multilocus balancing selection

Navarro A & Barton NH 2002 The effects of multilocus balancing selection on neutral viability. Genetics 161:849-863.

  • forward simulations are probably the most straightforward method (Barton & Navarro 2002)
  • we aim to focus on qualitative results that will not depend on the exact nature of selection or on the details of the model
  • the main factors influencing the degree of polymorphism and linkage disequilibrium at the selected loci are, together with recombination and population size, the strength and nature of selection
  • the amount of linkage disequilibrium in the system is an important issue
  • because it determine the actual degree of subdivision in the population
  • the results ... (with low recombination) become clear if one considers that the population depicted there consists essentially of two complementary background, independently of the number of selected loci
  • one needs only to recalculate the coalescent predictions, taking into account the real background equilibrium frequencies
  • when recombination is low, nondominant backgrounds have such low frequencies that most of the time they are absent from the population and, thus, can be ignored
  • with intermediate or high recombination one needs to take into account the exact equilibrium frequencies in the coalescent
  • the helpful assumption made by Barton and Navarro (2002) of no linkage disequilibrium between selected loci cannot be used
  • independently of the number of loci and the selection regime, neutral variability does not increase for markers at at extreme of the set of selected loci when Nr > 1
  • as expected, simulated and predicted results diverge when the number of loci is large
  • independently of this discrepancy, the effect of the set of selected loci on neutral variability dissipates when recombination between them and the neutral locus is > 1 / N
  • chromosomal regions between selected loci
  • negative epistasis and intermediate or low recombination (r ≥ 10− 3, Figure 7a)
  • maximum neutral variability (which is always found in regions closely linked to the selected loci) is increased beyond the one-locus (two backgrounds) limit
  • the population is more subdivided with two loci (four backgrounds) than with a single one
  • variability is increased in a wider region of the chromosome than expected for a single locus alone
  • still, high recombination rates (r > 10− 3) preclude any relevant multilocus effect and the predicted values are almost identical for one as for two selected loci
  • Figure 7b
  • multiplicative fitnesses
  • results for positive epistasis (not shown) are qualitatively equivalent
  • variability is not increased beyond the one-locus limit because the population is dominated by only two backgrounds
  • in segments between selected loci, however, a second kind of multilocus effect is detected
  • crossing over between the two selected loci, which would allow neutral alleles to recombine away, breaks linkage disequilibrium and generates gametes that are eliminated by selection
  • the effective recombination rate is reduced in regions between selected loci
  • if selection is strong enough, variability can be increased even when recombination is high
  • Figure 8b with r = 10− 2
  • the extended coalescent needs only information about the frequencies of the selectively relevant haplotypes and not about the kind of selection producing them
  • diversity is enhanced at neutral markers located in regions among the set
  • even if they are a long way from the selected loci themselves
  • Figure 8 with r = 10− 2, Nr = 10
  • this mechanism has been already described by Kelly and Wade (2000)
  • who analyzed a system formed by two diallelic, epistatically interacting loci and obtained predictions for the patterns of neutral sequence variation linked to them
  • their model is an instance of the positive epistasis scenario presented here