Detecting Signatures of Positive Selection against a Backdrop of Compensatory Processes.
There are known limitations in methods of detecting positive selection. Common methods do not enable differentiation between positive selection and compensatory covariation, a major limitation. Further, the traditional method of calculating the ratio of nonsynonymous to synonymous substitutions (dN/dS) does not take into account the 3D structure of biomacromolecules nor differences between amino acids. It also does not account for saturation of synonymous mutations (dS) over long evolutionary time that renders codon-based methods ineffective for older divergences. This work aims to address these shortcomings for detecting positive selection through the development of a statistical model that examines clusters of substitutions in clusters of variable radii. Additionally, it uses a parametric bootstrapping approach to differentiate positive selection from compensatory processes. A previously reported case of positive selection in the leptin protein of primates was reexamined using this methodology.
['Chi|Peter B|PB|', 'Kosater|Westin M|WM|', 'Liberles|David A|DA|']
D000818:Animals D019143:Evolution, Molecular D020738:Leptin D015233:Models, Statistical D011323:Primates D011487:Protein Conformation D012641:Selection, Genetic D000069456:Silent Mutation D012984:Software
compensatory covariation positive directional selection protein structure evolution