Defining and interpreting intraspecific molecular variation.

Defining the extent and character of intraspecific genetic variation provides important information about gene function and organismal history. Powerful tests may be applied to sequenced alleles in order to critically examine whether natural selection is responsible for limiting or elevating intraspecific polymorphism in particular genes. Unconventional patterns of sequence variation and unusual allelic frequency distributions can be used to test whether genes encoding parasite antigens are being diversified by immune selection. The strikingly limited genetic variation in the falciparum malaria genome, and in human chromosomes encoding resistance to severe malaria, date the emergence of this disease to within the last few thousand years, illustrating the power of population genetic analysis to elucidate the history of host-parasite interactions. Coupling phylogenetic and geographic information and analyzing the rate of diversification in intraspecific gene trees provides new and rich sources of information on microbial evolution and epidemiology.