A new study challenges the current belief of a high human male:female mutation ratio.

A recent comparison of a DNA region that was transposed from the X to the Y chromosome 3-4 million years ago, with the same region on the X chromosome showed only a slight excess of mutant changes on the Y chromosome. This translates to an estimate of 1.7 for the ratio of the male to female mutation rate, much less than the average 5.1 of previous studies. The authors argue that this throws doubt not only on higher male mutation rates in human ancestry, but also on the standard assumption of a high male:female ratio in contemporary human populations. Clearly, more studies are needed to clear up this discrepancy in the ancestral rates, but I believe that the high contemporary male:female ratio for base substitutions is too well established to be overthrown by even a very good evolutionary study.

The origins, patterns and implications of human spontaneous mutation.

The germline mutation rate in human males, especially older males, is generally much higher than in females, mainly because in males there are many more germ-cell divisions. However, there are some exceptions and many variations. Base substitutions, insertion-deletions, repeat expansions and chromosomal changes each follow different rules. Evidence from evolutionary sequence data indicates that the overall rate of deleterious mutation may be high enough to have a large effect on human well-being. But there are ways in which the impact of deleterious mutations can be mitigated.

Two centuries of genetics: a view from halftime.

In the first half-century of genetics, 1900 to 1953, the main techniques were breeding experiments and microscopy. Emphasis was on transmission genetics and cytogenetics, and during the half-century these became mature sciences. But the gene remained elusive. In 1953, thanks to Watson and Crick, the nature of the gene was no longer a mystery. In the second half of the century, the techniques became more chemical and computers played an indispensable role. The emphasis was then on gene action and, in the human, on increasingly accurate gene mapping and the soon-to-be-completed DNA sequence. During the first half-century, human genetics was very primitive, but by the end of the century it was comparable to that of the best-studied species. This trend will surely extend to the next century. The humanitarian possibilities of new techniques are enormous, but social judgments about their use and the problems of an increasingly crowded planet temper our optimism.

Rates of spontaneous mutation.

Rates of spontaneous mutation per genome as measured in the laboratory are remarkably similar within broad groups of organisms but differ strikingly among groups. Mutation rates in RNA viruses, whose genomes contain ca. 10(4) bases, are roughly 1 per genome per replication for lytic viruses and roughly 0.1 per genome per replication for retroviruses and a retrotransposon. Mutation rates in microbes with DNA-based chromosomes are close to 1/300 per genome per replication; in this group, therefore, rates per base pair vary inversely and hugely as genome sizes vary from 6 x 10(3) to 4 x 10(7) bases or base pairs. Mutation rates in higher eukaryotes are roughly 0.1-100 per genome per sexual generation but are currently indistinguishable from 1/300 per cell division per effective genome (which excludes the fraction of the genome in which most mutations are neutral). It is now possible to specify some of the evolutionary forces that shape these diverse mutation rates.