The penetrance of an epigenetic trait in mice is progressively yet reversibly increased by selection and environment

Abstract

Natural selection acts on variation that is typically assumed to be genetic in origin. But epigenetic mechanisms, which are interposed between the genome and its environment, can create diversity independently of genetic variation. Epigenetic states can respond to environmental cues, and can be heritable, thus providing a means by which environmentally responsive phenotypes might be selectable independent of genotype. Here, we have tested the possibility that environment and selection can act together to increase the penetrance of an epigenetically determined phenotype. We used isogenic A vy mice, in which the epigenetic state of the A vy allele is sensitive to dietary methyl donors. By combining methyl donor supplementation with selection for a silent A vy allele, we progressively increased the prevalence of the associated phenotype in the population over five generations. After withdrawal of the dietary supplement, the shift persisted for one generation but was lost in subsequent generations. Our data provide the first demonstration that selection for a purely epigenetic trait can result in cumulative germline effects in mammals. These results present an alternative to the paradigm that natural selection acts only on genetic variation, and suggest that epigenetic changes could underlie rapid adaptation of species in response to natural environmental fluctuations.

Transgenerational epigenetic effects on animal behaviour

“…Our group found that a modified foraging behaviour in chickens, in response to an undpredictable day length, was mirrored in the female offspring; also the associated change in brain gene expression profile was similar in the offspring (Nätt et al, 2009). And, as shown by the earlier discussed experiment by Cropley and co-workers, selection for epigenetic variation can cause an increase in epialleles over several generations, much in accordance with what we know from selection on genetic mutations (Cropley et al, 2012).…”

“…A beautiful demonstration that evolution can act on epigenetic variation even in the absence of genetic differences is provided by the experiment by Cropley and co-authors (Cropley, Dang, Martin, & Suter, 2012). They studied the inheritance of the pseudo-agouti phenotype in mice, which is caused by a methylated epi-allele.…”

“…It is also clear that selection can act on epigenetic variation, effectively creating an evolutionary pathway which is independent of genetic mutations (Cropley et al, 2012).…”

Epigenetic Inheritance: A Contributor to Species Differentiation?

“…The instability of many inherited epigenetic states has led to the view that it can be a mechanism of phenotypic response to environmental factors, one that can readily be reversed when such factors change ( Jirtle and Skinner, 2007;Petronis, 2010;Richards, 2011;Skinner, 2011;Cropley et al, 2012). But, is it more than that?…”

Epigenetic Inheritance of Disease and Disease Risk

“…Because of conflicting results, however, the idea that such a diet-induced shift can be inherited across several generations is still controversial. When pseudoagouti females were chosen for breeding and were fed a diet supplemented with methyl donor, a transgenerational phenotypic shift toward the 'silent', methylated phenotype could indeed be demonstrated across two generations (Cropley et al, 2006;Cropley et al, 2012). If, however, mice carrying the weakly methylated allele (yellow or motteled phenotype) were chosen for breeding, no transgenerational shift in phenotype was observed (Cropley et al, 2007;Waterland et al, 2007a).…”