Genomic imprinting of IGF2 in marsupials is methylation dependent

Research articl

An investigation of the transcriptional regulatory elements of IGF2 in the livebearing fish Poeciliopsis prolifica and the marsupial Monodelphis domestica

The Parent-Offspring Conflict Theory suggests that genomic conflict between maternal and paternal genes is the precipitating factor for imprinting, and implies that organisms possessing a placental structure that allows for the allocation of maternal resources to developing offspring will exhibit imprinting (Haig, 2000). The work conducted in this body of research examined the expression of IGF2 in the matrotrophic livebearing fish Poeciliopsis prolifica, which evolved viviparity independently of mammals, and not only found the gene to be biallelically expressed, but revealed it to be rapidly evolving in some matrotrophic lineages. In addition, the finding that residues near proteolytic sites are undergoing positive selection suggests that these placental fish may be attempting to adapt as a result of genomic conflict. In marsupials, it is already known that imprinting exists, but the mechanism by which it occurs is still unknown. It was demonstrated here that differential methylation between the parental alleles is not a factor in the regulation of expression of IGF2, but elements linked to the function of matrix attachment regions, such as deacetylation, may hold promise as transcriptional regulators. The outcome of this aspect of the study provides support for the premise that marsupials may have retained regulation of imprinting by means of acetylation while eutherians increased control with differential methylation (Wakefield et al., 1997).

Ancient and continuing Darwinian selection on insulin-like growth factor II in placental fishes

Despite abundant examples of both adaptation at the level of phenotype and Darwinian selection at the level of genes, correlations between these two processes are notoriously difficult to identify. Positive Darwinian selection on genes is most easily discerned in cases of genetic conflict, when antagonistic evolutionary processes such as a Red Queen race drive the rate of nonsynonymous substitution above the neutral mutation rate. Genomic imprinting in mammals is thought to be the product of antagonistic evolution coincident with evolution of the placenta, but imprinted loci lack evidence of positive selection likely because of the ancient origin of viviparity in mammals. To determine whether genetic conflict is a general feature of adaptation to placental reproduction, we performed comparative evolutionary analyses of the insulin-like growth factor II (IGF2) gene in teleost fishes. Our analysis included several members of the order Cyprinodontiformes, in which livebearing and placentation have evolved several times independently. We found that IGF2 is subject to positive Darwinian selection coincident with the evolution of placentation in fishes, with particularly strong selection among lineages that have evolved placentation recently. Positive selection is also detected along ancient lineages of placental livebearing fishes, suggesting that selection on IGF2 function is ongoing in placental species. Our observations provide a rare example of natural selection acting in synchrony at the phenotypic and molecular level. These results also constitute the first direct evidence of parent–offspring conflict driving gene evolution