21.1 What is Epigenetics?

The term epigenetics was first used by Conrad Waddington (Figure 21.1) in 1942 to describe how, through the process of development, a genotype produces a phenotype. In coining the term, Waddington combined the words “epigenesis,” which is how an embryo develops, with “genetics,” the study of genes and heredity. Waddington’s goal was to encourage the merging of genetics and development. However, his use of the term preceded our modern understanding of DNA and chromosome structure, and today epigenetics has taken on a narrower meaning.

Figure 21.1: Carl Waddington first used the word epigenetics to refer to how a phenotype develops from a genotype.

[Godfrey Argent Studio/The Royal Society.]

The Greek root “epi” means “over” or “above”; epigenetics has come to represent the inheritance of variation above and beyond differences in DNA sequence. Today epigenetics usually refers to the phenotypes and processes that are transmitted to other cells and sometimes future generations, but are not the result of differences in the DNA base sequence. Often epigenetic effects are caused by changes in gene expression that result from alterations to chromatin structure or other aspects of DNA structure, such as DNA methylation. One definition of an epigenetic trait is: a stably inherited phenotype resulting from changes in chromatin without alterations in the DNA sequence. Some have broadened the definition of epigenetics to refer to any alteration of chromatin or DNA structure that affects gene expression. Here, we will use epigenetics to refer to changes in gene expression and/or a phenotype that are potentially heritable without alteration of the underlying DNA base sequence.

Many epigenetic changes are stable, persisting across cell divisions or even generations. However, epigenetic alterations are also potentially influenced by environmental factors. For example, environmental stress has been shown to alter methylation of the rat Bdnf gene, which encodes a growth factor that plays an important role in brain development. DNA methylation has been tied to the expression of genes and the phenotypes they produce. As we will see, altered DNA methylation is capable of being replicated across cell division, resulting in progeny with the new phenotype, although there is no corresponding difference in the DNA base sequence of individuals that “inherit” the new phenotype. The fact that epigenetic traits may be induced by environmental effects and transmitted to future generations has been interpreted by some to mean that genes have memory through epigenetics—that environmental factors acting on individuals can have effects that are transmitted to future generations, as was seen with the effect of diet on life expectancy in the introduction to this chapter. Epigenetics has been called “inheritance, but not as we know it.”

Epigenetics is providing an explanation for how changes outside of the DNA sequence can influence the phenotype and how those changes are heritable. It is also making important contributions to the study of behavior, environmental science, cancer, neurobiology, and pharmacology. TRY PROBLEM 2