  We analyse interactions of Quantitative Trait Loci (QTL) in heat selected
yeast by comparing them to an unselected pool of random individuals. Here we
re-examine data on individual F12 progeny selected for heat tolerance, which
have been genotyped at 25 locations identified by sequencing a selected pool
[Parts, L., Cubillos, F. A., Warringer, J., Jain, K., Salinas, F., Bumpstead,
S. J., Molin, M., Zia, A., Simpson, J. T., Quail, M. A., Moses, A., Louis, E.
J., Durbin, R., and Liti, G. (2011). Genome research, 21(7), 1131-1138]. 960
individuals were genotyped at these locations and multi-locus genotype
frequencies were compared to 172 sequenced individuals from the original
unselected pool (a control group). Various non-random associations were found
across the genome, both within chromosomes and between chromosomes. Some of the
non-random associations are likely due to retention of linkage disequilibrium
in the F12 population, however many, including the inter-chromosomal
interactions, must be due to genetic interactions in heat tolerance. One region
of particular interest involves 3 linked loci on chromosome IV where the
central variant responsible for heat tolerance is antagonistic, coming from the
heat sensitive parent and the flanking ones are from the more heat tolerant
parent. The 3-locus haplotypes in the selected individuals represent a highly
biased sample of the population haplotypes with rare double recombinants in
high frequency. These were missed in the original analysis and would never be
seen without the multigenerational approach. We show that a statistical
analysis of entropy and information gain in genotypes of a selected population
can reveal further interactions than previously seen. Importantly this must be
done in comparison to the unselected population's genotypes to account for
inherent biases in the original population.
