identical results, as has been found in other studies when the number of substitutions per site is small (Hughes and French 2007), as in the present data.…”

Section: Nucleotide Sequence Diversitysupporting

confidence: 90%

Nucleotide sequence polymorphism in circoviruses

Hughes

Piontkivska

2008

Infection, Genetics and Evolution

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Analysis of nucleotide diversity within six species of circovirus showed consistently stronger purifying selection at nonsynonymous sites in the rep gene than on those in the cap gene. In addition, synonymous nucleotide diversity in the rep gene was significantly lower than that in the cap gene, suggesting functional constraint even at synonymous sites in rep, which was associated in all six species with strongly negative AT-skew. Of the six virus species examined, four species showed evidence of ongoing purifying selection at nonsynonymous polymorphic sites in the rep gene, indicating the presence of slightly deterious nonsynonymous variants in these populations. The rep gene of porcine circovirus 2 (PCV2) was unique, however, in showing a strong excess of rare nonsynonymous polymorphisms. The excess of rare nonsynonymous polymorphisms suggests a prolonged population bottleneck in PCV2, allowing slightly deleterious mutations to accumulate, followed by a population expansion during which selection to remove these variants has increased in effectiveness. Such a population history is consistent with the epidemiological evidence of a recent worldwide spread of PCV2.

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“…This pattern is predicted because the neutral theory predicts that most nonsynonymous mutations are harmful to protein function and thus will tend to be eliminated by purifying selection, whereas synonymous mutations are much more likely to be selectively neutral or nearly so. The fact that the vast majority of genes show this pattern provides strong support for the neutral theory (Li et al, 1985;Endo et al, 1996;Hughes and Friedman, 2005;Hughes and French, 2007).…”

Section: Historical Background Neo-darwinismmentioning

confidence: 83%

“…In some cases, reporting evidence of positive selection, especially when the evidence is based on conservative tests, may serve to stimulate further studies that will examine the function of the gene involved and suggest possible mechanisms for the apparent positive selection (Hughes and French, 2007). On the other hand, it may prove difficult to test certain claims of positive selection that have been proposed on the basis of statistical arguments alone.…”

Section: Conclusion: Does It Matter?mentioning

confidence: 99%

Looking for Darwin in all the wrong places: the misguided quest for positive selection at the nucleotide sequence level

2007

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Recent years have seen an explosion of interest in evidence for positive Darwinian selection at the molecular level. This quest has been hampered by the use of statistical methods that fail adequately to rule out alternative hypotheses, particularly the relaxation of purifying selection and the effects of population bottlenecks, during which the effectiveness of purifying selection is reduced. A further problem has been the assumption that positive selection will generally involve repeated amino-acid changes to a single protein. This model was derived from the case of the vertebrate major histocompatibility complex (MHC), but the MHC proteins are unusual in being involved in proteinprotein recognition and in a co-evolutionary process of pathogens. There is no reason to suppose that repeated amino-acid changes to a single protein are involved in selectively advantageous phenotypes in general. Rather adaptive phenotypes are much more likely to result from other causes, including single amino-acid changes; deletion or silencing of genes or changes in the pattern of gene expression.

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Homologous recombination and the pattern of nucleotide substitution in Ehrlichia ruminantium

Cited by 29 publications

References 34 publications

More effective purifying selection on RNA viruses than in DNA viruses

More effective purifying selection on RNA viruses than in DNA viruses

Nucleotide sequence polymorphism in circoviruses

Looking for Darwin in all the wrong places: the misguided quest for positive selection at the nucleotide sequence level

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