[lbo-talk] The Epigenome in Evolution: Beyond the Modern Synthesis

Chuck Grimes cgrimes at rawbw.com
Wed May 13 20:10:14 PDT 2009


[ Extracted from

http://www.bionet.nsc.ru/vogis/pict_pdf/2008/t12_1_2vogis_12_1_2_21.pdf

Most of the citations are omitted. Modern Synthesis is the name for what we call the theory of evolution. It has]

....two major conclusions:

(1) that evolution is gradual, being explicatory in terms of small genetic changes and recombination and in terms of the ordering of this genetic variation by natural selection; and (2) that by introducing the population concept, by considering species as reproductively isolated aggregates of populations, and by analyzing the effect of ecological factors (niche occupation, competition, adaptive radiation) on diversity and on the origin of higher taxa, one can explain all evolutionary phenomena in a manner that is consistent both with the known genetic mechanisms [Mendelian genetics and the chromosomal theory] and with the observational evidence of the naturalists. Julian Huxley (1942) designated the achievement of consensus on these points as the evolutionary synthesis. It required that the naturalists abandon their belief in soft inheritance and that the experimentalists give up typological thinking and be willing to incorporate the origin of diversity in their research programs. It led to a decline in the concept of `mutation pressure' and its replacement by a heightened confidence in the powers of natural selection, combined with a new realization of the immensity of genetic variation in natural populations. ...The major, positive and negative, assumptions relating to heredity and variation in the molecular version of the Modern Synthesis can be summarized as follows (Jablonka, Lamb, 2005):

• Heredity is through the transmission of germline genes, which are discrete units located on chromosomes. Genes are DNA sequences and hereditary variation is equated with variation in DNA. There are no inherited non-DNA variations that cannot be reduced to genetic inheritance.

• Hereditary variation is the consequence of the many random allelic combinations generated by sexual processes, and each allele usually has only a small phenotypic effect. New variations in genes – mutations – are the result of accidental changes; hereditary variation is not affected by the developmental history of the individual. There is no «soft inheritance», in which heritable variations are the result of environmental effects, use and disuse, or other factors.

• Selection occurs among individuals that are, at all times, well- defined entities. Gradually, through the selection of individuals with phenotypes that make them more adapted to their environment than others are, some alleles become more numerous in the population. Mutation pressure (including genome-wide changes) is of secondary, marginal importance. • Evolution occurs through modifications from a common ancestor, and is based on vertical descent. Horizontal gene transfer (HGT) is of minor significance – it does not alter the basic tree structure of biological evolution.

• Macroevolution is continuous with microevolution, and does not require any extra selective processes or molecular mechanisms beyond those operating during microevolution. This accepted view is now beginning to be challenged in the West. Biologists are arguing that:

1. Not all heritable variation stems from DNA differences

2. Not all heritable variation is random in origin

3. Not all evolutionary change is gradual

4. Not all patterns of evolutionary divergence are tree-like. In the former USSR, the first three of these challenges were accommodated by the broader view of heredity that existed there.(Belyaev et al., 1981a, b; Belyaev, Borodin, 1982; Ruvinsky et al., 1983a, b, 1986; Trut et al., 2004; Popova, 2006). Today their studies can be interpreted within the developing framework of epigenetic inheritance, particularly the aspect that sees a role for epigenetic control in macroevolution under conditions of stress.

Epigenetics, epigenetic inheritance, and epigenetic inheritance systems

Epigenetics is concerned with those aspects of development that lead to flexibility and adjustment when the environment or the genome changes. The complementary nature of developmental stability and developmental plasticity, and their ecological and evolutionary significance, were recognized long ago, particularly by C. Waddington (1957) in Great Britain and I. Schmalhausen (1949) in the USSR. Epigenetics, a term coined by Waddington, explores the interactions between genes, their products, and the environment, and highlights the processes that decouple genetic and phenotypic variation. Epigenetic studies explore the regulatory mechanisms that can lead to long-term, persistent, developmental effects: to the establishment of variant cellular states that are transmitted across cell divisions, or that are dynamically maintained for a long periods in non-dividing cells.... Usually changes in DNA sequence are not involved, but in some cases...epigenetic control mechanisms do generate regulated alternations in DNA...

Today the term epigenetic inheritance is used in two overlapping ways...

(i) Epigenetic inheritance in the broad sense is the inheritance of developmental variations that do not stem from differences in DNA sequence or from persistent inducing signals in the environment. It includes cell heredity in unicellular and multicellular organisms and soma to soma information-transfer that is based on interactions between groups of cells, between systems, and between individuals. Soma to soma transmission by-passes the germ line, it takes place through developmental interactions between mother and embryo...

(2) Cellular epigenetic inheritance is the transmission from mother cell to daughter cell of variations that are the result of DNA differences or persistent inducing signals in the cell's environment. It occurs during cell division in prokaryotes, during mitotic cell division in soma of eukaryotes, and sometimes also during the meiotic division in the germ-line that give rise to sperm or eggs. In the latter case, offspring may inherit epigenetic variations. In both the soma and germ-line, transmission can be through chromatin marks (the non-DNA parts of chromosomes, which includes binding proteins and DNA modifications that do not affect the sequence or code), through RNAs, through self-reconstructing three-dimensional structures, and through self-sustaining metabolic loops...

