Abstract
BackgroundThe f factor is a new parameter for accommodating the influence of both the starting and ending states in the rate matrices of "generalized weighted frequencies" (+gwF) models for sequence evolution. In this study, we derive an expected value for f, starting from a nearly neutral model of weak selection, and then assess the biological interpretation of this factor with evolutionary simulations.ResultsAn expected value of f = 0.5 (i.e., equal dependency on the starting and ending states) is derived for sequences that are evolving under the nearly neutral model of this study. However, this expectation is sensitive to violations of its underlying assumptions as illustrated with the evolutionary simulations.ConclusionThis study illustrates how selection, drift, and mutation at the population level can be linked to the rate matrices of models for sequence evolution to derive an expected value of f. However, as f is affected by a number of factors that limit its biological interpretation, this factor should normally be estimated as a free parameter rather than fixed a priori in a +gwF analysis.
Highlights
The f factor is a new parameter for accommodating the influence of both the starting and ending states in the rate matrices of "generalized weighted frequencies" (+gwF) models for sequence evolution
Felsenstein [1] was the first to introduce an evolutionary model for DNA sequences, which allows for unequal nucleotide frequencies
Derivation of the rate matrix for the weak selection model The nearly neutral model of molecular evolution states that most DNA mutations of longer-term evolutionary consequence are under weak selection and are prone to drift [7,8]
Summary
Derivation of the rate matrix for the weak selection model The nearly neutral model of molecular evolution states that most DNA mutations of longer-term evolutionary consequence are under weak selection and are prone to drift [7,8]. Violations of the weak selection model were incorporated in the simulations by: (1) heterogeneous sequences with sites drawn from different equilibrium base frequencies; (2) populations in disequilibrium due to changing Ne; and (3) an accelerated C to T substitution rate. Ne was either left unchanged or was suddenly changed by a certain factor The latter was done by replacing the rate matrix derived from equation (4), resulting in new equilibrium frequencies of the nucleotides. In the third set of simulations, an acceleration in the C to T substitution rate was incorporated, thereby modeling an increase in their mutation rate due to the deamination of methylated C's in CpG pairs [14] The introduction of this bias resulted in significant deviations of f in either direction from 0.5, even though their sequences were simulated in equilibrium (Fig. 2). The value of f can vary considerably when the rates for reciprocal mutations are unequal
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
