A large case-control study of malaria in West African children shows that a human leucocyte class I antigen (HLA-Bw53) and an HLA class II haplotype (DRB1*1302-DQB1*0501), common in West Africans but rare in other racial groups, are independently associated with protection from severe malaria. In this population they account for as great a reduction in disease incidence as the sickle-cell haemoglobin variant. These data support the hypothesis that the extraordinary polymorphism of major histocompatibility complex genes has evolved primarily through natural selection by infectious pathogens.

/pdf/common-west-african-hla-antigens-are-associated-with-22igsgshrl.pdf

Common West African HLA antigens are associated with protection from severe malaria

Darwinian theory has yet to explain adequately the fact of sex. If males provide little or no aid to offspring, a high (up to 2-fold) extra average fitness has to emerge as a property of a sexual parentage if sex is to be stable. The advantage must presumably come from recombination but has been hard to identify. It may well lie in the necessity to recombine defenses to defeat numerous parasites. A model demonstrating this works best for contesting hosts whose defense polymorphisms are constrained to low mutation rates. A review of the literature shows that the predictions of parasite coevolution fit well with the known ecology of sex. Moreover, parasite coevolution is superior to previous models of the evolution of sex by supporting the stability of sex under the following challenging conditions: very low fecundity, realistic patterns of genotype fitness and changing environment, and frequent mutation to parthenogenesis, even while sex pays the full 2-fold cost.

https://www.pnas.org/content/pnas/87/9/3566.full.pdf

Sexual reproduction as an adaptation to resist parasites (a review)

Until around 1990, most multigene families were thought to be subject to concerted evolution, in which all member genes of a family evolve as a unit in concert. However, phylogenetic analysis of MHC and other immune system genes showed a quite different evolutionary pattern, and a new model called birth-and-death evolution was proposed. In this model, new genes are created by gene duplication and some duplicate genes stay in the genome for a long time, whereas others are inactivated or deleted from the genome. Later investigations have shown that most non-rRNA genes including highly conserved histone or ubiquitin genes are subject to this type of evolution. However, the controversy over the two models is still continuing because the distinction between the two models becomes difficult when sequence differences are small. Unlike concerted evolution, the model of birth-and-death evolution can give some insights into the origins of new genetic systems or new phenotypic characters.

/pdf/concerted-and-birth-and-death-evolution-of-multigene-59ik8yal3k.pdf

Concerted and birth-and-death evolution of multigene families.

Elucidating how natural selection promotes local adaptation in interaction with migration, genetic drift and mutation is a central aim of evolutionary biology. While several conceptual and practical limitations are still restraining our ability to study these processes at the DNA level, genes of the major histocompatibility complex (MHC) offer several assets that make them unique candidates for this purpose. Yet, it is unclear what general conclusions can be drawn after 15 years of empirical research that documented MHC diversity in the wild. The general objective of this review is to complement earlier literature syntheses on this topic by focusing on MHC studies other than humans and mice. This review first revealed a strong taxonomic bias, whereby many more studies of MHC diversity in natural populations have dealt with mammals than all other vertebrate classes combined. Secondly, it confirmed that positive selection has a determinant role in shaping patterns of nucleotide diversity in MHC genes in all vertebrates studied. Yet, future tests of positive selection would greatly benefit from making better use of the increasing number of models potentially offering more statistical rigour and higher resolution in detecting the effect and form of selection. Thirdly, studies that compared patterns of MHC diversity within and among natural populations with neutral expectations have reported higher population differentiation at MHC than expected either under neutrality or simple models of balancing selection. Fourthly, several studies showed that MHC-dependent mate preference and kin recognition may provide selective factors maintaining polymorphism in wild outbred populations. However, they also showed that such reproductive mechanisms are complex and context-based. Fifthly, several studies provided evidence that MHC may significantly influence fitness, either by affecting reproductive success or progeny survival to pathogens infections. Overall, the evidence is compelling that the MHC currently represents the best system available in vertebrates to investigate how natural selection can promote local adaptation at the gene level despite the counteracting actions of migration and genetic drift. We conclude this review by proposing several directions where future research is needed.

/pdf/mhc-studies-in-nonmodel-vertebrates-what-have-we-learned-d92b9hevn5.pdf

MHC studies in nonmodel vertebrates: what have we learned about natural selection in 15 years?

▪ Abstract Molecular clocks have profoundly influenced modern views on the timing of important events in evolutionary history. We review recent advances in estimating divergence times from molecular data, emphasizing the continuum between processes at the phylogenetic and population genetic scales. On the phylogenetic scale, we address the complexities of DNA sequence evolution as they relate to estimating divergences, focusing on models of nucleotide substitution and problems associated with among-site and among-lineage rate variation. On the population genetic scale, we review advances in the incorporation of ancestral population processes into the estimation of divergence times between recently separated species. Throughout the review we emphasize new statistical methods and the importance of model testing during the process of divergence time estimation.

/pdf/estimating-divergence-times-from-molecular-data-on-ofdocyxapt.pdf

Estimating Divergence Times from Molecular Data on Phylogenetic and Population Genetic Timescales

Two features distinguish the polymorphism of the major histocompatibility complex (MHC) loci from that of other loci: its high diversity and the large genetic distance between MHC alleles. More than 100 alleles exist in natural populations in the mouse at each of the functional class I and class II alleles, all alleles occurring at frequencies that cannot be explained by recurrent mutations. Some of the alleles differ by approximately 70 nucleotides in the coding region alone and some of the products of the allelic genes differ by more than 50 amino acids. It has generally been assumed that these differences accumulated after species inception. Here, we present evidence for an alternative explanation of the origin of MHC polymorphism: a large part of the MHC polymorphism pre-dates speciation and is passed on from species to species. We describe allelic differences that must have arisen before the separation of mice and rats from a common ancestor more than 10 million years ago.

Eberhardt Gúnther

Papers

MHC polymorphism pre-dating speciation.