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Selection Threshold Severely Constrains Capture of Beneficial Mutations

    https://doi.org/10.1142/9789814508728_0011Cited by:4 (Source: Crossref)
    Abstract:

    Background. In a companion paper, careful numerical simulation was used to demonstrate that there is a quantifiable selection threshold, below which low-impact deleterious mutations escape purifying selection and, therefore, accumulate without limit. In that study we developed the statistic, STd, which is the mid-point of the transition zone between selectable and un-selectable deleterious mutations. We showed that under most natural circumstances, STd values are surprisingly high, such that the large majority of all deleterious mutations are un-selectable. Does a similar selection threshold exist for beneficial mutations?

    Methods. As in our companion paper we here employ what we describe as genetic accounting to quantify the selection threshold (STb) for beneficial mutations, and we study how various biological factors combine to determine its value.

    Results. In all experiments that employ biologically reasonable parameters, we observe high STb values and a general failure of selection to preferentially amplify the large majority of beneficial mutations. High-impact beneficial mutations strongly interfere with selection for or against all low-impact mutations.

    Conclusions. A selection threshold exists for beneficial mutations similar in magnitude to the selection threshold for deleterious ones, but the dynamics of that threshold are different. Our results suggest that for higher eukaryotes, minimal values for STb are in the range of 10−4 to 10−3. It appears very likely that most functional nucleotides in a large genome have fractional contributions to fitness much smaller than this. This means that, given our current understanding of how natural selection operates, we cannot explain the origin of the typical functional nucleotide.