Males Mutate More Than Females

Old fathers may be a genetic liability for their offspring. By analyzing a gene found on both the male and female sex chromosomes of birds, Swedish researchers have found evidence supporting the idea that older males are a source of the mutations that lead to genetic disease. The result, published in this month's Nature Genetics, also suggests that males have more input into evolutionary change than females.

For the last 90 years, geneticists have noted that children of older fathers tend to suffer from more genetic diseases. The standard explanation has been that fathers pass on more genetic mutations, because their sperm-producing cells divide throughout their lifetimes--as many as 400 times in a 30-year-old man. This provides many more chances for mistakes, as the DNA copies itself, than in egg cells, which only divide about 24 times.

The obvious way to test this idea in humans is to compare the mutation rate on the Y chromosome, which only males carry, with the female X chromosome. The trouble is that in the population overall, there is only one Y chromosome for every three Xs, and natural selection is less effective at weeding out harmful mutations from smaller numbers. Thus, a higher mutation rate on the Y might just reflect this quirk of chromosome numbers.

To avoid this confounding effect, evolutionary geneticist Hans Ellegren of the Swedish University of Agricultural Sciences in Uppsala and his graduate student Anna-Karin Fridolfsson turned to birds. In birds, the females have mismatched sex chromosomes, designated "W" and "Z," while males have two "Zs." Therefore, the chromosome arrangement should drive down the apparent mutation rate in the male chromosome--the Z. If the male mutation rate is still higher, it is likely to be a real effect. The team sequenced a gene called CHD from males and females of birds, including warblers, flycatchers, and yellowhammers. Applying a statistical method for analyzing mutation rates, they showed that the gene accumulated mutations in males as much as 6.5 times faster than in females.

Population geneticist Brian Charlesworth, of the University of Edinburgh, United Kingdom, cautions that more work will be needed to verify the Ellegren team's conclusion. Already, though, the new results should tell baby boomers and birds alike to beware: there may be unintended consequences of siring a family when you are a senior citizen.