6 - Using the coalescent to interpret gene trees

Summary

Human genetic diversity: is it old?

In the last decade, molecular biology has provided sophisticated technology for assaying DNA polymorphisms, and considerable research effort has been devoted to characterizing human variability at the DNA level. Many geneticists are concentrating on the DNA variation that explains human diversity at the phenotypic level, with particular attention being given to genetic diseases. Most of the disease alleles so far identified have restricted geographic distributions, are relatively rare, and were probably generated by recent mutation events. Cystic fibrosis is an example of a genetic disease prevalent in Europe and estimated to have arisen perhaps 53000 years ago (Morral et al., 1993). A few disease alleles with similarly restricted geographical distributions, are much more common, clearly as the result of powerful selection. Such are the haemoglobinopathies which are subject to malarial selection. Allelic variants occur at both the α- and β-globin genes, causing α- and β-thalassaemias, sickle-cell anaemia and other traits and diseases. It is difficult to judge whether they arose very recently, possibly even within the last 10000 years, or are older, say 50 000–100 000 years (Flint et al., 1993). Studies of variation not accounting for obvious functional differences have been taken up by biological anthropologists.