Using computer simulation to understand mutation accumulation dynamics and genetic load

Abstract

Long-standing theoretical concerns about mutation accumulation within the human population can now be addressed with numerical simulation. We apply a biologically realistic forward-time population genetics program to study human mutation accumulation under a wide-range of circumstances. Using realistic estimates for the relevant biological parameters, we investigate the rate of mutation accumulation, the distribution of the fitness effects of the accumulating mutations, and the overall effect on mean genotypic fitness. Our numerical simulations consistently show that deleterious mutations accumulate linearly across a large portion of the relevant parameter space. This appears to be primarily due to the predominance of nearly-neutral mutations. The problem of mutation accumulation becomes severe when mutation rates are high. Numerical simulations strongly support earlier theoretical and mathematical studies indicating that human mutation accumulation is a serious concern. Our simulations indicate that reduction of mutation rate is the most effective means for addressing this problem. © Springer-Verlag Berlin Heidelberg 2007.