Immunogenetics as a tool in anthropological studies

Abstract

The genes coding for the main molecules involved in the human immune system--immunoglobulins, human leucocyte antigen (HLA) molecules and killer-cell immunoglobulin-like receptors (KIR)--exhibit a very high level of polymorphism that reveals remarkable frequency variation in human populations. 'Genetic marker' (GM) allotypes located in the constant domains of IgG antibodies have been studied for over 40 years through serological typing, leading to the identification of a variety of GM haplotypes whose frequencies vary sharply from one geographic region to another. An impressive diversity of HLA alleles, which results in amino acid substitutions located in the antigen-binding region of HLA molecules, also varies greatly among populations. The KIR differ between individuals according to both gene content and allelic variation, and also display considerable population diversity. Whereas the molecular evolution of these polymorphisms has most likely been subject to natural selection, principally driven by host-pathogen interactions, their patterns of genetic variation worldwide show significant signals of human geographic expansion, demographic history and cultural diversification. As current developments in population genetic analysis and computer simulation improve our ability to discriminate among different--either stochastic or deterministic--forces acting on the genetic evolution of human populations, the study of these systems shows great promise for investigating both the peopling history of modern humans in the time since their common origin and human adaptation to past environmental (e.g. pathogenic) changes. Therefore, in addition to mitochondrial DNA, Y-chromosome, microsatellites, single nucleotide polymorphisms and other markers, immunogenetic polymorphisms represent essential and complementary tools for anthropological studies.

Figure 1

Multidimensional scaling analysis (MDS) of 82 populations from all continents tested for the GM polymorphism. Each point represents a population and its symbol its geographic region. Populations are arranged in a three-dimensional space that best reproduces the observed genetic distances. The orientations of the axes are arbitrary, and their scales are relative to each other. The fit to the original genetic distance matrix is measured by a Stress value (from 0.4 = poor to 0.0 = perfect). Data are from Dugoujon et al. (2004). Stress value = 0.158 (good).

Figure 2

New HLA nomenclature system adopted in 2010 (Figure kindly provided by S.G.E. Marsh, HLA Informatics Group, http://hla.alleles.org/nomenclature/naming.html). Note that the gene symbols are written in italics, in contrast to the gene products which are not italicized.

Figure 3

Multidimensional scaling analysis (MDS) of 39 populations from East Asia tested for HLA (average distances were computed on HLA-A, HLA-B and HLA-DRB1 data). Each point represents a population and its symbol the linguistic family to which its language belongs. Stress value = 0.10 (good).

Figure 4

KIR haplotypes have variable gene content. Map of selected KIR haplotypes is shown. Haplotype 1 represents group-A KIR haplotype and the remainder are the representative of over 30 known group-B haplotypes. The framework genes, present in all haplotypes are shown in black boxes; genes encoding activating KIR are in gray boxes; and those for inhibitory receptors are in white boxes. KIR2DP1 and KIR3DP1 are pseudogenes that do not encode any functional receptors.