Human population genetics in the 1960s was obsessed with the question of genetic load. Much of the motivation was concern about health consequences of radiation and nuclear weapons. We now know that radiation does bad things to organisms but that the mutation rate in mammals is nearly insensitive to the effects of ionizing radiation. No one knew that then. Popular concern about the issue was also pumped up by monster movies, which were everywhere on late night television. Does anyone remember Godzilla?
A related and more basic problem at the time was the maintenance of diversity in populations. As more and more technologies for examining diversity came along, from blood groups to electrophoretic variants of proteins to restriction fragment polymorphisms and so on, more and more variation in our DNA popped out, to everyone’s surprise. What kept it around? An insightful and readable introduction the time was written by James Crow in 20081. (You will look long and hard, by the way, for a Crow paper that is not both insightful and readable.) This fundamental problem has also been forgotten, buried under the wave of neutralism.
The key paper about load was published in 19582. Morton, Crow, and Muller showed that, under some simplifying assumptions, the regression of mortality (and on other traits like IQ) on the inbreeding coefficient could reveal the nature of our burden of mutations. In particular the negative logarithm of the rate, for example the infant mortality rate, should be linear in the inbreeding coefficient:
-ln(q) = A + Bf
where q is the mortality rate and f the inbreeding coefficient. Their important insight was the if our load is mostly deleterious recessives then the rate should increase rapidly with inbreeding. If, on the other hand, our load reflects a lot of balanced polymorphisms then the load should not increase very much with inbreeding. In particular the load ratio, B/A, ought to be something like 10 if there are a lot of deleterious recessives while something like 2 if there are a lot of balanced polymorphisms. A clear explanation of the the theory and the results availabe by the early 1970s can be found in the classic Cavalli and Bodmer text3.
The bottom line was that load ratios from human populations did not give a clear signal either way. A typical B/A ratio was something like 4. The interest in and optimism about load theory in 1960 had fizzled by 1970.
Today all those issues are back on the table in a big way. What is our burden of mutation? How many of our aches and pains and premature deaths are costs of balanced polymorphism? Unfortunately the whole toolkit of 50 years ago has been mostly forgotten by the current generation of human population geneticists. A shame.
1. Crow, J.F., 2008. Mid-century controversies in population genetics. Annual review of genetics 42, 1-16.
2. Morton, N.E., Crow, J.F., Muller, H.J., 1956. An estimate of the mutational damage in man from data on consanguineous marriages. Proc. Nat. Acad. Sci USA 42, 855-863.
3. Cavalli-Sforza, L.L., Bodmer, W.F., 1971. The Genetics of Human Populations. W. H. Freeman.