Environmental factors, epigenetic changes, and genetic mutations form a chain that spans generations, contributing to disease and evolution. And a key link in this chain is genomic instability. According to a new study, genomic instability that connects back to exposure-specific epigenetic change may, through germline inheritance, lead to genetic mutations—specifically, copy number variations—that become apparent only after several generations have passed.
The new study, from Washington State University (WSU) researchers, proposes that environmental factors are having an underappreciated effect on the course of disease and evolution. It appeared August 3 in the journal Epigenetics, in an article entitled, “Environmentally induced epigenetic transgenerational inheritance of sperm epimutations promote genetic mutations.”
The WSU researchers were led by Michael K. Skinner, Ph.D., founding director of the Center for Reproductive Biology in WSU's School of Biological Sciences. In earlier work, Dr. Skinner found epigenetic effects from a host of environmental toxicants, connecting plastics, pesticides, fungicide, dioxin, and hydrocarbons to diseases and abnormalities as many as three generations later. In the current study, Dr. Skinner’s group exposed gestating female rats to the fungicide vinclozolin.
Sperm in the first generation of male offspring showed epimutations, or alterations in the methyl groups that stick to DNA and affect its activation. Third generation, or great-grand offspring, had increased genetic mutations, which the researchers saw in increased DNA structure changes known as copy-number variations. Multiple generations of control animals had no such variations.
“The genome-wide locations of differential DNA methylation regions (epimutations) and genetic mutations (CNV) were investigated,” wrote the authors. “Observations suggest the environmental induction of the epigenetic transgenerational inheritance of sperm epimutations promote genome instability, such that genetic CNV mutations are acquired in later generations.”
This, said Dr. Skinner, suggests that environment has a more important role in mutations, disease and evolution than previously appreciated, and appears to be one of the main drivers of intergenerational changes, not simply a passive component. In short, Skinner and his colleagues say, the environment and epigenetics can drive genetics.
“There's not a type of genetic mutation known that's not potentially influenced by environmental epigenetic effects,” emphasized Dr. Skinner.
In their concluding remarks, the authors noted that environmental epigenetics may be the major molecular mechanism involved in environment-gene interactions and emergence of genetic variation.
“The predominant current view for the origin and evolution of disease considers genetic mutations as the primary molecular mechanism involved,” they wrote. “Environmental impacts on the epigenome that have the ability to promote genetic mutations extend these previous views and help clarify how the environment may have direct impact on disease etiology and on the origins of phenotypic and genotypic variation in evolutionary processes.”