A Molecular Quantitative Genetic Study of Epistasis and Its Evolutionary Role

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9419992 CHEVERUD Many traits are affected by multiple genes. Studying the interactions among these genes, epistasis, is essential for understanding the genetic basis for these complex traits. Gene interaction, for example, may cause a disease to occur in some families but not others depending on what sets of genes are in those families. The extent of epistasis is also important for the amount of flexibility available in small populations to respond to selective pressures, to avoid extinction or as part of speciation. The amount of gene interaction on adult body weight in mice will be measured and then the effects of that interaction on inherited differences between animals in small populations will be followed. Standard population genetic theory predicts a sharp decline in inherited differences as inbreeding occurs in small populations, thus limiting their evolutionary potential. However, new models incorporating the effects of epistasis predict only a slight decline, or even an increase in the level of inherited differences, with inbreeding. Two inbred strains of mice will be crossed. Fifty small populations (4 animals) and two large populations (100 animals) will be derived from this cross. The overall average level of inherited differences between mice and the differences due to each previously identified gene will be compared between the large and small population size treatments and the results interpreted in the light of evolutionary models incorporating epistasis.