Selection Threshold Severely Constrains Capture of Beneficial Mutations

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, ST d , which is the mid-point of the transition zone between selectable and un-selectable deleterious mutations. We showed that under most natural circumstances, ST d 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 (ST b) 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 ST b 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 lowimpact 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 ST b 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.

Can Purifying Natural Selection Preserve Biological Information?

“…For the sake of simplicity and clarity, this study does not address beneficial mutations, but we focus on this topic in a companion paper [28]. In that paper we show there is a selection threshold for beneficial mutations very similar in magnitude to the one for deleterious mutations.…”

“…This eliminates from consideration any absolutely neutral mutations. In this paper, for clarity and brevity, only detrimental mutations are considered, although the fate and impact of beneficial mutations are reported in a companion paper by Sanford et al [28].…”

Computational Evolution Experiments Reveal a Net Loss of Genetic Information Despite Selection

“…The aforementioned experiments with Avida have demonstrated genetic entropy, providing empirical evidence that selection thresholds exist, and showing that ineffective selection may pose a substantial barrier to the evolutionary origin and maintenance of complexity [24]. Experiments using Mendel have provided further evidence of a selection threshold, and have explored the evolutionary fate of both beneficial and deleterious mutations [5,[34][35][36].…”

“…Moreover, zero new functions evolve when fitness effects are ≤ 0.075, and those that have previously evolved break down. Likewise, experiments with Mendel have estimated a selection threshold of approximately 10 -4 to 10 -3 under conditions typical of mammalian populations [5,34]. The selection threshold can act as a barrier preventing the evolutionary origin and maintenance of novel adaptive genetic information.…”

“…This type of change is not sustainable and cannot constitute the sole source of progressive evolution. (For this reason, deleterious and beneficial mutations have heretofore been studied separately with Mendel, with high-impact beneficial mutations being studied as a special case [34].) Instead, plausible scenarios of progressive adaptive evolution must allow the deterministic elimination of most deleterious mutations through purifying selection.…”