Introduction: from immunology to anthropology
More than a century has elapsed since the discovery of the ABO blood groups in 1900 by Karl Landsteiner through haemagglutination assays, (see ref. 1 for a review) an event that marked the starting point of immunogenetic studies applied to the analysis of genetic variation in humans. Other antigens of the red blood cells (together with allozymes, through electrophoretic techniques) were successively found and studied in human populations during the first half of the 20th century.2 Molecules that are instrumental in the immune responses of human beings also revealed inter-individual differences such as immunoglobulins, with the discovery of allotypic variation,3,4 and human leucocyte antigen (HLA) molecules,5 with the finding of an unexpectedly high degree of polymorphism at the level of their peptide-binding region (see http://www.ebi.ac.uk/imgt/hla/). Killer-cell immunoglobulin-like receptors (KIR) were also shown to exhibit a complex polymorphism where both the number of alleles and the number of genes may vary among individuals.6
Today, almost 350 severe pathogens are registered on a worldwide scale (Gideon online. Retrieved from http://www.gideononline.com on 20 December 2010) and many others have existed and are now extinct. Each year, seasonal epidemics of influenza remind us that the turnover of most viruses is very rapid. A high level of polymorphism in the genes coding for molecules involved in immune responses is therefore not surprising in light of our exposure to such a diversity of infectious agents, because we know that evolution may easily adapt the genetic pool of populations to specific environmental pressures through natural selection. For example, red blood cell antigens were found to act as receptors for a number of pathogens, (e.g. Plasmodium vivax, for FY, Plasmodium falciparum, for GPA, Toxoplasma gondii, for RH), and hence to play an important role in the susceptibility or resistance of our organism against specific diseases. In the case of FY, the null allele was positively selected in some geographic regions, but not in others, allowing red blood cells to escape P. vivax infection.7 Also, HLA allelic variation may have been maintained through heterozygote advantage, because we know that some HLA alleles are associated with resistance to several fatal diseases, one recent example being the association of HLA-B*27, HLA-B*51 and HLA-B*57 with improved prognosis of AIDS.8
On the other hand, since the very beginning of population genetic applications of such polymorphisms it was observed that their worldwide patterns of genetic diversity tended to exhibit a geographic structure. Population trees generally discriminated populations from different continents, the main controversy being the position of Africans, either segregating with Europeans within an ‘occidental group’ separated from an ‘oriental group’ of Asian, Amerindian and Oceanian populations,9 or segregating separately from the others.10 This observation indicates that natural selection was probably not the only mechanism at work in the evolution of these polymorphisms, but that their patterns of genetic diversity were also shaped by the history of human migrations; hence the increasing interest in using these immunogenetic systems as informative tools to reconstruct human peopling history. Now, after several decades during which researchers have accumulated population data for these polymorphisms and have analysed their variation at different geographic scales, we may ask whether such studies are indeed useful for anthropological research.
The present review summarizes our current knowledge of three major immunogenetic systems, GM, HLA and KIR, in relation to human population diversity studies. These three polymorphisms symbolize the past (GM), present (HLA) and future (KIR) of immunogenetic studies applied to anthropology, both because different typing technologies have been used to analyse their variability (serology for GM; both serology and molecular typing for HLA; and molecular typing for KIR), and because for each system, our understanding of its diversity in human populations is at a different stage (comprehensive for GM; still increasing for HLA; and just starting for KIR). On the other hand, because the three polymorphisms are encoded by independent regions of our genome, are expressed by different kinds of molecules, and are studied in different sets of populations, they provide complementary information for anthropological studies.