Antagonistic coevolution of two imprinted loci with pleiotropic effects.

At a locus subject to genomic imprinting, the expression pattern of an allele depends on its parent of origin. Typically, one allele is expressed while the other is transcriptionally silent, and natural selection at the locus will be driven by the inclusive fitness of the active allele. For some aspects of phenotype, the relevant fitness function differs between maternally and paternally derived alleles, so that maternally and paternally expressed imprinted loci become involved in an intragenomic, interlocus conflict. Here I consider the consequences of such a conflict between loci with pleiotropic effects and show that phenotypes are driven away from their optimal values, resulting in a maladaptive, but selectively favored, evolutionary trajectory. The extent to which the evolutionarily stable state departs from the optimal phenotype depends only linearly on the magnitude of the conflict, but is extremely sensitive to the relationship between the pleiotropic effects of the two loci. Thus, even a small intragenomic conflict can have significant deleterious consequences for multiple aspects of phenotype. This result has potential consequences for our understanding of disease states that occur at high frequency in the population, including several common psychological and behavioral disorders such as schizophrenia, bipolar disorder, major depression, and autism.