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Probing evolutionary repeatability: neutral and double changes and the predictability of evolutionary adaptation.

Roy SW - PLoS ONE (2009)

Bottom Line: Out of 18 billion possible orders of single mutations leading from non-resistant to fully-resistant form, they found that only 27 (1.5x10(-7)%) pathways were characterized by consistently increasing resistance, thus only a tiny fraction of possible paths are accessible by positive selection.Allowing neutral changes (those that do not affect resistance) increases the number of accessible pathways considerably, from 27 to 629.Even when many of the assumptions of the analysis of Weinreich et al. (2006) are relaxed, I find that evolution to more highly cefotaxime resistant beta-lactamase proteins is still highly repeatable.

View Article: PubMed Central - PubMed

Affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America. royscott@ncbi.nlm.nih.gov

ABSTRACT

Background: The question of how organisms adapt is among the most fundamental in evolutionary biology. Two recent studies investigated the evolution of Escherichia coli in response to challenge with the antibiotic cefotaxime. Studying five mutations in the beta-lactamase gene that together confer significant antibiotic resistance, the authors showed a complex fitness landscape that greatly constrained the identity and order of intermediates leading from the initial wildtype genotype to the final resistant genotype. Out of 18 billion possible orders of single mutations leading from non-resistant to fully-resistant form, they found that only 27 (1.5x10(-7)%) pathways were characterized by consistently increasing resistance, thus only a tiny fraction of possible paths are accessible by positive selection. I further explore these data in several ways.

Principal findings: Allowing neutral changes (those that do not affect resistance) increases the number of accessible pathways considerably, from 27 to 629. Allowing multiple simultaneous mutations also greatly increases the number of accessible pathways. Allowing a single case of double mutation to occur along a pathway increases the number of pathways from 27 to 259, and allowing arbitrarily many pairs of simultaneous changes increases the number of possible pathways by more than 100 fold, to 4800. I introduce the metric 'repeatability,' the probability that two random trials will proceed via the exact same pathway. In general, I find that while the total number of accessible pathways is dramatically affected by allowing neutral or double mutations, the overall evolutionary repeatability is generally much less affected.

Conclusions: These results probe the conceivable pathways available to evolution. Even when many of the assumptions of the analysis of Weinreich et al. (2006) are relaxed, I find that evolution to more highly cefotaxime resistant beta-lactamase proteins is still highly repeatable.

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Related in: MedlinePlus

Probability of double changes and pathway repeatability.Path repeatability is shown as a function of the probability of double changes relative to single changes for forward mutations under both EVT (top trace) and truncating selection (bottom trace).
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pone-0004500-g003: Probability of double changes and pathway repeatability.Path repeatability is shown as a function of the probability of double changes relative to single changes for forward mutations under both EVT (top trace) and truncating selection (bottom trace).

Mentions: Again, the effect of these additional types of changes on repeatability depends on their relative probability. As with neutral mutations, if double mutations have a small probability relative to single mutations, repeatability is not drastically affected. Under either truncating or EVT selection, repeatability is reduced by around 15–25% when double mutations are 1% as likely as single mutations, and by around 60–75% when double mutations are 5% as likely. Interestingly, in contrast to the case with neutral mutations, repeatability does not strictly decrease with the relative probability of double mutations, but begins to increase when double changes are at similar probabilities to single changes (Figure 3). The explanation for this observation appears to be that as double mutations become likely, a few very short paths including one or two double changes reach high probabilities, contributing a large amount to repeatability.


Probing evolutionary repeatability: neutral and double changes and the predictability of evolutionary adaptation.

Roy SW - PLoS ONE (2009)

Probability of double changes and pathway repeatability.Path repeatability is shown as a function of the probability of double changes relative to single changes for forward mutations under both EVT (top trace) and truncating selection (bottom trace).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2643001&req=5

pone-0004500-g003: Probability of double changes and pathway repeatability.Path repeatability is shown as a function of the probability of double changes relative to single changes for forward mutations under both EVT (top trace) and truncating selection (bottom trace).
Mentions: Again, the effect of these additional types of changes on repeatability depends on their relative probability. As with neutral mutations, if double mutations have a small probability relative to single mutations, repeatability is not drastically affected. Under either truncating or EVT selection, repeatability is reduced by around 15–25% when double mutations are 1% as likely as single mutations, and by around 60–75% when double mutations are 5% as likely. Interestingly, in contrast to the case with neutral mutations, repeatability does not strictly decrease with the relative probability of double mutations, but begins to increase when double changes are at similar probabilities to single changes (Figure 3). The explanation for this observation appears to be that as double mutations become likely, a few very short paths including one or two double changes reach high probabilities, contributing a large amount to repeatability.

Bottom Line: Out of 18 billion possible orders of single mutations leading from non-resistant to fully-resistant form, they found that only 27 (1.5x10(-7)%) pathways were characterized by consistently increasing resistance, thus only a tiny fraction of possible paths are accessible by positive selection.Allowing neutral changes (those that do not affect resistance) increases the number of accessible pathways considerably, from 27 to 629.Even when many of the assumptions of the analysis of Weinreich et al. (2006) are relaxed, I find that evolution to more highly cefotaxime resistant beta-lactamase proteins is still highly repeatable.

View Article: PubMed Central - PubMed

Affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America. royscott@ncbi.nlm.nih.gov

ABSTRACT

Background: The question of how organisms adapt is among the most fundamental in evolutionary biology. Two recent studies investigated the evolution of Escherichia coli in response to challenge with the antibiotic cefotaxime. Studying five mutations in the beta-lactamase gene that together confer significant antibiotic resistance, the authors showed a complex fitness landscape that greatly constrained the identity and order of intermediates leading from the initial wildtype genotype to the final resistant genotype. Out of 18 billion possible orders of single mutations leading from non-resistant to fully-resistant form, they found that only 27 (1.5x10(-7)%) pathways were characterized by consistently increasing resistance, thus only a tiny fraction of possible paths are accessible by positive selection. I further explore these data in several ways.

Principal findings: Allowing neutral changes (those that do not affect resistance) increases the number of accessible pathways considerably, from 27 to 629. Allowing multiple simultaneous mutations also greatly increases the number of accessible pathways. Allowing a single case of double mutation to occur along a pathway increases the number of pathways from 27 to 259, and allowing arbitrarily many pairs of simultaneous changes increases the number of possible pathways by more than 100 fold, to 4800. I introduce the metric 'repeatability,' the probability that two random trials will proceed via the exact same pathway. In general, I find that while the total number of accessible pathways is dramatically affected by allowing neutral or double mutations, the overall evolutionary repeatability is generally much less affected.

Conclusions: These results probe the conceivable pathways available to evolution. Even when many of the assumptions of the analysis of Weinreich et al. (2006) are relaxed, I find that evolution to more highly cefotaxime resistant beta-lactamase proteins is still highly repeatable.

Show MeSH
Related in: MedlinePlus