Can Purifying Natural Selection Preserve Biological Information?

Abstract

Most deleterious mutations have very slight effects on total fitness, and it has become clear that below a certain fitness effect threshold, such low-impact mutations fail to respond to natural selection. The existence of such a selection threshold suggests that many low-impact deleterious mutations should accumulate continuously, resulting in relentless erosion of genetic information. In this paper, we use numerical simulation to examine this problem of selection threshold. The objective of this research was to investigate the effect of various biological factors individually and jointly on mutation accumulation in a model human population. For this purpose, we used a recently-developed, biologically-realistic numerical simulation program, Mendel’s Accountant. This program introduces new mutations into the population every generation and tracks each mutation through the processes of recombination, gamete formation, mating, and transmission to the new offspring. This method tracks which individuals survive to reproduce after selection, and records the transmission of each surviving mutation every generation. This allows a detailed mechanistic accounting of each mutation that enters and leaves the population over the course of many generations. We term this type of analysis genetic accounting. Across all reasonable parameters settings, we observed that high impact mutations were selected away with very high efficiency, while very low impact mutations accumulated just as if there was no selection operating. There was always a large transitional zone, wherein mutations with intermediate fitness effects accumulated continuously, but at a lower rate than would occur in the absence of selection. To characterize the accumulation of mutations of different fitness effect we developed a new statistic, selection threshold (ST d ), which is an empirically determined value for a given population. A population’s selection threshold is defined as that fitness effect wherein deleterious mutations are accumulating at exactly half the rate expected in the absence of selection. This threshold is mid-way between entirely selectable, and entirely unselectable, mutation effects. Our investigations reveal that under a very wide range of parameter values, selection thresholds for deleterious mutations are surprisingly high. Our analyses of the selection threshold problem indicate that given even modest levels of noise affecting either the genotype-phenotype relationship or the genotypic fitness-survival-reproduction relationship, accumulation of low-impact mutations continually degrades fitness, and this degradation is far more serious than has been previously acknowledged. Simulations based on recently published values for mutation rate and effect-distribution in