Schierup MH, Mikkelsen AM, Hein J. Recombination, balancing selection and phylogenies in MHC and self-incompatibility genes. Genetics 159: 1833-1844

Bioinformatics Research Center (BiRC), Department of Ecology and Genetics, University of Aarhus, 8000 Aarhus C., Denmark.
Genetics (Impact Factor: 5.96). 01/2002; 159(4):1833-44.
Source: PubMed


Using a coalescent model of multiallelic balancing selection with recombination, the genealogical process as a function of recombinational distance from a site under selection is investigated. We find that the shape of the phylogenetic tree is independent of the distance to the site under selection. Only the timescale changes from the value predicted by Takahata's allelic genealogy at the site under selection, converging with increasing recombination to the timescale of the neutral coalescent. However, if nucleotide sequences are simulated over a recombining region containing a site under balancing selection, a phylogenetic tree constructed while ignoring such recombination is strongly affected. This is true even for small rates of recombination. Published studies of multiallelic balancing selection, i.e., the major histocompatibility complex (MHC) of vertebrates, gametophytic and sporophytic self-incompatibility of plants, and incompatibility of fungi, all observe allelic genealogies with unexpected shapes. We conclude that small absolute levels of recombination are compatible with these observed distortions of the shape of the allelic genealogy, suggesting a possible cause of these observations. Furthermore, we illustrate that the variance in the coalescent with recombination process makes it difficult to locate sites under selection and to estimate the selection coefficient from levels of variability.

Full-text preview

Available from:
  • Source
    • "An equivalent phenomenon can be observed in absence of contemporary gene flow, when ancestral polymorphisms have been maintained during past speciation events (Avise and Robinson 2008; Fig. 1B). Known examples of incomplete lineage sorting of adaptive significance mostly include alleles under long-term balancing selection such as in plant / plant pathogen recognition systems (Stahl et al. 1999; Rose et al. 2007; Horger et al. 2012), major histocompatibility complexes in mammals (Edwards et al. 1997; Loisel et al. 2006), AB-blood type defining enzymes and viral response factors in primates (Newman et al. 2006; Ferrer-Admetlla et al. 2009; Segurel et al. 2012), photoreceptors sustaining color vision in New World monkeys (Hunt et al. 1998), and self-incompatibility genes in plants and fungi (Wu et al. 1998; Schierup et al. 2001; Charlesworth et al. 2006; Igic et al. 2006). The recent development of methods dedicated to the detection of ancestral polymorphisms should yield to better estimates of the frequency of this phenomenon (Scally et al. 2012; Segurel et al. 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: What is the nature of the genetic changes underlying phenotypic evolution? We have catalogued 1008 alleles described in the literature that cause phenotypic differences among animals, plants, and yeasts. Surprisingly, evolution of similar traits in distinct lineages often involves mutations in the same gene ("gene reuse"). This compilation yields three important qualitative implications about repeated evolution. First, the apparent evolution of similar traits by gene reuse can be traced back to two alternatives, either several independent causative mutations or a single original mutational event followed by sorting processes. Second, hotspots of evolution-defined as the repeated occurrence of de novo mutations at orthologous loci and causing similar phenotypic variation-are omnipresent in the literature with more than 100 examples covering various levels of analysis, including numerous gain-of-function events. Finally, several alleles of large effect have been shown to result from the aggregation of multiple small-effect mutations at the same hotspot locus, thus reconciling micromutationist theories of adaptation with the empirical observation of large-effect variants. Although data heterogeneity and experimental biases prevented us from extracting quantitative trends, our synthesis highlights the existence of genetic paths of least resistance leading to viable evolutionary change.
    Full-text · Article · May 2013 · Evolution
  • Source
    • "Recombination would break up the association between pollen and pistil self-incompatibility loci, and thus is predicted to be suppressed around SI loci (Stein et al., 1991). Little evidence for recombination exists in gametophytic systems (Schierup et al., 2001), but this result may be due to the lack of power of recombination-detecting statistics, caused by the extraordinarily high polymorphism at these loci. Several successive mutations have occurred at the majority of segregating sites in these loci; this shows that mutation creates variation, but it also obscures the role of recombination. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Allorecognition is the ability of an organism to differentiate self or close relatives from unrelated conspecifics. Effective allorecognition systems are critical to the survival of organisms; they prevent inbreeding and facilitate fusions between close relatives. Where the loci governing allorecognition outcomes have been identified, the corresponding proteins often exhibit exceptional polymorphism. Two important questions about this polymorphism remain unresolved: how is it created, and how is it maintained. Because the genetic bases of several allorecognition systems have now been identified, including alr1 and alr2 in Hydractinia, fusion histocompatibility in Botryllus, the het (vic) loci in fungi, tgrB1 and tgrC1 in Dictyostelium, and self-incompatibility (SI) loci in several plant families, we are now poised to achieve a clearer understanding of how these loci evolve. In this review, we summarize what is currently known about the evolution of allorecognition loci, highlight open questions, and suggest future directions.
    Full-text · Article · Dec 2011 · Frontiers in Immunology
  • Source
    • "There is some evidence for existence of sheltered load (Stone 2004; Llaurens et al. 2009). Second, Schierup et al. (2001) proposed that recombination could explain long terminal branches, by creating haplotypes whose sequences are composed of fragments with different evolutionary histories, thus homogenizing sequence divergence among them. Recombination may occur among SI haplotypes in Arabidopsis (Castric et al. 2010), Petunia inflata (Wang et al. 2001), Prunus dulcis (Ortega et al. 2006), and other Solanaceae and Rosaceae (Vieira et al. 2003). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Self-incompatibility (SI) is a genetic system found in some hermaphrodite plants. Recognition of pollen by pistils expressing cognate specificities at two linked genes leads to rejection of self pollen and pollen from close relatives, i.e., to avoidance of self-fertilization and inbred matings, and thus increased outcrossing. These genes generally have many alleles, yet the conditions allowing the evolution of new alleles remain mysterious. Evolutionary changes are clearly necessary in both genes, since any mutation affecting only one of them would result in a nonfunctional self-compatible haplotype. Here, we study diversification at the S-locus (i.e., a stable increase in the total number of SI haplotypes in the population, through the incorporation of new SI haplotypes), both deterministically (by investigating analytically the fate of mutations in an infinite population) and by simulations of finite populations. We show that the conditions allowing diversification are far less stringent in finite populations with recurrent mutations of the pollen and pistil genes, suggesting that diversification is possible in a panmictic population. We find that new SI haplotypes emerge fastest in populations with few SI haplotypes, and we discuss some implications for empirical data on S-alleles. However, allele numbers in our simulations never reach values as high as observed in plants whose SI systems have been studied, and we suggest extensions of our models that may reconcile the theory and data.
    Full-text · Article · Apr 2011 · Genetics
Show more