Magnus Nordborg

The effects of local selection, balanced polymorphism and background selection on equilibrium patterns of genetic diversity in subdivided populations.

Levels of neutral genetic diversity in populations subdivided into two demes were studied by multilocus stochastic simulations. The model includes deleterious mutations at loci throughout the genome, causing background selection, as well as a single locus at which a polymorphism is maintained, either by frequency-dependent selection or by local selective differences. These balanced polymorphisms induce long coalescence times at linked neutral loci, so that sequence diversity at these loci is enhanced at statistical equilibrium. We study how equilibrium neutral diversity levels are affected by the degree of population subdivision, the presence or absence of background selection, and the level of inbreeding of the population. The simulation results are compared with approximate analytical formulae, assuming the infinite sites neutral model. We discuss how balancing selection can be distinguished from local selection, by determining whether peaks of diversity in the region of the polymorphic locus are seen within or between demes. The width of such diversity peaks is shown to depend on the total species population size, rather than local deme sizes. We show that, with population subdivision, local selection enhances between-deme diversity even at neutral sites distant from the polymorphic locus, producing higher FST values than with no selection; very high values can be generated at sites close to a selected locus. Background selection also increases FST, mainly because of decreased diversity within populations, which implies that its effects may be distinguishable from those of local selection. Both effects are stronger in selfing than outcrossing populations. Linkage disequilibrium between neutral sites is generated by both balancing and local selection, especially in selfing populations, because of linkage disequilibrium between the neutral sites and the selectively maintained alleles. We discuss how these theoretical results can be related to data on genetic diversity within and between local populations of a species.

The effect of recombination on background selection

An approximate equation is derived, which predicts the effect on variability at a neutral locus of background selection due to a set of partly linked deleterious mutations. Random mating, multiplicative fitnesses, and sufficiently large population size that the selected loci are in mutation/selection equilibrium are assumed. Given these assumptions, the equation is valid for an arbitrary genetic map, and for an arbitrary distribution of selection coefficients across loci. Monte Carlo computer simulations show that the formula performs well for small population sizes under a wide range of conditions, and even seems to apply when there are epistatic fitness interactions among the selected loci. Failure occurred only with very weak selection and tight linkage. The formula is shown to imply that weakly selected mutations are more likely than strongly selected mutations to produce regional patterning of variability along a chromosome in response to local variation in recombination rates. Loci at the extreme tip of a chromosome experience a smaller effect of background selection than loci closer to the centre. It is shown that background selection can produce a considerable overall reduction in variation in organisms with small numbers of chromosomes and short maps, such as Drosophila. Large overall effects are less likely in species with higher levels of genetic recombination, such as mammals, although local reductions in regions of reduced recombination might be detectable.

On the probability of Neanderthal ancestry.

I thank B. Bengtsson, A. Di Rienzo, P. Donnelly, R. Harding, the reviewers, and especially T. Nagylaki, for their comments on the manuscript. This work was supported by the Erik Philip-Sorensen Foundation.

The effect of seed and rosette cold treatment on germination and flowering time in some Arabidopsis thaliana (Brassicaceae) ecotypes.

The germination and flowering responses to cold treatment were investigated in 32 ecotypes of Arabidopsis thaliana. A month-long cold treatment at the seed stage decreased the time until flowering in all but one strain, whereas a 3-d cold treatment had little, or the opposing effect. A month-long cold treatment at the rosette stage also decreased the time until flowering, but was less effective than seed cold treatment. Seed and rosette cold treatments did not have an additive effect on time until flowering. Cold treatment usually increased the speed of germination, however no clear response patterns for the probability of germination were detected. These findings are discussed in relation to the life cycle of the plant.

Increased Levels of Polymorphism Surrounding Selectively Maintained Sites in Highly Selfing Species

If selection maintains polymorphism at a site, an increase of neutral variability in the surrounding region is expected, because sites closely linked to alternative alleles at the selected site accumulate mutations as if they were in different populations. Selection thus creates a signal of increased polymorphism relative to the background noise of neutral polymorphism. We show, by a theoretical study, that the effects of balanced polymorphisms on variability are highly localized in inbreeding populations, and that the overall level of variability is strongly reduced by selection against deleterious mutations. This implies that the signals of balancing selection are much stronger than in outcrossing populations.