Epigenetics: Gene and epigene networks in ontogeny and phylogeny

An attempt was made to systematize theoretical and experimental epigenetic data in the framework of genetics as a science on laws of preservation, coding, transfer, and transformation of heritable information in the living systems. The structure of the total hereditary memory is discussed in context of the theory of epigenes, hereditary units of the next to genes level of complexity. In epigenes as cells of functional hereditary memory, part of the hereditary information is stored, coded, and transmitted to the progeny irrespective of the primary structure of the genomic DNA molecules. The principles of the structure and the general laws of functioning of cellular governing gene networks are presented. The ontogenetic and phylogenetic role of epigene networks as the second level of the hereditary system is considered. Arguments for inheritance of somatic epimutations are presented, as well as the results of in silico and in vivo experiments showing the possibility of an epigenetic mechanism of primary biochemical divergent determination (autodetermination). A network hypothesis on material carriers of the common heterotary memory is formulated.     

Epigenetics: gene and epigene networks in ontogeny and phylogeny

An attempt was made to systematize theoretical and experimental epigenetic data in the framework of genetics as a science on laws of preservation, coding, transfer, and transformation of heritable information in the living systems. The structure of the total hereditary memory is discussed in context of the theory of epigenes, hereditary units of the next to genes level of complexity. In epigenes as cells of functional hereditary memory, part of the hereditary information is stored, coded, and transmitted to the progeny irrespective of the primary structure of the genomic DNA molecules. The principles of the structure and the general laws of functioning of cellular governing gene networks are presented. The ontogenetic and phylogenetic role of epigene networks as the second level of the hereditary system is considered. Arguments for inheritance of somatic epimutations are presented, as well as the results of in silico and in vivo experiments showing the possibility of an epigenetic mechanism of primary biochemical divergent determination (autodetermination). A network hypothesis on material carriers of the common heterotary memory is formulated.     

Epigenetic heredity 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.     

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.     

表遗传学推动新一轮遗传学的发展

科学的发展孕育着突破,表遗传学研究推动着新一轮的遗传学的发展。表遗传学是研究没有DNA序列变化的、可遗传的表达改变。表遗传学不仅对医学和农业有重要的实践意义,而且还提供了理解遗传和进化的新观点。研究表明,人类基因组含有两类遗传信息,遗传学信息提供了合成生命所必需蛋白质的模板,而表遗传学信息提供了何时、何地和怎样地应用遗传学信息的指令;遗传学和表遗传学的关系有如“阴阳”,它们既相区别又协同参与调节生命活动。同时还讨论了基因的概念、进化和epigenetics的中文译名等问题。表遗传学研究应引起国内学术界的关注。Abstract: Scientific development is pregnant with a breakthrough, epigenetic studies are pushing the genetics forward. Epigenetics is the study of heritable changes in gene expression that occurs without a change in DNA sequence. Epigenetics not only has practical significance for medicine and agriculture, but also provides new views on understanding heredity and evolution. Human genome contains information in two forms: the genetic information provides the blueprint for the manufacture of all the proteins necessary to create a living thing while the epigenetic information provides instructions on how, where, and when the genetic information should be used. The interrelationship of genetics and epigenetics is like a yin-yan, they are different from each other, and cooperatively take part in regulation of a variety of living activities. In this paper concept of gene and problems of evolution has been also discussed according to epigenetic viewpoints.     

The evolution of information storage and heredity

Many important transitions in evolution are associated with novel ways of storing and transmitting information. The storage of information in DNA sequence, and its transmission through DNA replication, is a fundamental hereditary system in all extant organisms, but it is not the only way of storing and transmitting information, and has itself replaced, and evolved from, other systems. A system that transmits information can have limited heredity or indefinite heredity. With limited heredity, the number of different possible types is commensurate with, or below, that of the individuals. With indefinite heredity, the number of possible types greatly exceeds the number of individuals in any realistic system. Recent findings suggest that the emergence and subsequent evolution of very different hereditary systems, from autocatalytic chemical cycles to natural language, accompanied the major evolutionary transitions in the history of life.     

