At this point, it seems that paternal age is a significant driver of the human mutation rate, likely the main driver. Obviously this implies that many medical problems are more common in the children of older fathers, which is known to be the case. Less obviously, it implies that a population that has had high average paternal age for a long time will have a higher-than-average mutational load. This may well explain preliminary results that seem to show such differences.

Observed differences in paternal age are large enough to generate the sort of differences that have been observed so far. For example, judging from the Decode study, the mutation rate in a population with an average paternal age of 34 would be > 20% higher than that in a population with an average paternal age of 28.

If paternal age had increased significantly in the last generation, the genetic impact would be simple. The kinds of medical problems that are associated with high paternal age would increase. Although even that isn’t quite as simple as you might think, because, in practice, only problems that exceed a certain threshold of practical importance are officially noticed. If a kid has schizophrenia, or a cleft palate, a medical problem is deemed to exist. But suppose there was a mutation that dropped someone’s IQ by 1 pt: that would never be noticed at the individual level. There is every reason to think that advanced paternal age also increases the rate of such small-effect mutations – and over many generations such effects can add up. So, if a population had adopted late fatherhood 500 years ago, increasing the overall mutation rate by 50%, you would expect to see an elevated level of large effect mutations, but also an elevated level of mutations with effects on the order of 5% or greater. The class of 1% mutation would only gone up ~10%. If the pattern had been around for 5000 years, the class of 1% mutations would have increased by about 43%.

Moreover, although only a smallish fraction of kids suffer bad effects from having had an elderly father in a population in which this is generally rare, a long-term pattern of advanced paternal age must eventually result in the entire population having an unusually high level of medium- and small-effect deleterious alleles. That burden would be roughly Poissonian, and would vary between individuals, but there might not be much overlap in burden between populations.

A disease syndrome caused by one large-effect mutation has a fair chance of being pleiotropic. That is to say, it pushes the whole phenotype in a funny direction. The victim might be funny-looking, as well as retarded. An unusually large number of small-effect deleterious mutations shouldn’t push the phenotype in any particular direction, other than reduced performance.

The poster-boy population for checking out the consequences of a long-term pattern of advanced paternal age has to be the Australian Aborigines. They are not the only population of interest – there are other cultural patterns that change average paternal age. Like polygamy.

Someone should have noticed this a long time ago. Weinberg noticed increasing levels of trouble with parental age 100 years ago. Haldane had figured out that most mutations were contributed by males in 1947. He also developed the theory of genetic load before 1960. The atypical paternal age of Australian Aborigines has been well-documented for a long time.

Haldane should have noticed, and for all I know he did, but I’m not aware that he published anything about it. Thinking about it, I’d bet the bastard knew. Anyhow, he died in 1964. My guess is that relatively few people were simultaneously familiar with the evidence for male-biased mutation, paternal-age evidence in medicine, the theory of genetic load, and ethnographic reports of big differences in average paternal age. Genetic load went out of fashion, as did population genetics generally, and of courser no sensible person pays any attention to anthropologists.

I said a few months ago that there was still plenty of low-hanging fruit in biomedicine. There still is.