Question

How do Agouti mice show transgenerational epigenetic inheritance and how does this provide evidence for evolution. Emphasise on how this effects Darwinian selection.

Answer 1

The definition of transgenerational epigenetic inheritance is ‘germline-mediated inheritance of epigenetic information between generations in the absence of continued direct environmental influences that leads to phenotypic variation

Transgenerational Epigenetic Inheritance in the agouti mouse

Examples of transgenerational epigenetic inheritance within endogenous genes, other than imprinted genes, is relatively rare. However, one excellent example is that of the agouti viable yellow (Avy) gene. The Avy locus is actually a retrotransposon (i.e., jumping gene) that is inserted upstream of the agouti gene. Although Avy is unique to the mouse genome, the element is present in thousands of copies. Normally, these Avy elements are methylated, thus, shut off. However, in the Agouti mouse, they are unmethylated and active, leading to a yellow coat and very pronounced obesity.

The viable yellow agouti (Avy) mouse model, in which coat color variation is correlated to epigenetic marks established early in development. These two mice are genetically identical. However, they have a different epigenetic methylation pattern at a specific gene loci that impacts hair color and weight.

Mice whose agouti gene is “on” are also more likely to suffer from diabetes and cancer as adults. Additionally, these epigenetic modifications to the Axy elements can be transgenerationally inherited by the offspring. This suggests that there is a failure to clear the epigenetic marks that are established at the Axy locus in the germline. Thus, there is a clear transgenerational epigenetic inheritance via the gamete.

Female / Male Environmental Exposure Gestating Female Environmental Exposure F2- Carmine Bedie Multigenerational Exposures 1 am F2 Generation First Unexposed Transgenerational Inheritance F3 Generation First Unexposed

Evidence of Evolution

It is probably unlikely that transgenerational epigenetic inheritance is a widespread phenomenon. Certainly epigenetics plays a major role in differentiating cell types within a given organism and “adapting” these tissues to environmental exposure. Further, there is significant evidence that these changes can occur in the gametes. But I believe that the most likely outcome from these epigenetic changes is decreased fertility (i.e., decreased embryonic viability) if they aren’t completely erased during reprogramming, rather than acquired traits that are then inherited across generations. That being said, a very different way of looking at epigenetics could be as a mechanism for “long-term adaptation” or “short-term evolution”. In this case, transgenerational epigenetic inheritance becomes essentially necessary for the survival of the species.