The effects of multilocus balancing selection on neutral variability.
We studied the effect of multilocus balancing selection on neutral nucleotide variability at linked sites by simulating a model where diallelic polymorphisms are maintained at an arbitrary number of selected loci by means of symmetric overdominance. Different combinations of alleles define different genetic backgrounds that subdivide the population and strongly affect variability. Several multilocus fitness regimes with different degrees of epistasis and gametic disequilibrium are allowed. Analytical results based on a multilocus extension of the structured coalescent predict that the expected linked neutral diversity increases exponentially with the number of selected loci and can become extremely large. Our simulation results show that although variability increases with the number of genetic backgrounds that are maintained in the population, it is reduced by random fluctuations in the frequencies of those backgrounds and does not reach high levels even in very large populations. We also show that previous results on balancing selection in single-locus systems do not extend to the multilocus scenario in a straightforward way. Different patterns of linkage disequilibrium and of the frequency spectrum of neutral mutations are expected under different degrees of epistasis. Interestingly, the power to detect balancing selection using deviations from a neutral distribution of allele frequencies seems to be diminished under the fitness regime that leads to the largest increase of variability over the neutral case. This and other results are discussed in the light of data from the Mhc.
Navarro
Arcadio
A
Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom. arcadi@holyrood.ed.ac.uk
Barton
Nick H
NH
D003198:Computer Simulation; D004843:Epistasis, Genetic; D005787:Gene Frequency; D014644:Genetic Variation; D006579:Heterozygote; D012641:Selection, Genetic