“GREENCE” technology for in silico analysis of gene network dynamics in individual cells of a clonal population

The technology developed for in silico analysis of gene network behavior in a series of successive cell divisions makes it possible to obtain gene expression profiles in the cells of intermediate and final generations and to evaluate the relation among the cells heterogeneous by the functional states of gene subnetworks. Based on the model of a hypothetical gene network, which includes three cyclic digene systems with negative feedbacks, a new property of dynamic epigenes is confirmed, i.e., metastability of some epigenotypes, which earlier was predicted theoretically and found in experiments in vivo. A dynamic epigene is a cyclic system of genes with more than one inherited functional states, or epigenotypes. In a metastable state such a relation among repressors is set in a cell that, as a result of random distribution of the molecules and fluctuations of protein concentrations, subsequent divisions give daughter cells appear determined to alternative epigenotypes. It is shown in computer experiments that even systems in which dynamic epigenes are typical elements can possess this property.

     

“GREENCE” technology for <Emphasis Type="Italic">in silico</Emphasis> analysis of gene network dynamics in individual cells of a clonal population

The technology developed for in silico analysis of gene network behavior in a series of successive cell divisions makes it possible to obtain gene expression profiles in the cells of intermediate and final generations and to evaluate the relation among the cells heterogeneous by the functional states of gene subnetworks. Based on the model of a hypothetical gene network, which includes three cyclic digene systems with negative feedbacks, a new property of dynamic epigenes is confirmed, i.e., metastability of some epigenotypes, which earlier was predicted theoretically and found in experiments in vivo. A dynamic epigene is a cyclic system of genes with more than one inherited functional states, or epigenotypes. In a metastable state such a relation among repressors is set in a cell that, as a result of random distribution of the molecules and fluctuations of protein concentrations, subsequent divisions give daughter cells appear determined to alternative epigenotypes. It is shown in computer experiments that even systems in which dynamic epigenes are typical elements can possess this property.     

Evolution of genome architecture

Charles Darwin believed that all traits of organisms have been honed to near perfection by natural selection. The empirical basis underlying Darwin's conclusions consisted of numerous observations made by him and other naturalists on the exquisite adaptations of animals and plants to their natural habitats and on the impressive results of artificial selection. Darwin fully appreciated the importance of heredity but was unaware of the nature and, in fact, the very existence of genomes. A century and a half after the publication of the "Origin", we have the opportunity to draw conclusions from the comparisons of hundreds of genome sequences from all walks of life. These comparisons suggest that the dominant mode of genome evolution is quite different from that of the phenotypic evolution. The genomes of vertebrates, those purported paragons of biological perfection, turned out to be veritable junkyards of selfish genetic elements where only a small fraction of the genetic material is dedicated to encoding biologically relevant information. In sharp contrast, genomes of microbes and viruses are incomparably more compact, with most of the genetic material assigned to distinct biological functions. However, even in these genomes, the specific genome organization (gene order) is poorly conserved. The results of comparative genomics lead to the conclusion that the genome architecture is not a straightforward result of continuous adaptation but rather is determined by the balance between the selection pressure, that is itself dependent on the effective population size and mutation rate, the level of recombination, and the activity of selfish elements. Although genes and, in many cases, multigene regions of genomes possess elaborate architectures that ensure regulation of expression, these arrangements are evolutionarily volatile and typically change substantially even on short evolutionary scales when gene sequences diverge minimally. Thus, the observed genome architectures are, mostly, products of neutral processes or epiphenomena of more general selective processes, such as selection for genome streamlining in successful lineages with large populations. Selection for specific gene arrangements (elements of genome architecture) seems only to modulate the results of these processes.     

Multilocus epimutations of imprintome in the pathology of embryo development

Genomic imprinting is one of the most significant epigenetic phenomena, which is involved in the support of eutherians and human embryo development. Molecular mechanisms of imprinting disturbance in the pathology of pre- and postnatal ontogeny are related to a considerable degree to aberrant DNA methylation of imprinted genes. At present time data about multiple abnormalities of DNA methylation arising simultaneously in several imprinted loci are accumulated. This fact brings up the problem of interpretation of imprintome structural and functional organization, as well as interaction of imprinted genes. At present study DNA methylation analysis of 51 imprinted genes in placental tissues of human spontaneous abortions was performed. The presence of several epimutations affected from four to 12 imprinted genes was observed in each embryo. Majority of epimutations (78%) had a postzygotic origin. It was shown for the first time that the total incidence of abnormal DNA methylation of maternal and paternal alleles of imprinted genes, which lead to suppression of embryo development, is significantly higher than the incidence of epimutations, which can lead to stimulation of ontogenesis processes. This fact supports at the epigenetic level the "sex conflict" hypothesis, which explains the appearance of monoallelic imprinted genes expression in the evolution of mammals.     

