More than Fifty Shades of Epigenetics for the Study of Early in Life Effects in Medicine, Ecology, and Evolution

Abstract

After being coined by Conrad Waddington in the context of development, today the term epigenetics focuses on the molecular machinery beyond genes. Epigenetics is central to early in life effects and their consequences in eco-evolutionary dynamics. I review the two historical understandings of epigenetics, i.e. its Developmental and Evolutionary understandings, both concerning the molecular mechanisms occurring within an organisms’ lifetime. Although I unify them under a generic definition, these understandings are not suitable for studies at the intergenerational level. To fill this gap, I propose an inclusive understanding of epigenetics incorporating all the processes of parent–offspring resemblance that are not engraved into the DNA sequence. By integrating all mechanisms of phenotypic variation beyond the DNA sequence, this new understanding fully corresponds to the etymological meaning of the term “above, or beyond the gene.” By integrating knowledge at all levels, this broader understanding of epigenetics should help transferring all the knowledge at the infra-individual level into the study of processes unfolding at the supra-individual level to build a continuum from molecules to ecology and evolution. Concepts of inheritance and early in life effects should play a major role in building such a continuum. Classifying more than 50 definitions of epigenetics in four groups using the actual terms of the definitions reveals interesting discrepancies between definitions and ultimate scientific goals. Finally, I present some examples of how a clear vision of the various understandings of epigenetics may influence biology and argue that epigenetics now needs to percolate in ecology and evolution.

Glossary

Extended Evolutionary Synthesis

A trend in evolutionary science, that took momentum at the turn of the twenty-first century and that puts more emphasis on the role of development, environmental factors, as well as some non-genetic forms of inheritance in the evolutionary processes (mainly if not exclusively epigenetics in its developmental and evolutionary understandings: Pennisi 2008; Pigliucci and Müller 2010; Laland et al. 2015; Lu and Bourrat 2017).

Genetic

Here, I use this term in its most common modern sense of sequencic, i.e. information encoded in the DNA sequence of nucleotides. Note that this meaning is highly reductionist relative to the initial meaning that encompassed everything that participates to heredity.

Genetic assimilation

A process by which a phenotype initially induced by a specific environmental factor, becomes genetically determined through selection. Note that, at the time of Waddington, the term genetic meant anything that is inherited. In particular, Waddington’s experiments did not show that the initially plastic trait became encoded into the DNA sequence, but rather, that it lost its plasticity and became inclusively heritable (Danchin et al. 2019b).

Heredity

Patterns of parent–offspring resemblance. It is widely accepted in biology that heredity results from parents transmitting information to their offspring, though the nature of this information is still at the heart of a hot debate (e.g., Sarkar 1996; Godfrey-Smith 2000; Maynard Smith 2000; Pocheville 2018; Danchin et al. 2019b).

Heritability

Usually, this term quantifies the part of phenotypic variation that is inherited genetically, either additively (narrow sense heritability) or total (broad sense heritability). It is measured at the level of a population. It quantifies parent–offspring resemblance at play in quantitative genetics. Today heritability is usually associated to variation in DNA nucleotidic sequence alone (Danchin and Wagner 2010; Danchin et al. 2011). For more details, see (Bourrat 2015). In Table 1.1, I also point at the transposition of this term to depict the persistence of cell characteristics along cell lineages of multicellular organisms.

Inclusive Evolutionary Synthesis

The evolutionary synthesis ambitioning to incorporate all known dimensions of inheritance into a single theoretical framework. It incorporates the inclusive understanding of epigenetics that I develop here.

Inclusive heritability

Statistical term quantifying the degree of parent–offspring resemblance, whatever the mechanisms responsible for it (whether sequencic or not, Danchin and Wagner 2010; Danchin et al. 2011). It is the heredity of difference, whatever the underlying mechanism. Often in this book chapter, I use the term heritability in the meaning of inclusive heritability, because historically it was the initial meaning of this term. Inclusive heritability is the corner stone of evolution through natural selection and drift.

Infra-individual processes

Biological processes occurring within an organism during its lifetime, including gene expression, cell functioning, physiology, neurobiology, as opposed to supra-individual processes. Corresponds to what Mayr (1961) called functional biology.

Inheritance

The set of mechanisms producing parent–offspring resemblance.

Intergenerational epigenetic inheritance

The set of epigenetic mechanisms that produce resemblance between two successive generations.

Modern Synthesis (of evolution)

A trend in evolution, first coined by Julian Huxley in 1942, that brought together Darwinism, Mendelism, and population genetics in order to provide a powerful account of the mechanisms of evolution. Also called Neo-Darwinism although these two terms often cover different approaches. In this trend, the focus is mainly on genes (today understood as sequencic). A purpose of the extended or inclusive syntheses is to extend it beyond the gene.

Non-genetic inheritance

Mechanisms of inclusively heritable variation that do not result from variation in the DNA sequence (Danchin and Wagner 2010; Danchin et al. 2011). Equivalent to non-sequencic inheritance.

Sequencic

Term that was first casually used by Hervé Philippe in a discussion to depict the pervasive trend among biologists and the grand public to reduce inherited information to the sole information encoded into the DNA sequence of nucleotides. It can replace the term genocentrism that I used before that is ambiguous because of the many understandings of all the terms of the “gene” family (genetics, genomics…).

Supra-individual processes

Interactions occurring among individuals within populations, communities, and ecosystems. These integrate transgenerational processes such as heredity. This is the domain of ecology and evolution. Corresponds to what Mayr (1961) called evolutionary biology.

Transgenerational epigenetic inheritance

The set of epigenetic mechanisms that produces resemblance across multiple (≥2) generations of organisms.