Spontaneous mutation as a risk factor

Abstract

From various estimates of the mutation rate per nucleotide per generation, centering around 1-2 x 10(-8) and the number of nucleotide pairs, 3 x 10(9) per genome, the number of new mutations in a human zygote is very large, in the order of 100. The mutation rate is an order of magnitude higher in males than females, due presumably to the greater number of cell divisions in the male germ line, and increases more than linearly with paternal age. It is likely that a large fraction of these mutations are in unimportant 'junk' DNA, but if even 2% of the mutations are selected, this means two new deleterious mutations per generation. It is suggested that quasi-truncation selection is the most likely way in which this large number of mutations can be eliminated from the population without an excessive burden of reduced viability and fertility.