Are we more than the sum of our genes? Three intriguing investigations add insight into the ways environment and experience shape genetic expression — sometimes in ways that can be inherited across multiple generations.
One of the set-pieces of the grade-school explanation of evolutionary theory is the triumph of Charles Darwin’s theory of natural selection over that of the French naturalist Jean-Baptiste Lamarck. In Lamarck’s world, giraffes owed their long necks to generation after generation of their forbears stretching to reach the good leaves. In Darwin’s, giraffes had longer necks because for generations, giraffes born with a predisposition for long necks had been more likely to survive and reproduce, passing along that trait to their children.
For the past century and a half, Darwin’s view has grown and been refined in light of the discovery of DNA into a neo-Darwinian consensus understanding of how individuals inherit traits and how populations and species evolve. But recent research into the so-called epigenome — chemical and markers that exist outside of the DNA code but can affect its expression — provides clues that not all inheritance comes through the genes.
MAKING ROOM FOR CHANGE
In 2013, Yoav Soen of the Weizmann Institute of Science in Israel received a multi-year grant from the John Templeton Foundation to study the ways that organisms and their offspring cope with environmental stressors. Building on preliminary studies that showed that exposing fruit fly larvae to a toxin altered not only the expected development pattern of the exposed fruit flies but also that of their descendants, Soen’s team investigated the potential mechanisms by which the alteration — which was not directly encoded in the fruit fly’s genes — could be passed on. They found two likely mechanisms by which the trait was apparently inherited. One involved the fruit flies’ microbiome: exposure to the toxin had killed off certain types of microorganisms that lived in and on the fruit flies. The alteration to the microbiome triggered some developmental delays, and was passed on when the microbiome transferred to the flies’ offspring.
The other mechanism involved effects of the toxin exposure on the fruit flies’ epigenome, in this case to their RNA, which in turn affected which of the fruit flies’ genes were switched on as the offspring developed.
Soen believes that these sort of heritable changes existing outside the genome allow for greater individual adaptation to circumstance within the broader framework of genetic inheritance and evolution through natural selection. “No doubt, natural selection is essential and powerful,” he says, “but it cannot account for all that biologists have been seeing in experiments.”
SILENT SPRING REDUX
A larger Templeton-funded grant looked at the multi-generational effects of toxin exposure on mammals. Washington State University’s Michael Skinner is a leading — and at times controversial — investigator of the role of the epigenome in diseases. His main focus has been investigating the ways that exposure to the pesticide DDT increased obesity rates in the exposed population’s descendants. The mechanisms involved include RNA (as with Soen’s fruit flies) as well as DNA methylation and histone modifications.
Skinner’s grant traces the ways that altered epigenetic information in DDT-exposed rats is transferred through the male line. Because sperm cells, unlike egg cells, are produced throughout adulthood, the epigenetic information they carry can be altered by environmental factors such chemical exposure.
The results of Skinner’s experiments replicated his earlier findings associating DDT exposure with an approximately 50 percent increase in obesity across three successive generations of unexposed offspring. Skinner also found increased rates of diseases of the testes, ovaries, kidneys and prostate.
Skinner’s research is especially compelling for the questions it raises about the lasting effects of exposure to toxins in our environment — could current rises in North American obesity have been triggered in part by widespread spraying of DDT as an insecticide in the mid-20th century?
DESTRUCTIVE PATTERNS
A third Templeton grant, recently awarded following a successful pilot study, focuses on the direct effects of chemical exposure on epigenomes of both rats and humans. Susan Murphy of the Duke University Medical Center is investigating how exposure to THC, the major active component of cannabis, alters DNA methylation in sperm cells produced, as it were, under the influence. Methylation refers to a pattern of methyl groups that attaches to an organism’s DNA. These groups are influential in switching genes on or off. Although most methylation is reset during embryonic development and thus would not be passed between generations, a portion of it is inherited.
Murphy’s initial results found that rats exposed to THC showed up to 50 percent differences in methylation compared to a control group. A parallel study examined sperm from a mix of human cannabis users and non-users, and found up to a 30 percent difference in methylation among the users.
ADAPTING WITH THE FUTURE IN MIND
The discovery that environmental exposure can result in non-genetic change that is nonetheless inheritable is seen by some as a quasi-Lamarckian challenge to the neo-Darwinist consensus. The threat of a major upheaval seems minor: an obese rat with a DDT-exposed grandfather is not quite the same as a giraffe inheriting a long neck because its forebears did extra stretches. The evidence for the myriad ways that adaptation is driven by genetic change winnowed by natural selection is substantial, compelling and has propelled enormous scientific insight.
And yet the new frontiers of the epigenome hold important new information, not just as a way of understanding how biology works but as a means of minimizing future suffering. Our genes are what they are and we have very little choice in how they get passed on. But through the epigenome, some of the many toxins we are exposed to today — whether unintentionally or voluntarily — might have effects on our grandchildren’s grandchildren. Knowing that might change our behavior today, and save our offspring no small amount of trouble.