Rethinking the (im)possible in evolution

This paper will discuss the philosophical background to evolutionary theory and present multiple counterfactuals to each of the following seven empirically unsustainable but nonetheless widespread assumptions about genomic (DNA-based) evolution:1. “All heredity transmission occurs from parent to progeny”2. “Mutations are the result of inevitable replication errors”3. “Mutations occur at constant low probabilities over time” (= there are “mutation rates”)4. “Virus infection cannot induce genetic changes giving heritable resistance”5. “Mutations cannot be targeted within the genome”6. “Spontaneous hereditary changes are localized and limited to those of small effect”7. “Cells cannot integrate DNA change with biologically useful adaptive needs”.The summary take-home lesson is that we have to change from thinking of the genome as a read-only memory (ROM) that dictates the fate of the cell or organism to conceptualizing the genome as a read-write (RW) organelle modified transiently or permanently by the cell at different time scales.     

Gametic imprinting and expression of the gene Fused in the house mice

The discovery of the gametic imprinting phenomena in mammals makes it possible to have a new look at some facts concerning the expression and inheritance of genes with variable penetrance. Fused (Fu) is a dominant mutation located on chromosome 17, one of the few examples uses to demonstrate gametic imprinting in mice. This mutation has maternal effect connected with decrease in its penetrance. It was shown that t12 haplotype significantly reduces penetrance of the Fu in the progeny of Fu/t12 females. The results of reciprocal crosses of heterozygotes for t12 haplotypes indicate that penetrance of maternal Fu gene is reduced. Far more strong influence on the fused penetrance have the dominant suppressors, located beyond the chromosome 17. The penetrance of the fused gene decreases in that case up to 8-17%. Results of the experiments show strong influence of gametic pathway on penetrance of the gene by which the gene is transmitted to the next generation. The results also made it possible to describe the regularities of gametic imprinting. This phenomenon clearly indicates the existence of gametic and zygotic ontogenetic phases. According to the hypothesis proposed gametic phase of ontogenesis in mammals starts after initialization, i. e. after a process of chromosome erasing from epigenetic information and preparing to enter the next ontogenetic cycle.     

Blondes, lost and found: representations of genes, identity, and history

Research carried out during recent decades has revealed our genome not only to be a unique mine of information about health, disease and the human condition, but also about the origin and dispersal history of the species. In this context, the genome is simply an additional source of information about human history, epistemologically no different from other historical sources. However, media and public interpretation of genetic studies of human history are complicated by the wider connotations of genes as the determinants of hereditary features and identity. We discuss two examples of media and public fascination with the interrelated themes of history, identity and heredity, pointing out some implications of historical research using genetic data in the context of our own ongoing study of Inuit groups in Greenland and Victoria Island, Canada.     

From genetics of intraspecific differences to genetics of intraspecific similarity

Based on the Mendelian approach to heredity, modern genetics describes inheritance of characters belonging to the category of intraspecific difference. The other large category of characters, intraspecific similarity, stays out of investigation. In this review, the genome part responsible for intraspecific similarity is considered as invariant and regulatory. An approach to studying the invariant part of the Drosophila melanogaster genome is formulated and the results of examining this genome part are presented. The expression of mutations at genes in the invariant genome part is different from that of Mendelian genes. We conclude that these genes are present in the genome in multiple copies and they are functionally haploid in the diploid genome. Severe abnormalities of development appearing in the progeny of mutant parents suggest that the mutant genes are genes regulating ontogeny. A hypothesis on an elementary ontogenetic event is advanced and the general scheme of ontogeny is presented. A concept on two types of gene allelism (cis- and trans-allelism) is formulated. This approach opens a possibility for studying genetic material responsible for the formation of intraspecific similarity characters at different taxonomic levels on the basis of crossing individuals of the same species.