Evolution__3rd_Edition

204 PART 2 / Evolutionary Genetics
Centromere
Class II Class III Class I
DP DZ DO DX DQ DR
β α β α α β β α β α β β β α
1,000 kb
Figure 8.3
Genetic map of the human HLA loci on chromosome 6.
The text concentrates on the A and B loci, but there are many
Linkage disequilibrium exists
between some HLA loci
Complement
proteins
Cytokines
TNF LT B C A
Class I-like
more genes in the histocompatibility system (not drawn
exactly to scale).
HIV. The full diversity of HLA types may reflect a history of coevolution between
humans and disease agents. Disease agents may have tried to fool the immune system
into treating the agent as part of the body, and the human population would then
respond over evolutionary time by evolving new HLA alleles as new, reliable indicators
of “self.” This would provide a further advantage to variability in the HLA loci. A heterozygous
individual with two HLA proteins can compare itself with a possible invader in
two ways: the invader has to match a homozygote only in one respect, but a heterozygote
has to be matched in two independent respects. The HLA loci therefore probably show
heterozygous advantage (Section 5.12, p. 123), and the same process may have caused
the exceptional pattern of evolution in silent and amino acid-changing bases within
codon triplets (Section 7.8.2, p. 182).
The HLA system also provides examples of linkage disequilibrium. Particular combinations
of genes are found in greater than random proportions. In North European
populations, there is characteristically an excess of the A 1 B 8 haplotype. Figure 8.4a is a
more general picture. It shows the linkage disequilibrium values for all combinations of
B alleles and the allele A 1 . There could be an analogous graph for each A allele. In Figure
8.4a, D = 0.07 for A 1 B 8 . If A 1 and B 8 combined in their population proportions, A 1 B 8
would have a frequency of about 0.023 (2.3%); but in fact it is found in about 9.3% of
individuals (0.093 − 0.023 = D = 0.07). In all, the HLA-A and -B loci have about six clear
cases of linkage disequilibrium; A 1 B 8 and A 3 B 7 are the most striking. The reason why
these haplotypes are found in greater than random proportions is unknown, though
it is generally believed to be due to selection in favor of the gene combinations. But
selection is not the only possible reason for linkage disequilibrium, as the next section
will reveal.
8.7 Linkage disequilibrium can exist for several reasons
Recombination breaks down non-random genic associations, and yet in some cases
like Papilio memnon and the HLA genes, non-random associations exist. What is
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