Heredity determined by the environment: Lamarckian ideas in modern molecular biology.

Inheritance of acquired characteristics (IAC) is a well-documented phenomenon occurring both in eukaryotes and prokaryotes. However, it is not included in current biological theories, and the risks of IAC induction are not assessed by genetic toxicology. Furthermore, different kinds of IAC (transgenerational and intergenerational inheritance, genotrophic changes, dauermodifications, vernalization, and some others) are traditionally considered in isolation, thus impeding the development of a comprehensive view on IAC as a whole. Herein, we discuss all currently known kinds of IAC as well as their mechanisms, if unraveled. We demonstrate that IAC is a special case of genotype × environment interactions requiring certain genotypes and, as a rule, prolonged exposure to the inducing influence. Most mechanisms of IAC are epigenetic; these include but not limited to DNA methylation, histone modifications, competition of transcription factors, induction of non-coding RNAs, inhibition of plastid translation, and curing of amyloid and non-amyloid prions. In some cases, changes in DNA sequences or host-microbe interactions are involved as well. The only principal difference between IAC and other environmentally inducible hereditary changes such as the effects of radiation is the origin of the changes: in case of IAC they are definite (determined by the environment), while the others are indefinite (arise from environmentally provoked molecular stochasticity). At least some kinds of IAC are adaptive and could be regarded as the elements of natural selection, though non-canonical in their origin and molecular nature. This is a probable way towards synthesis of the Lamarckian and Darwinian evolutionary conceptions. Applied issues of IAC are also discussed.

The Problem of Non-Shared Environment in Behavioral Genetics.

The role of non-shared environment (NSE) in the development of psychological traits is usually comparable with that of the genotype. However, no specific factors of NSE with significant impact on such traits have been discovered so far. We propose that the current failures in understanding the origin of NSE are at least partly due to the fact that behavioral genetics has left out one of the key sources of phenotypic variation. This source is the intrinsic stochasticity of molecular processes underlying individual development. At the critical stages of ontogeny, even minor fluctuations in gene expression or gene-product functioning can remarkably affect the phenotype; this role is experimentally proved in multiple model organisms. In the present paper, several mechanisms of molecular stochasticity, which could affect the development of psychological traits, are discussed. We propose to distinguish external NSE (any external differences) and internal NSE (intrinsic molecular stochasticity). Available data indicate that the impact of external NSE is likely to be low, which makes the presumptive role of internal NSE rather decisive. If our assumption is true, the paradigm of behavioral genetics should be revised, and comprehensive analysis of molecular stochasticity during individual development is strongly required.

The mechanisms of epigenetic inheritance: how diverse are they?

Although epigenetic inheritance (EI) is a rapidly growing field of modern biology, it still has no clear place in fundamental genetic concepts which are traditionally based on the hereditary role of DNA. Moreover, not all mechanisms of EI attract the same attention, with most studies focused on DNA methylation, histone modification, RNA interference and amyloid prionization, but relatively few considering other mechanisms such as stable inhibition of plastid translation. Herein, we discuss all known and some hypothetical mechanisms that can underlie the stable inheritance of phenotypically distinct hereditary factors that lack differences in DNA sequence. These mechanisms include (i) regulation of transcription by DNA methylation, histone modifications, and transcription factors, (ii) RNA splicing, (iii) RNA-mediated post-transcriptional silencing, (iv) organellar translation, (v) protein processing by truncation, (vi) post-translational chemical modifications, (vii) protein folding, and (viii) homologous and non-homologous protein interactions. The breadth of this list suggests that any or almost any regulatory mechanism that participates in gene expression or gene-product functioning, under certain circumstances, may produce EI. Although the modes of EI are highly variable, in many epigenetic systems, stable allelic variants can be distinguished. Irrespective of their nature, all such alleles have an underlying similarity: each is a bimodular hereditary unit, whose features depend on (i) a certain epigenetic mark (epigenetic determinant) in the DNA sequence or its product, and (ii) the DNA sequence itself (DNA determinant; if this is absent, the epigenetic allele fails to perpetuate). Thus, stable allelic epigenetic inheritance (SAEI) does not contradict the hereditary role of DNA, but involves additional molecular mechanisms with no or almost no limitations to their variety.

Allelic variants of hereditary prions: The bimodularity principle.

Modern biology requires modern genetic concepts equally valid for all discovered mechanisms of inheritance, either "canonical" (mediated by DNA sequences) or epigenetic. Applying basic genetic terms such as "gene" and "allele" to protein hereditary factors is one of the necessary steps toward these concepts. The basic idea that different variants of the same prion protein can be considered as alleles has been previously proposed by Chernoff and Tuite. In this paper, the notion of prion allele is further developed. We propose the idea that any prion allele is a bimodular hereditary system that depends on a certain DNA sequence (DNA determinant) and a certain epigenetic mark (epigenetic determinant). Alteration of any of these 2 determinants may lead to establishment of a new prion allele. The bimodularity principle is valid not only for hereditary prions; it seems to be universal for any epigenetic hereditary factor.