Marion J. Lamb

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.

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.

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.

Meiotic pairing constraints and the activity of sex chromosomes

The state of activity and condensation of the sex chromosomes in gametocytes is frequently different from that found in somatic cells. For example, whereas the X chromosomes of XY males are euchromatic and active in somatic cells, they are usually condensed and inactive at the onset of meiosis; in the somatic cells of female mammals, one X chromosome is heterochromatic and inactive, but both X chromosomes are euchromatic and active early in meiosis. In species in which the female is the heterogametic sex (ZZ males and ZW females), the W chromosome, which is often seen as a condensed chromatin body in somatic cells, becomes euchromatic in early oocytes. We describe an hypothesis which can explain these changes in the activity and condensation of sex chromosomes in gametocytes. It is based on the fact that normal chromosome pairing seems to be essential for the survival of sex cells; chromosomal anomalies resulting in incomplete pairing during meiosis usually result in gametogenic loss. We argue that the changes seen in the sex chromosomes reflect the need to avoid pairing failure during meiosis. Pairing normally requires structural and conformational homology of the two chromosomes, but when the regions is avoided when these regions become heterochromatinized. This hypothesis provides an explanation for the changes found in gametocytes both in species with male heterogamety and those with female heterogamety. It also suggests possible reasons for the frequent origin of large supernumerary chromosomes from sex chromosomes, and for the reported lack of dosage compensation in species with female heterogamety.

THE EVOLUTION OF HETEROMORPHIC SEX CHROMOSOMES

The facts and ideas which have been discussed lead to the following synthesis and model.

Sex Chromosomes and Speciation

Studies of reproductive isolation between animal species have shown (i) that if one sex of the hybrids between two species is sterile or inviable, it is usually the heterogametic sex (Haldane’s rule), and (ii) the genes on the sex chromosomes play a particularly large role in hybrid sterility and inviability. We propose an explanation for these two observations which is based on the changes in chromosome conformation which take place during gametogenesis. These changes are far greater in sex chromosomes than in autosomes. They are also greater in the heterogametic than in the homogametic sex. We suggest that the sensitivity of hybrids of the heterogametic sex to the genetic divergence that occurs during periods of population isolation is partly the result of the failure of their sex chromosomes to undergo appropriate conformational changes. This hypothesis explains why the sex chromosomes play a disproportionate role in post-zygotic, but not in pre-zygotic, isolation, and why often only the germ line is sensitive to hybridization.

The DNA content of polytene nuclei in midgut and Malpighian tubule cells of adultDrosophila melanogaster

SummaryThe amounts of DNA in midgut and Malpighian tubule cells of adult maleDrosophila melanogaster have been determined by Feulgen-DNA cytophotometry. The DNA values fall into discrete classes reflecting different levels of polyteny. The maximum level is 64C in the midgut, 256C in Malpighian tubules, and the modal values are 32C and 128C respectively. The data provide no evidence for extensive underreplication of heterochromatin. It is suggested that the reduced amount of satellite DNA found in the tissues of young adult flies may be a consequence of the fact that cycles of DNA replication started in the pre-adult stages are not completed until some hours after eclosion.

Heat tolerance changes with age in normal and irradiated Drosophila melanogaster

Abstract The survival times in dry air at 35°C of adult male Drosophila melanogaster which had been irradiated when 2 days old with 35 krad 60 Co γ-rays were compared with those of unirradiated control flies. With increase in age survival times decreased for both control and irradiated flies, but until middle age the irradiated flies survived longer than the controls. In saturated air the controls had greater survival times than irradiated flies of the same age. It is concluded that the relative survival times in dry air were in part a reflection of differences in the abilities of flies to withstand desiccation and that the greater survival times of irradiated flies may have been due to factors such as lower activity which reduced the rate of water loss. The results are discussed in relation to theories of radiation-induced life-shortening and it is suggested that they are not incompatible with the theories which suggest that radiation may affect the natural ageing process.

Metabolic changes in ageing Drosophila melanogaster.

Abstract As Drosophila melanogaster ages, the amount of food eaten per day increases. The amount of uric acid excreted falls, probably because there is a decline in the efficiency of synthesis. Reserves of body fat and glycogen also fall. These changes are found both for flies kept on a high fat/low carbohydrate diet and for those kept on a low fat/high carbohydrate diet. The rate of food intake is greater for old flies kept on the high fat diet. Flies transferred from this diet to the low fat diet reduce their food intake, while with the reverse transfer food intake is increased. These results suggest that old flies may have impaired energy metabolism, that they eat more to compensate for this, and that carbohydrate is a more effective energy source than fat. The shorter lifespan of flies kept on a high fat diet may be associated with an increased dependence on carbohydrate for energy metabolism.