Eva Jablonka

Transgenerational Epigenetic Inheritance: Prevalence, Mechanisms, and Implications for the Study of Heredity and Evolution

This review describes new developments in the study of transgenerational epigenetic inheritance, a component of epigenetics. We start by examining the basic concepts of the field and the mechanisms that underlie epigenetic inheritance. We present a comprehensive review of transgenerational cellular epigenetic inheritance among different taxa in the form of a table, and discuss the data contained therein. The analysis of these data shows that epigenetic inheritance is ubiquitous and suggests lines of research that go beyond present approaches to the subject. We conclude by exploring some of the consequences of epigenetic inheritance for the study of evolution, while also pointing to the importance of recognizing and understanding epigenetic inheritance for practical and theoretical issues in biology.

The Changing Concept of Epigenetics

Abstract: We discuss the changing use of epigenetics, a term coined by Conrad Waddington in the 1940s, and how the epigenetic approach to development differs from the genetic approach. Originally, epigenetics referred to the study of the way genes and their products bring the phenotype into being. Today, it is primarily concerned with the mechanisms through which cells become committed to a particular form or function and through which that functional or structural state is then transmitted in cell lineages. We argue that modern epigenetics is important not only because it has practical significance for medicine, agriculture, and species conservation, but also because it has implications for the way in which we should view heredity and evolution. In particular, recognizing that there are epigenetic inheritance systems through which non‐DNA variations can be transmitted in cell and organismal lineages broadens the concept of heredity and challenges the widely accepted gene‐centered neo‐Darwinian version of Darwinism.

Towards a new developmental synthesis: adaptive developmental plasticity and human disease

1focusing mainly on short-term outcomes such as infant survival and stunting. 2 However, the longer term eff ects on adult health 3 of a poor start to life suggest a further perspective. Developmental eff ects have been viewed traditionally in the context of major disruptions such as caused by teratogens, prematurity and growth retardation, but there is increasing appreciation of the role of developmental plasticity, which provides individuals with the fl exibility to adjust their trajectory of development to match their environment. Plasticity operates across the entire range of environment, from undernutrition to excessive nutritional environments associated with gestational diabetes or maternal obesity, 4,5

Epigenetic inheritance in evolution

We discuss the role of cell memory in heredity and evolution. We describe the properties of the epigenetic inheritance systems (EISs) that underlie cell memory and enable environmentally and developmentally induced cell phenotypes to be transmitted in cell lineages, and argue that transgenerational epigenetic inheritance is an important and neglected part of heredity. By looking at the part EISs have played in the evolution of multicellularity, ontogeny, chromosome organization, and the origin of some post‐mating isolating mechanisms, we show how considering the role of epigenetic inheritance can sometimes shed light on major evolutionary processes.

Information: Its Interpretation, Its Inheritance, and Its Sharing

The semantic concept of information is one of the most important, and one of the most problematical concepts in biology. I suggest a broad definition of biological information: a source becomes an informational input when an interpreting receiver can react to the form of the source (and variations in this form) in a functional manner. The definition accommodates information stemming from environmental cues as well as from evolved signals, and calls for a comparison between information‐transmission in different types of inheritance systems—the genetic, the epigenetic, the behavioral, and the cultural‐symbolic. This comparative perspective highlights the different ways in which information is acquired and transmitted, and the role that such information plays in heredity and evolution. Focusing on the special properties of the transfer of information, which are very different from those associated with the transfer of materials or energy, also helps to uncover interesting evolutionary effects and suggests better explanations for some aspects of the evolution of communication.

Evidence, mechanisms and models for the inheritance of acquired characters

Several different types of epigenetic inheritance system enable alternative functional states to be maintained in cell lineages that have identical DNA sequences. Both random and guided (directed) epigenetic variations can be transmitted by these systems, and lead to heritable modifications in cell structure and function. Although it is usually assumed that epigenetic inheritance does not occur between generations, both old and new experimental evidence suggest, and in some cases show explicitly, that epigenetic variations can be transmitted from parents to progeny. Simple models of epigenetic inheritance in asexual and sexual organisms are presented. These show that in populations of asexual unicellular organisms, the distinctive properties of induced epigenetic variations mean that the variations may be retained for many generations after the inducing stimulus is removed, even in the absence of selection. The models also show that the epigenetic systems enable some types of acquired character to be inherited in sexual, as well as asexual, organisms. The importance of epigenetic inheritance systems in the evolution of multicellularity is discussed.

