Home > Technical section > Biology > Molecular biology > Population genetics > gene selection
gene selection
Friday 30 September 2005
The earliest evidence of selection acting on a human gene was the discovery that heterozygotes of the hemoglobin A/S polymorphism have greater resistance to malaria than do AA or SS homozygotes.
In malarial environments, this results in a balanced polymorphism that maintains the S allele even though SS individuals are severely ill with sickle-cell anemia.
Recent studies of DNA variation have focused on detecting signatures of selection, either balancing selection or directional selection. This has produced many different statistical tests using DNA diversity, and comparisons of nucleotide substitutions that do or do not affect the amino acid sequence of proteins.
Blancing selection
Strong molecular evidence of balancing selection, also in malarial environments, has been found for the G6PD locus, the low-activity alleles of which seem to confer resistance to malaria.
Other analyses have found evidence for positive selection at both G6PD and another gene TNFSF5, which is also implicated in the response to infectious agents.
Directional selection
Strong directional selection has also been proposed for FOXP2, which shows a two amino-acid difference between the human protein and the monomorphic form in primates.
It has been suggested that these changes may have been selectively important for the evolution of speech and language in modern humans.
In other genes, however, the agent of selection is not at all obvious; for example, the CCR5 gene seems to be related to HIV resistance, and mutations in the BRCA1 gene produce an increased risk of female breast cancer.
In such cases it is often very difficult to disentangle the effects of population dynamics or structure from selective pressures.
These complications can be clearly observed in a thorough analysis of the HFE locus, mutations of which result in hemochromatosis. In this study no evidence of selection on single SNPs or on haplotypes was detected, but significant between-continent variation was found. Unlike other studies, African samples showed only slightly more rare SNPs than Europeans or Asians. This suggests the possibility that different evolutionary models are relevant to the different continents.
References
Cavalli-Sforza LL, Feldman MW. The application of molecular genetic approaches to the study of human evolution. Nat Genet. 2003 Mar;33 Suppl:266-75. PMID: 12610536