Evolutionary pressures on proteins are often quantified by the ratio of substitution rates at non-synonymous and synonymous sites. The dN/dS ratio was originally developed for application to distantly diverged sequences, the differences among which represent substitutions that have fixed along independent lineages. Nevertheless, the dN/dS measure is often applied to sequences sampled from a single population, the differences among which represent segregating polymorphisms. Here, we study the expected dN/dS ratio for samples drawn from a single population under selection, and we find that in this context, dN/dS is relatively insensitive to the selection coefficient. Moreover, the hallmark signature of positive selection over divergent lineages, dN/dS>1, is violated within a population. For population samples, the relationship between selection and dN/dS does not follow a monotonic function, and so it may be impossible to infer selection pressures from dN/dS. These results have significant implications for the interpretation of dN/dS measurements among population-genetic samples.
%0 Journal Article
%1 kryazhimskiy2008population
%A Kryazhimskiy, Sergey
%A Plotkin, Joshua B
%C United States
%D 2008
%J PLoS genetics
%K coding_changes dNdS molecular_evolution
%N 12
%P e1000304--e1000304
%R 10.1371/journal.pgen.1000304
%T The population genetics of dN/dS
%U https://pubmed.ncbi.nlm.nih.gov/19081788
%V 4
%X Evolutionary pressures on proteins are often quantified by the ratio of substitution rates at non-synonymous and synonymous sites. The dN/dS ratio was originally developed for application to distantly diverged sequences, the differences among which represent substitutions that have fixed along independent lineages. Nevertheless, the dN/dS measure is often applied to sequences sampled from a single population, the differences among which represent segregating polymorphisms. Here, we study the expected dN/dS ratio for samples drawn from a single population under selection, and we find that in this context, dN/dS is relatively insensitive to the selection coefficient. Moreover, the hallmark signature of positive selection over divergent lineages, dN/dS>1, is violated within a population. For population samples, the relationship between selection and dN/dS does not follow a monotonic function, and so it may be impossible to infer selection pressures from dN/dS. These results have significant implications for the interpretation of dN/dS measurements among population-genetic samples.
@article{kryazhimskiy2008population,
abstract = {Evolutionary pressures on proteins are often quantified by the ratio of substitution rates at non-synonymous and synonymous sites. The dN/dS ratio was originally developed for application to distantly diverged sequences, the differences among which represent substitutions that have fixed along independent lineages. Nevertheless, the dN/dS measure is often applied to sequences sampled from a single population, the differences among which represent segregating polymorphisms. Here, we study the expected dN/dS ratio for samples drawn from a single population under selection, and we find that in this context, dN/dS is relatively insensitive to the selection coefficient. Moreover, the hallmark signature of positive selection over divergent lineages, dN/dS>1, is violated within a population. For population samples, the relationship between selection and dN/dS does not follow a monotonic function, and so it may be impossible to infer selection pressures from dN/dS. These results have significant implications for the interpretation of dN/dS measurements among population-genetic samples.},
added-at = {2024-04-23T17:52:55.000+0200},
address = {United States},
author = {Kryazhimskiy, Sergey and Plotkin, Joshua B},
biburl = {https://www.bibsonomy.org/bibtex/286c4ea375c5d07783ad4f68985fd94bb/peter.ralph},
comment = {19081788[pmid]
PMC2596312[pmcid]},
doi = {10.1371/journal.pgen.1000304},
interhash = {6cfab1c9524082ffd42ec0fcddb7d51e},
intrahash = {86c4ea375c5d07783ad4f68985fd94bb},
issn = {15537390},
journal = {PLoS genetics},
keywords = {coding_changes dNdS molecular_evolution},
month = dec,
number = 12,
pages = {e1000304--e1000304},
timestamp = {2024-04-23T17:52:55.000+0200},
title = {The population genetics of {dN/dS}},
url = {https://pubmed.ncbi.nlm.nih.gov/19081788},
volume = 4,
year = 2008
}