EVOLUTION

Heim and Meyer indicated that the CYP2D cluster on chromosome 22 contains the functional gene

CYP2D6 and 2 or 3 highly homologous pseudogenes. To understand the evolutionary sequence of

mutational events as well as the interracial differences, they analyzed the arrangement of the CYP2D

haplotype containing a common mutant allele of CYP2D6 associated with an XbaI 44-kb restriction

fragment. This haplotype was found to contain 4 CYP2D genes instead of 3. Comparison of the sequences

of these genes with those of previously characterized haplotypes suggested that an early point mutation

was followed by a crossover and a gene conversion event, the latter found preferentially in Caucasians.

The data were considered consistent with the rapid evolution of the CYP2D 'locus' during 'plant-animal

warfare' with practical consequences for present-day defense against environmental adversity. Kimura et

al. suggested that these enzymes evolved to metabolize plant toxins; since current human diets rely almost

totally on cultivation,while early man was a hunter-gatherer, the genes may now be in the process of being

lost. Gene conversion events involving the closely linked and similar CYP2D7 and CYP2D8P genes may

hasten this process.