Upper limit of the rate and per generation effects of deleterious genomic mutations

Abstract

Unbiased or upper limit estimates of the rate (U) of genomic mutations to mildly deleterious alleles are crucial in genetic and conservation studies and in human health care. However, only a few estimates of the lower bounds of U are available. We present a fairly robust estimation that yields an upper limit of U and a nearly unbiased estimate of the per generation fitness decline due to new deleterious mutations. We applied the approach to three species of the freshwater microcrustacean Daphnia and revealed that the upper limit of U for egg survivorship is 0.73 (SD = 0.30) in 14 D. pulicaria populations. For the first four clutches, per generation decline in fecundity due to deleterious mutations ranged from 2.2% to 7.8% in 20 D. pulex populations and from 1.1% to 5.1% in 8 D. obtusa populations. These results indicate the mutation pressure is high in natural Daphnia populations. The approach investigated here provides a potential way to quickly and conveniently characterize U and per generation effects of deleterious genomic mutations on fitness or its important components such as fecundity.

Hitchhiking of Deleterious Alleles and the Cost of Adaptation in Partially Selfing Species

“…In general, mutations are deleterious, so these adaptive alleles are likely to arise in close linkage with deleterious sites. Estimates of the deleterious mutation rate range from 0.07 to 0.1 mutations per generation per genome in Arabidopsis (Ossowski et al 2010;Rutter et al 2012), 0.4 in Caenorhabditis elegans (Denver et al 2004), and upper limits of 0.6-0.8 in Daphnia pulex (Lynch et al 1998;Deng et al 2006). Further empirical estimates of the distribution of fitness effects in facultative sexuals, and partially selfing organisms, will be important to determine the effect of advantageous-deleterious interactions on the evolution of mating systems.…”

Measurements of spontaneous rates of mutations in the recent past and the near future

“…In particular, nucleotide diversity at the sequence level is 4N e m in diploids, and thus can be used to estimate m (Deng & Lynch 1996;Kondrashov 1998;Li & Deng 2005;Deng et al 2006;Messer 2009). However, because N e is not known independently, this relationship is more useful for estimating N e and not m (Kondrashov 1998;Caballero 2006).…”

Estimation of the upper limit of the mutation rate and mean heterozygous effect of deleterious mutations

“…Analogous estimators can be obtained for the case of naturally segregating inbred populations (Deng et al, 2006). For example, the estimated upper limit of U was generally no more than twice the true value under the different simulation cases (see table 1 of Deng et al, 2006). They concluded that the estimation of U and Uhs is not greatly biased.…”

“…Analogous estimators can be obtained for the case of naturally segregating inbred populations (Deng et al, 2006). Analogous estimators can be obtained for the case of naturally segregating inbred populations (Deng et al, 2006).…”

“…By means of computer simulations, Deng et al (2006) tried to quantify the amount of bias in the estimated upper limit of U when W max <1, both under MSB and for a model of balancing selection where overdominant mutations for the fitness trait under study are considered in addition to the dominant mutations. Here I point out that some of the models and parameters used by Deng et al (2006) are such that a possible overestimation of U and Uhs is minimized, and that other models and parameters may change the conclusions dramatically. For example, the estimated upper limit of U was generally no more than twice the true value under the different simulation cases (see table 1 of Deng et al, 2006).…”