Box 2. Emerging understanding of human genetic diversity

From the following article:

Let's celebrate human genetic diversity

Bruce T. Lahn & Lanny Ebenstein

Nature 461, 726-728(8 October 2009)



Genetic diversity is the differences in DNA sequence among members of a species. It is present in all species owing to the interplay of mutation, genetic drift, selection and population structure. When a species is reproductively isolated into multiple groups by geography or other means, the groups differentiate over time in their average genetic make-up.

Anatomically modern humans first appeared in eastern Africa about 200,000 years ago. Some members migrated out of Africa by 50,000 years ago to populate Asia, Australia, Europe and eventually the Americas9. During this period, geographic barriers separated humanity into several major groups, largely along continental lines, which greatly reduced gene flow among them. Geographic and cultural barriers also existed within major groups, although to lesser degrees.

This history of human demography, along with selection, has resulted in complex patterns of genetic diversity. The basic unit of this diversity is polymorphisms — specific sites in the genome that exist in multiple variant forms (or alleles). Many polymorphisms involve just one or a few nucleotides, but some may involve large segments of genetic material2. The presence of polymorphisms leads to genetic diversity at the individual level such that no two people's DNA is the same, except identical twins. The alleles of some polymorphisms are also found in significantly different frequencies among geographic groups1, 5. An extreme example is the pigmentation gene SLC24A5. An allele of SLC24A5 that contributes to light pigmentation is present in almost all Europeans but is nearly absent in east Asians and Africans10.

Given these geographically differentiated polymorphisms, it is possible to group humans on the basis of their genetic make-up. Such grouping largely confirms historical separation of global populations by geography5. Indeed, a person's major geographic group identity can be assigned with near certaintly on the basis of his or her DNA alone (now an accepted practice in forensics). There is growing evidence that some of the geographically differentiated polymorphisms are functional, meaning that they can lead to different biological outcomes (just how many is the subject of ongoing research). These polymorphisms can affect traits such as pigmentation, dietary adaptation and pathogen resistance (where evidence is rather convincing)10, 11, 12, and metabolism, physical development and brain biology (where evidence is more preliminary)6, 8, 13, 14.

For most biological traits, genetically based differentiation among groups is probably negligible compared with the variation within the group. For other traits, such as pigmentation and lactose intolerance, differences among groups are so substantial that the trait displays an inter-group difference that is non-trivial compared with the variance within groups, and the extreme end of a trait may be significantly over-represented in a group.

Several studies have shown that many genes in the human genome may have undergone recent episodes of positive selection — that is, selection for advantageous biological traits6. This is contrary to the position advocated by some scholars that humans effectively stopped evolving 50,000–40,000 years ago15. In general, positive selection can increase the prevalence of functional polymorphisms and create geographic differentiation of allele frequencies.

B.T.L. & L.E.