What would happen if people moved somewhere where the mutation rate was far lower?
Their genetic load would decrease with time, assuming that they were still subject to much selection. Today, everybody has hundreds of nicked or broken genes: selection keeps eliminating them, while mutation keeps creating them. The suspicion is that their effect is quite large. This hypothetical population would have fewer and fewer. In a few thousand years, they would lose most of the variants that decrease fitness by 1% or more.
Posted on July 14, 2012 by gcochran9
Several recent papers give me the impression that there is regional variation in mutational load. One can slice this a number of ways. Dan MacArthur and company looked for mutations that knocked out genes – loss-of-function or LOF mutations. Mutational load is the sum of all deleterious mutations – LOF mutations are a clear-cut subset of total mutational load.
Some of the LOF mutations they are found are common, and are presumably neutral, maybe even beneficial, but most are rare and likely deleterious. The kicker is that they found significantly more LOF mutations in their African population sample than in their European and East Asian samples – 25% higher. That was unexpected.
Population history (and mutation rate) determine the variation you expect to find in neutral genes, but significantly deleterious mutations should be in mutation-selection balance. A neutral variant might easily be a million years old, but a deleterious variant will last, on average, 1/s generations, when s is the decrease in fitness caused by that variant. A mutation that decreases fitness by 1% should disappear in 100 generations or so, about 2500 years. Ancient bottlenecks should not influence the frequency of such noticeably deleterious mutations.
Another related paper, by Jacob Tenessen et al, looked at a large set of coding genes, sequencing many times (average depth of 111x) for high accuracy. As in in MacArthur’s paper they found that the average person carries many probably-deleterious mutations, mutations which are individually rare. Each person carried, on average, mutations expected to change function (almost always for the worse, although usually only a little for the worse) in 313 genes (out of the 15,585 they studied.
They looked at African-Americans and Americans of European descent, about a thousand of each. They saw what MacArthur’s group did: there were significantly more probably-deleterious mutations in the 80%-African population. When they used a loose definition of functional variation, about 20% more : with a more conservative definition, which should have a higher fraction of truly deleterious genes, about 29% more.
... The only simple explanation (that I can think of) is a higher mutation rate.
Posted on July 16, 2012 by harpend=
The model that Greg is dancing around suggests (1) that there is variation in mutation rate dependent on temperature or something correlated with temperature, (2) higher mutation rates cause a higher genetic burden in human populations, (3) leading to IQ reduction and other minor dings
While not fully or explicitly articulated, this is the first New Big Theory of race differences in quite a while, and an interesting alternative to the reigning sociobiological models available since the 1980s. In the latter models intelligence and reproductive differences are seen as consequences of natural selection in divergent latitudes, but this new model replaces natural selection with accumulated mutational burdens. The differences at lower latitudes are not selectively advantageous, but dysfunctional.
Dr. Cochran notes that complex adaptive systems, involving the functioning of many genes, should be the most vulnerable to genetic load, so this would obviously be the brain and probably reproductive physiology. So in addition to higher general mortality, dysfunctions associated with mutational burdens might include:
- Lower intelligence
- Higher retardation
- Higher mental illness
- Lower birthweight
- Higher premature births
- Higher infertility
- Higher reproductive deformities
- Higher miscarriage (and general obstetric complications)
- Lower sperm quality
Of course there is a difference between establishing population differences in genetic load, and proving that this is related to population differences in socially valued traits. I’m not sold on this as a replacement for sociobiological models, although there are aspects that make it useful and attractive in different ways. For example, I recently found that ethnic differences in rate of homosexuality are inversely correlated with latitude. Since theories of selectively advantageous homosexuality fall flat, this theory seemed like a better fit.