Linkage Disequilibrium Under Recurrent Bottlenecks
Artikel i vetenskaplig tidskrift, 2012

To model deviations from selectively neutral genetic variation caused by different forms of selection, it is necessary to first understand patterns of neutral variation. Best understood is neutral genetic variation at a single locus. But, as is well known, additional insights can be gained by investigating multiple loci. The resulting patterns reflect the degree of association (linkage) between loci and provide information about the underlying multilocus gene genealogies. The statistical properties of two-locus gene genealogies have been intensively studied for populations of constant size, as well as for simple demographic histories such as exponential population growth and single bottlenecks. By contrast, the combined effect of recombination and sustained demographic fluctuations is poorly understood. Addressing this issue, we study a two-locus Wright-Fisher model of a population subject to recurrent bottlenecks. We derive coalescent approximations for the covariance of the times to the most recent common ancestor at two loci in samples of two chromosomes. This covariance reflects the degree of association and thus linkage disequilibrium between these loci. We find, first, that an effective population-size approximation describes the numerically observed association between two loci provided that recombination occurs either much faster or much more slowly than the population-size fluctuations. Second, when recombination occurs frequently between but rarely within bottlenecks, we observe that the association of gene histories becomes independent of physical distance over a certain range of distances. Third, we show that in this case, a commonly used measure of linkage disequilibrium, sigma(2)(d) (closely related to (r) over cap (2)), fails to capture the long-range association between two loci. The reason is that constituent terms, each reflecting the long-range association, cancel. Fourth, we analyze a limiting case in which the long-range association can be described in terms of a Xi coalescent allowing for simultaneous multiple mergers of ancestral lines.

Genetics

bottlenecks

Linkage disequilibrium

Författare

Elke Schaper

Göteborgs universitet

Anders Eriksson

University of Cambridge

Marina Rafajlovic

Göteborgs universitet

Serik Sagitov

Göteborgs universitet

Chalmers, Matematiska vetenskaper, matematisk statistik

Bernhard Mehlig

Göteborgs universitet

Genetics

0016-6731 (ISSN)

Vol. 190 217-229

Ämneskategorier

Biologiska vetenskaper

DOI

10.1534/genetics.111.134437