NDLI: Inference of Functional Divergence Among Proteins When the Evolutionary Process is Non-stationary

Content Provider	Springer Nature Link
Author	Bay, Rachael A. Bielawski, Joseph P.
Copyright Year	2013
Abstract	Functional shifts during protein evolution are expected to yield shifts in substitution rate, and statistical methods can test for this at both codon and amino acid levels. Although methods based on models of sequence evolution serve as powerful tools for studying evolutionary processes, violating underlying assumptions can lead to false biological conclusions. It is not unusual for functional shifts to be accompanied by changes in other aspects of the evolutionary process, such as codon or amino acid frequencies. However, models used to test for functional divergence assume these frequencies remain constant over time. We employed simulation to investigate the impact of non-stationary evolution on functional divergence inference. We investigated three likelihood ratio tests based on codon models and found varying degrees of sensitivity. Joint effects of shifts in frequencies and selection pressures can be large, leading to false signals for positive selection. Amino acid-based tests (FunDi and Bivar) were also compromised when several aspects of the substitution process were not adequately modeled. We applied the same tests to a core genome “scan” for functional divergence between light-adapted ecotypes of the cyanobacteria Prochlorococcus, and carried out gene-specific simulations for ten genes. Results of those simulations illustrated how the inference of functional divergence at the genomic level can be seriously impacted by model misspecification. Although computationally costly, simulations motivated by data in hand are warranted when several aspects of the substitution process are either misspecified or not included in the models upon which the statistical tests were built.
Starting Page	205
Ending Page	215
Page Count	11
File Format	PDF
ISSN	00222844
Journal	Journal of Molecular Evolution
Volume Number	76
Issue Number	4
e-ISSN	14321432
Language	English
Publisher	Springer-Verlag
Publisher Date	2013-02-27
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Power Accuracy Functional divergence Positive selection Non-stationary evolution Evolutionary Biology Microbiology Plant Sciences Plant Genetics & Genomics Animal Genetics and Genomics Cell Biology
Content Type	Text
Resource Type	Article
Subject	Genetics Molecular Biology Ecology, Evolution, Behavior and Systematics

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