Precis of Evolution in Four Dimensions

In his theory of evolution, Darwin recognized that the conditions of life play a role in the generation of hereditary variations, as well as in their selection. However, as evolutionary theory was developed further, heredity became identified with genetics, and variation was seen in terms of combinations of randomly generated gene mutations. We argue that this view is now changing, because it is clear that a notion of hereditary variation that is based solely on randomly varying genes that are unaffected by developmental conditions is an inadequate basis for evolutionary theories. Such a view not only fails to provide satisfying explanations of many evolutionary phenomena, it also makes assumptions that are not consistent with the data that are emerging from disciplines ranging from molecular biology to cultural studies. These data show that the genome is far more responsive to the environment than previously thought, and that not all transmissible variation is underlain by genetic differences. In Evolution in Four Dimensions (2005) we identify four types of inheritance (genetic, epigenetic, behavioral, and symbol-based), each of which can provide variations on which natural selection will act. Some of these variations arise in response to developmental conditions, so there are Lamarckian aspects to evolution. We argue that a better insight into evolutionary processes will result from recognizing that transmitted variations that are not based on DNA differences have played a role. This is particularly true for understanding the evolution of human behavior, where all four dimensions of heredity have been important.

‘Lamarckian’ mechanisms in darwinian evolution

Since the Modern Synthesis, evolutionary biologists have assumed that the genetic system is the sole provider of heritable variation, and that the generation of heritable variation is largely independent of environmental changes. However, adaptive mutation, epigenetic inheritance, behavioural inheritance through social learning, and language-based information transmission have properties that allow the inheritance of induced or learnt characters. The role of induced heritable variation in evolution therefore needs to be reconsidered, and the evolution of the systems that produce induced variation needs to be studied.

Epigenetic Contribution to Covariance Between Relatives

Recent research has pointed to the ubiquity and abundance of between-generation epigenetic inheritance. This research has implications for assessing disease risk and the responses to ecological stresses and also for understanding evolutionary dynamics. An important step toward a general evaluation of these implications is the identification and estimation of the amount of heritable, epigenetic variation in populations. While methods for modeling the phenotypic heritable variance contributed by culture have already been developed, there are no comparable methods for nonbehavioral epigenetic inheritance systems. By introducing a model that takes epigenetic transmissibility (the probability of transmission of ancestral phenotypes) and environmental induction into account, we provide novel expressions for covariances between relatives. We have combined a classical quantitative genetics approach with information about the number of opportunities for epigenetic reset between generations and assumptions about environmental induction to estimate the heritable epigenetic variance and epigenetic transmissibility for both asexual and sexual populations. This assists us in the identification of phenotypes and populations in which epigenetic transmission occurs and enables a preliminary quantification of their transmissibility, which could then be followed by genomewide association and QTL studies.

DNA hypomethylation causes an increase in DNase-I sensitivity and an advance in the time of replication of the entire inactive X chromosome

SummaryWe have examined the effect of 5-azacytidine (5-aza-C) induced hypomethylation of DNA on the time of replication and DNase I sensitivity of the X chromosomes of female Gerbillus gerbillus (rodent) lung fibroblast cells. Using in situ nick translation to visualise the potential state of activity of large regions of metaphase chromosomes we show that 5-aza-C causes a dramatic increase in the DNase-I sensitivity of the entire inactive X chromosome of female G. gerbillus cells and this increase in nuclease sensitivity correlates with a large shift in the time of replication of the inactive X chromosome from late S phase to early S phase. These effects of 5-aza-C on the inactive X chromosome are associated with a 15% decrease in DNA methylation. Our results indicate that DNA methylation concomitantly affects both the time of replication and the chromatin conformation of the inactive X chromosome.