epigenetic mechanisms

Genetic expression has traditionally been understood as one gene-one protein, however, much genetic expression is regulated through reversible and transmissable epigenetic mechanisms, which act without an alteration of archival DNA.

Epigenetics includes the phenomenon within molecular genetics whereby a single sequence of DNA can give rise, through alternative splicing, to multiple versions of mRNA, and hence to multiple proteins, thus increasing complexity and fine-tuning genetic expression. Epigenetics also refers to DNA related mechanisms of inheritance, such as methylation and chromatin assembly.

Epigenetic regulation of gene expression is mediated through alterations in DNA methylation , covalent modifications of core nucleosomal histones, rearrangement of histones, transposon function, chromosome imprinting, type switching, telomeric silencing, and by RNA interference.

Genomic imprinting is a form of mammalian epigenetic regulation which results in the silencing of one copy (allele) of specific genes, according to parental origin. Recently, protein complexes have been discovered to manipulate nucleosomes, organize larger chromatin domains, and set boundaries of chromatin structure. Thus, key histone modifications, cis-acting elements, and regulatory proteins set, maintain, and reprogram epigenetic memory.

Epigenetic mechanisms also operate as conditional, non-programmed interactions that determine individual development [s]:
1. Interactions of cell metabolism with the external and internal physicochemical environment of an organism.
2. Interactions of tissue masses with the physical environment on the basis of physical laws inherent to condensed materials.
3. Interactions among tissues themselves.

Deregulation of epigenetic mechanisms cooperates with genetic alterations in the development and progression of malignancies. Loss of epigenetic regulation is also implicated in systemic disease. Epigenetic deregulation affects several aspects of the biology of tumor cells, including cell cycle control, differentiation, cell growth, DNA repair, and cell death.

In plants, epigenetic alterations that occur during somatic growth can be transmitted to the progeny because germ cells differentiate from somatic tissues only after many cycles of mitotic divisions.

Defining epigenetic states through chromatin and RNA - Nature Genetics: "The term 'epigenetics' is used to describe heritable changes in genome function that occur without a change in DNA sequence. As such, epigenetics lies at the heart of the cellular memory crucial for development and provides an important avenue for sustained response to environmental stimuli."

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External : Transposons part 1, transposons part 2 : Barbara McClintock and mobile genetic elements :

genetic variation

Genetic mutations involve structural, usually transmissible change in DNA or RNA within a cell or organism. Somatic mutations affect the cells of an organism, yet are not trasmitted to the next generation unless they affect the germline, those zygotes, such as ova and sperm that are committed to reproduction. Transmissible mutations affect the germline or result from errors during replication and cell division during reproduction.

Sequence mutations result from nucleotide substitutions, insertions, deletions, or re-arrangements of gene segments. On a larger scale, chromosomes are altered during replication and cell division by deletion, duplication, inversion, recombination, translocation, transposition, and non-disjunction.

Depending upon their effects upon an organism within a particular environment, mutations may be neutral, beneficial, or deleterious. The commonest mutations affect single nucleotides (point mutations or SNPs). Because the genetic code is redundant, many single nucleotide substitutions are neutral.

The genetic makeup of descendent diploid populations differs from that of the parental population by virtue of recombination, the random shuffling of genes during meiosis.

Insertion of mobile genetic elements, transposons and retrotransposons, increases genetic variability. The human genome, for example, includes approximately 500,000 Alu elements located within introns, and 25,000 of those could become new exons, coding for polypeptide sequences, by undergoing a single-point mutation.

As a result of alternative splicing, mutations that alter a splice site or a nearby regulatory sequence can have subtle effects by shifting the ratio of the resulting proteins without entirely eliminating any form. Alternative splicing also generates new polypeptide combinations from already existing code. Recently, researchers have demonstrated that modification of regulation of a single gene has enabled rapid phenotypic speciation in sticklebacks.

Alternative promoters enable mammals to extract more variability from fixed DNA sequences by regulating location and timing of transcription, adjusting the timing of protein production or generating alternative proteins by modifying the location at which transcription commences. Roughly 40-50 % of human and mouse genes have alternative promoters, which are more active during embryological development, and which display evolutionary conservation.

Statistical, population mechanisms operate upon allele frequencies within populations. Natural selection involves transmission of gene combinations that derived from parental genotypes that have proven favorable to survival and to reproductive success. Purely random bottleneck and randomly isolated founder effects are mechanisms of genetic drift, the random transmission of alleles between generations. Gene flow refers to the movement of genes from the gene pool of one population into that of another, brought about by movement of individual animals, gametes, or spores. Gene flow increases biodiversity and acts against speciation pressures by rendering two populations more similar to each other.