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Modeling the effect of changing selective pressures on polymorphism and divergence.
MedLine Citation:
PMID:  23178187     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The most common models of sequence evolution used to make inferences about adaptation rely on the assumption that selective pressures at a site remain constant through time. Instead, one might plausibly imagine that a change in the environment renders an allele beneficial and that when it fixes, the site is now constrained-until another change in the environment occurs that affects the selective pressures at that site. With this view in mind, we introduce a simple dynamic model for the evolution of coding regions, in which non-synonymous sites alternate between being fixed for the favored allele and being neutral with respect to other alleles. We use the pruning algorithm to derive closed forms for observable patterns of polymorphism and divergence in terms of the model parameters. Using our model, estimates of the fraction of beneficial substitutions α would remain similar to those obtained from existing approaches. In this framework, however, it becomes natural to ask how often adaptive substitutions originate from previously constrained or previously neutral sites, i.e., about the source of adaptive substitutions. We show that counts of coding sites that are both polymorphic in a sample from one species and divergent between two others carry information about this parameter. We also extend the basic model to include the effects of weakly deleterious mutations and discuss the importance of assumptions about the distribution of deleterious mutations among constrained non-synonymous sites. Finally, we derive a likelihood function for the parameters and apply it to a toy example, variation data for coding regions from chromosome 2 of the Drosophila melanogaster subgroup. This modeling work underscores how restrictive assumptions about adaptation have been to date, and how further work in this area will help to reveal unexplored and yet basic characteristics of adaptation.
Authors:
Etam Benger; Guy Sella
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-21
Journal Detail:
Title:  Theoretical population biology     Volume:  -     ISSN:  1096-0325     ISO Abbreviation:  Theor Popul Biol     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0256422     Medline TA:  Theor Popul Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Institute of Mathematics and the Center for the Study of Rationality, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel.
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