  Biochemical and regulatory interactions central to biological networks are
expected to cause extensive genetic interactions or epistasis affecting the
heritability of complex traits and the distribution of genotypes in
populations. However, the inference of epistasis from the observed
phenotype-genotype correlation is impeded by statistical difficulties, while
the theoretical understanding of the effects of epistasis remains limited, in
turn limiting our ability to interpret data. Of particular interest is the
biologically relevant situation of numerous interacting genetic loci with small
individual contributions to fitness. Here, we present a computational model of
selection dynamics involving many epistatic loci in a recombining population.
We demonstrate that a large number of polymorphic interacting loci can, despite
frequent recombination, exhibit cooperative behavior that locks alleles into
favorable genotypes leading to a population consisting of a set of competing
clones. When the recombination rate exceeds a certain critical value that
depends on the strength of epistasis, this "genotype selection" regime
disappears in an abrupt transition, giving way to "allele selection"-the regime
where different loci are only weakly correlated as expected in sexually
reproducing populations. We show that large populations attain highest fitness
at a recombination rate just below critical. Clustering of interacting sets of
genes on a chromosome leads to the emergence of an intermediate regime, where
blocks of cooperating alleles lock into genetic modules. These haplotype blocks
disappear in a second transition to pure allele selection. Our results
demonstrate that the collective effect of many weak epistatic interactions can
have dramatic effects on the population structure.