The mechanisms that lead to cellular epigenetic inheritance also underlie cell memory -- the persistence of functional and structural cellular states in long-lived, non-dividing cells. For example, epigenetic mechanisms, including DNA methylation and histone modifications, are involved in stable gene-expression patterns in neurons... In rats, early maternal behaviour has long-term behavioral effects on the young, and these are associated with chromatin marks in the key gene in brain cells...

Epigenetic inheritance in conditions of stress: guiding genetic selection, generating local mutational biases, and causing systemic mutations

...Schemalhausen ... and ..Waddington... suggested that development has a guiding role in evolution. Developmental adjustments to changes experienced by organisms, especially under conditions of stress, reveal previously hidden genetic differences between individuals in their ability to adjust, and this variation can be selected. The genetic variants that contribute most to the adaptive responses therefore increase in frequency. In this way, selection can lead to change from a stimulus-dependent to stimulus independent (or less dependent) phenotype, a process that was called <<stabilizing selections>> by Schmalhausen and <<genetic assimilation>> by Waddington ...

West-Eberhard (2003) has recently developed and extended the idea that developmental plasticity plays a key role in evolution. In general framework for evolutionary thinking that she constructed, environmentally-induced changes in development are followed by genetic changes, which are selected because they simulate or stabilize the induced developmental changes, or ameliorate their adverse effects. She called this development guiding process, which includes but is not limited to genetic assimilation, <<genetic accomodation>>. Jablonka and Lamb argued that processes of genetic assimilation and accommodation would be enhanced if the induced development effects can be inherited between generations, and this possibility has been modelled by Pal. During conditions of stress, epigenetic inheritance is likely to be particularly important because of this accelerating effect.

Epigenetic inheritance and the mechanisms underlying it may have a role not only in guiding the selection of genetic variations, they may also have direct effects on the generation of genetic variants. Heritable variations in chromatin can bias changes in DNA sequence: they can affect genetic variation by influencing rates of mutation, transposition, and recombination... For example, whereas highly methlylated transposable elements in plants rarely move, when the same elements are demethylated they are usually mobile. When transposable elements move to new locations, they introduce changes in coding or regulatory sequences, and they are regarded as a major source of mutations, so their epigenetic state (e.g. the extent to which they are methlylated) affects the rate at which mutations are generated....

....What are the mechanisms underlying genomic stress response? We are only just beginning to understand how epigenetic control systems are involved in the generation of systemic mutations, but it is plausible that processes such as those seen in ciliates, where epigenetic control systems cause targeted deletions and amplifications of genes in the developing macronucleus ... may be involved in other organisms under conditions of genomic and ecological stress. It is very intriguing that the deletion or silencing ... of chromosomal regions that remain unpaired during meiosis (including the unpaired regions of X and Y chromosomes in heterogametic males) are also mediated by epigenetic control systems, probably involving small RNAs that are generated from unpaired regions... Mechanisms based on DNA-DNA, DNA-RNA, and RNA-RNA pairing interactions, coupled with chromatin or DNA enzymatic modifications, may be the genomic responses that underlie the systemic mutations that occur under conditions of stress. The genomic stress response mechanisms are evolved mechanisms, selected to deal with various hazards, including DNA damage, genomic parasites, infections, and physiological (nutritioinal, chemical, climatic) extremes...

Conclusions

Going back to the four challenges to the Modern Synthesis with which we began this paper, it should be clear from the evidence we have outlined, first that many heritable developmental variations are epigenetic rather than genetic. Second, that soft inheritance is common, since many new variants arise in response to environmental signals and are developmentally regulated. Such soft inheritance can affect the direction of evolution, revealing cryptic genetic variation and enhancing the generation of local genetic variations. Third, epigenetic control mechanisms affect genomic repatterning under conditions of stress, which can lead to macro-evolutionary changes.

We have not explored here the fourth challenge to the Modern Synthesis -- the challenge to the tree metaphor of phylogeny -- which is beyond the scope of this paper, but we would like to outline the nature of this challenge. The tree metaphor is based on the assumption that the pattern of evolution is branching, with each branch-point starting from a single common ancestor; phylogenies do not have a web-like pattern, with branches having several common ancestors. However, if cellular stresses arising from genetic exchanges through hybridization, horizontal gene transfer, or other forms of genetic exchange are common in evolution, this assumption has to be re-evaluated. In early evolution, horizontal gene transfer may have been the rule rather than the exception, and it may still be a major importance today, especially for evolution of microorganisms. The actual pattern of evolution is probably partly tree and partly web, with tree or web patterns dominating at different times and for different taxa.

We are living through a period of revolutionary change in the biological sciences, and we believe that a post-Synthesis era is beginning in evolutionary biology...



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