BIOLOGICAL BASIS OF GERMLINE MUTATION - COMPARISONS OF SPONTANEOUS GERMLINE MUTATION-RATES AMONG DROSOPHILA, MOUSE, AND HUMAN

Spontaneous mutation rates per generation are similar among the three species considered here Drosophila, mouse, and human-and are not related to time, os is often assumed. Spontaneous germline mutation rates per generation averaged among loci are less variable among species than they ore among loci and tests and between gender. Mutation rates are highly variable over time in diverse lineages. Recent estimates of the number of germ cell divisions per generation ore: for humans, 401 (30-year generation) in males and 31 in females; for mice, 62 (9-month generation) in males and 25 in females; and for Drosophila melanogaster, 35.5 (18-day generation) in males and 36.5 (25-doy generation) in females. The relationships between germ cell division estimates of the two sexes in the three species closely reflect those between mutation rates in the sexes, although mutation rates per cell division vary among species. Whereas the overall rate per generation is constant among species, this consistency must be achieved by diverse mechanisms. Modifiers of mutation rates, on which selection might act, include germline characteristics that contribute disproportionately to the total mutation rates. The germline mutation rates between the sexes within a species ore largely influenced by germ cell divisions per generation. Also, a large portion of the total mutations occur during the interval between the beginning of meiosis and differentiation of the some from the germline. Significant genetic events contributing to mutations during this time may include meiosis, lack of DNA repair in sperm cells, methylation of CpG dinucleotides in mammalian sperm and early embryo, gonomeric fertilization, and rapid cleavage divisions. (C) 1995 Wiley Liss, Inc.