Epigenetics in comparative biology: why we should pay attention

Abstract

The past decade has seen an explosion of articles in scientific journals involving non-genetic influences on phenotype through modulation of gene function without changes in gene sequence. The excitement in modern molecular biology surrounding the impact exerted by the environment on development of the phenotype is focused largely on mechanism and has not incorporated questions asked (and answers provided) by early philosophers, biologists, and psychologists. As such, this emergence of epigenetic studies is somewhat "old wine in new bottles" and represents a reformulation of the old debate of preformationism versus epigenesis-one resolved in the 1800s. Indeed, this tendency to always look forward, with minimal concern or regard of what has gone before, has led to the present situation in which "true" epigenetic studies are believed to consist of one of two schools. The first is primarily medically based and views epigenetic mechanisms as pathways for disease (e.g., "the epigenetics of cancer"). The second is primarily from the basic sciences, particularly molecular genetics, and regards epigenetics as a potentially important mechanism for organisms exposed to variable environments across multiple generations. There is, however, a third, and separate, school based on the historical literature and debates and regards epigenetics as more of a perspective than a phenomenon. Against this backdrop, comparative integrative biologists are particularly well-suited to understand epigenetic phenomena as a way for organisms to respond rapidly with modified phenotypes (relative to natural selection) to changes in the environment. Using evolutionary principles, it is also possible to interpret "sunsetting" of modified phenotypes when environmental conditions result in a disappearance of the epigenetic modification of gene regulation. Comparative integrative biologists also recognize epigenetics as a potentially confounding source of variation in their data. Epigenetic modification of phenotype (molecular, cellular, morphological, physiological, and behavioral) can be highly variable depending upon ancestral environmental exposure and can contribute to apparent "random" noise in collected datasets. Thus, future research should go beyond the study of epigenetic mechanisms at the level of the gene and devote additional investigation of epigenetic outcomes at the level of both the individual organism and how it affects the evolution of populations. This review is the first of seven in this special issue of Integrative and Comparative Biology that addresses in detail these and other key topics in the study of epigenetics.

Fig. 1

A Venn diagram of the relationships between, and characteristics of, studies in intra-generational epigenetics common in the medical sciences, transgenerational epigenetics favored in the basic life sciences, and epigenetics as a “perspective.” The sizes of the domains are not to scale. See text for further discussion.

Fig. 2

A schematic interpretation of Waddington’s (1959) conception of what he called “the logical structure of the evolutionary system.” This figure, from his 1959 paper, illustrates how changes in gene frequency between successive generations involve interactions between what Waddington differentiated as four distinct subsystems—the exploitive, epigenetic, the natural selective, and the genetic.

Fig. 3

The relationships between, and definitions of, various forms of epigenetic inheritance.

Fig. 4

The external environment interacts with the internal environment to influence fetal development with both immediate and life-long consequences. Such environmentally-induced changes can occur at all levels of biological organization. Ultimately, these influences may be epigenetic in nature, inducing mitotically heritable alterations in gene expression without changing the DNA. Epigenetics can be studied in a reductionist manner (Molecular) to understand the manner in which gene expression is altered. Alternatively, epigenetic modifications can be examined as consequences (Molar) amplifying through higher levels of biological organization. For example, these alterations can bring about functional differences in brain and behavior that result in changes in the phenotype. Behavior is the product of brain activity and is an emergent property. Behavior becomes an externalized signal that changes the social environment; in essence the individual's behavior creates its own niche space and modifies how individuals respond to conspecifics and their environment. The evolutionary impact of such questions is still an open question. What is known is that human society has changed the ecosystem in a manner that has had demonstrable impact on the health of humans and wildlife. Figure modified from Crews (2008).

Fig. 5

Body mass changes as a function of development in neonatal water fleas, Daphnia magna. Neonates from mothers exposed to hypoxia for 6 days produced offspring that were significantly smaller in body mass for the first 6 days of their own development. See text for additional discussion. Modified from Andrewartha and Burggren (2012).