Selection & the innate immune system

By Razib Khan | April 10, 2009 10:22 am

Signatures of natural selection are not uniform across genes of innate immune system, but purifying selection is the dominant signature:

We tested the opposing views concerning evolution of genes of the innate immune system that (i) being evolutionary ancient, the system may have been highly optimized by natural selection and therefore should be under purifying selection, and (ii) the system may be plastic and continuing to evolve under balancing selection. We have resequenced 12 important innate-immunity genes (CAMP, DEFA4, DEFA5, DEFA6, DEFB1, MBL2, and TLRs 1, 2, 4, 5, 6, and 9) in healthy volunteers (n = 171) recruited from a region of India with high microbial load. We have compared these data with those of European-Americans (EUR) and African-Americans (AFR). We have found that most of the human haplotypes are many mutational steps away from the ancestral (chimpanzee) haplotypes, indicating that humans may have had to adapt to new pathogens. The haplotype structures in India are significantly different from those of EUR and AFR populations, indicating local adaptation to pathogens. In these genes, there is (i) generally an excess of rare variants, (ii) high, but variable, degrees of extended haplotype homozygosity, (iii) low tolerance to nonsynonymous changes, (iv) essentially one or a few high-frequency haplotypes, with star-like phylogenies of other infrequent haplotypes radiating from the modal haplotypes. Purifying selection is the most parsimonious explanation operating on these innate immunity genes. This genetic surveillance system recognizes motifs in pathogens that are perhaps conserved across a broad range of pathogens. Hence, functional constraints are imposed on mutations that diminish the ablility of these proteins to detect pathogens.

Purifying selection presumably suggests that the variants on many of these genes are fitness optimized, as new variants are quickly removed from the population due to their low fitness. Nevertheless the differences between populations, and form chimps, would indicate periodic pulses of positive selection fixing new favorable variants.

CATEGORIZED UNDER: Evolution, Genetics
  • Fly

    re: Selection signature
    Biologists Discover How ‘Silent’ Mutations Influence Protein Production
    “synonymous mutations determine mRNA folding and thereby the eventual protein level”


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About Razib Khan

I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. In relation to nationality I'm a American Northwesterner, in politics I'm a reactionary, and as for religion I have none (I'm an atheist). If you want to know more, see the links at


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