Epigenetics and our inheritance to future generations

The concept of epigenetic inheritance is fairly recent, having emerged in the late twentieth century. Yet, epigenetic inheritance is gaining more and more attention and interest in the scientific community. Research on epigenetic inheritance continues to be published in the world’s foremost scientific journals, such as a study recently published in the journal Nature Communications. What is epigenetic inheritance, and what makes it so interesting to the scientific community?

A closer look at the history of the concepts of inheritance and evolution can inform the answers to these questions.

Ideas on evolution date from the writings of philosopher Anaximander of Miletus (c. 610-546 B.C.E.). He thought, since infants and young children require protection during early development, humans were therefore more evolutionarily recent organisms and had descended from fish and other marine life forms, whose young did not need protection.

It wasn’t until the eighteenth century that a more objective and scientifically testable hypothesis was proposed by several naturalists—that life evolves as the environment changes.

French biologist Jean-Baptiste de Lamarck (1744-1829) first proposed how life evolves. Lamarck posed three salient principles: that the more a part of the body is used, the larger and stronger it becomes and the less likely it is to deteriorate; these changes and characteristics acquired by an organism during its lifetime could be passed to offspring; and what is also known as the orthogenesis hypothesis—that organisms have an innate drive to become more complex. Lamarckism is now most famously known as an “incorrect” theory of evolution. Body parts of an organism certainly may change based on use and disuse, but bodily changes that an organism acquires (through use or disuse) during its lifetime cannot be inherited by offspring. The children of bodybuilders are not born with toned muscles. Additionally, we know that evolution is not necessarily directed towards complexity (this is among other reasons for why the orthogenesis hypothesis is now considered obsolete); the Texas blind salamander species evolved as its ancestors lost their eyes through generations of evolution.

In the mid-nineteenth century, naturalists Charles Darwin (1809-1882) and Alfred Russel Wallace (1823-1913) independently developed the theory of evolution by natural selection—the process by which evolution occurs as organisms having more survival and reproductive success pass down their heritable traits to offspring. Influenced by Lamarck’s work, Darwin also, incorrectly, believed in the heritability of acquired characteristics but rejected the orthogenesis hypothesis. As Wallace himself acknowledged, Darwin’s extensive development of the theory of natural selection still is one of the greatest contributions to biology, earning Darwin the title as the “father of evolution.” Building upon Darwin’s work, Gregor Mendel (1822-1884) conducted experiments with garden peas and flowers to study inheritance. Mendel discovered that organisms pass down discrete heritable units—what we now know as “genes“—to offspring.

The importance of this pioneering work cannot be overstated. Though the work of specifically Darwin and Wallace has most profoundly influenced our understanding of evolution, Lamarck’s impact is also lasting. For example, our current understanding of long-term memory—of how our brain encodes memories at the molecular and cellular levels—has connections to Lamarck’s hypothesis on how use and disuse result in changes at the level of individual organisms.

An interesting question then arises: Could memories be encoded at the genetic level? If so, could these memories, in the form of genetic information, be passed down to future generations?

An experience could be “genetically remembered” in the form of genetic information if it induces changes in either the genome (an organism’s entire set of DNA, the molecule that makes up genes and carries genetic information) or the epigenome (the set of chemical modifications and markers to the genome). There is evidence that, not only the genome, but also specific markers of the epigenome are heritable, provided that the epigenetic markers pass two epigenome reprogramming checkpoints. If encoded and “remembered” through the genome or epigenome, the genetic memory of an experience could potentially be inherited by future generations.

The inheritance of genetic memories could follow three patterns. In parental/intergenerational inheritance, an event experienced through a parent is encoded as a genetic memory in offspring—for example, prenatal maternal stress might be encoded as a genetic memory by offspring who may also experience the stress in utero. In multigenerational inheritance, the genetic memory is passed no further than to the immediate offspring of the individual who experienced and encoded the memory—following the previous example, the genetic memory could be passed down no further than the offspring of the individuals who experienced and encoded stress in utero (i.e., this offspring would also be the grandchildren of the prenatally stressed mother). In transgenerational inheritance, the genetic memory is passed down through individuals who have not directly experienced the memory—through the grandchildren of the prenatally stressed mother, to the great-grandchildren.

Of course, genes and DNA can be inherited parentally/intergenerationally, multigenerationally, or transgenerationally. Additionally, it has been known that some species of plants, yeasts, and roundworms show inheritance of the epigenome. But evidence for epigenetic inheritance in mammals has not emerged until within the twenty-first century. For example, in 2014, a study found intergenerational epigenetic influences in the metabolism of adult mice who were undernourished in utero via their mothers. Other studies have shown transgenerational epigenetic inheritance in mice and rats.

Researchers have shown multigenerational epigenetic inheritance in humans, studying the multigenerational inheritance of effects of psychosocial stress and lead exposure during pregnancy. To date, there is no evidence for transgenerational epigenetic inheritance in humans.

In retrospect, it can be ascertained that the Lamarckian hypothesis on the inheritance of acquired characteristics is indeed true to an extent: an experience could be encoded by an organism as a genetic memory, either in the genome or epigenome; and then potentially inherited by future generations. The genetic memory might be a remnant of the experience that changed the genome or epigenome; or, the memory could be an adaptive response to the experience at the level of the genome or epigenome. We might carry (and in turn pass down to future generations) more heritable information than we think—indeed, information also newly acquired and genetically encoded during an ancestor’s lifetime.

Research on epigenetic inheritance is not without ethical implications. For instance, scientists think that editing the epigenome might be more efficient than editing the genome; the ethics of epigenetic editing deserves careful evaluation and thoughtful discussion, considering that we know the epigenome is indeed heritable to an extent.

Inheritance is a new and exciting frontier in epigenetics research. Further research on epigenetic inheritance could inform our understanding of the relationship between inheritance and evolution, helping us understand the full extent of our inheritance to future generations.

Vishruth Nagam is an undergraduate student.

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