Epistasis and balanced polymorphism influencing complex trait variation

Abstract

Complex traits such as human disease, growth rate, or crop yield are polygenic, or determined by the contributions from numerous genes in a quantitative manner. Although progress has been made in identifying major quantitative trait loci (QTL), experimental constraints have limited our knowledge of small-effect QTL, which may be responsible for a large proportion of trait variation. Here, we identified and dissected a one-centimorgan chromosome interval in Arabidopsis thaliana without regard to its effect on growth rate, and examined the signature of historical sequence polymorphism among Arabidopsis accessions. We found that the interval contained two growth rate QTL within 210 kilobases. Both QTL showed epistasis; that is, their phenotypic effects depended on the genetic background. This amount of complexity in such a small area suggests a highly polygenic architecture of quantitative variation, much more than previously documented. One QTL was limited to a single gene. The gene in question displayed a nucleotide signature indicative of balancing selection, and its phenotypic effects are reversed depending on genetic background. If this region typifies many complex trait loci, then non-neutral epistatic polymorphism may be an important contributor to genetic variation in complex traits.

Fragmentation of Two Quantitative Trait Loci Controlling Collagen-Induced Arthritis Reveals a New Set of Interacting Subloci

“…This means that groups of weaker loci that act in the same direction are detected as one strong locus. It is reasonable to believe that it also means that groups of loci that act in opposite directions are detected as very weak loci or not detected at all, an assumption that is supported by studies of complex traits in other model organisms, such as Drosophila and Arabidopsis, which lend themselves to investigation more easily (12,13).…”

Detection of epistatic interactions in association mapping populations: an example from tetraploid potato

“…Furthermore, epistatic interactions have also been identified in model species as well as various crops using populations of near-isogenic lines (for example, Eshed and Zamir, 1996;Kroymann and Mitchell-Olds, 2005) or linkage mapping populations (for example, Blanc et al, 2006), where differing conclusions about the importance of epistasis have been made in different studies. It has been suggested that this observation might be because of the differing experimental materials used (Eshed and Zamir, 1996).…”

Naturally segregating loci exhibit epistasis for fitness

“…Epistasis is routinely invoked to explain reproductive isolation between species via Dobzhansky-Muller incompatibilities-interactions between heterospecific alleles that cause reduced fitness in hybrids [9,10]. Multiple studies suggest that epistasis contributes to fitness differences between populations within a species [11], including direct evidence from field assays [4,12]. However, evidence for epistasis in fitness for loci that are naturally segregating within populations is limited.…”