Epigenetics | Inheritance matters more than DNA

Epigenetics deals with the study of heritable phenotypic changes that do not involve changes in the DNA sequence.

Molecular basis of Epigenetics

  • Epigenetics, the study of the chemical modification of specific genes and ultimately their associated proteins in an organism. These modifications define how the genetic information in the genes is expressed and used by cells.
  • Epigenetics most often denotes changes that affect gene activity and how they express themselves in cells, but can also be used to describe any heritable phenotypic change.
  • These effects on cellular and physiological phenotypic trait may result from any environmental or external factors or may be part of normal development. All of these epigenetic modifications are heritable either in the progeny of cells or of organisms.
  • The mechanisms that produce such changes are DNA methylation and histone modification, each of which alters how genes are expressed without altering the DNA sequence.

Epigenetics in Development

During the development of multicellular organism especially in morphogenesis, totipotent stem cells become the various pluripotent cell lines of the embryo which ultimately becomes fully differentiated cells.

In other words, when the zygote continues to divide, the resulting cells change into all other different cell types by activating some genes while inhibiting the expression of others.

Epigenetics & Evolution

Epigenetically Inherited Licking and Grooming (LG) behaviour
Epigenetically Inherited Licking and Grooming (LG) behaviour
  • Humans and apes share 99% of their DNA but still, we seem different species, Right!
  • So, epigenetic modifications are game changer behind that. Despite, these fancy apes having the same genes, it is not the protein sequences that account for the differences in phenotypic characteristics between humans and apes; rather, methylation differences are what account for phenotypic variations.
  • There are also several genes that are conserved at the protein level between human and chimpanzees but have epigenetic modifications.

The key point is that all these epigenetic modifications which have some utility can be inherited and play a key role in designing evolution.

An outstanding example of this comes from the licking and grooming literature in rats, which shows that the level of licking and grooming experienced by a pup becomes an epigenetically inherited part of their own maternal behavioural phenotype and is passed on to a number of generations. So, a mutation in the genomic sequence is not required for a heritable change.

Epigenetic Reprogramming of Somatic cells

Genetically identical mice with different DNA methylation patterns causing imperfection in the tail of one but not the other.
Genetically identical mice with different DNA methylation patterns causing imperfection in the tail of one but not the other. (Photograph courtesy of Emma Whitelaw, University of Sydney, Australia.) [CC BY 2.5], via Wikimedia Commons
  • Epigenetic machinery combines multiple networks of proteins that are interconnected through functional and physical interactions to write, read and edit genetic information either by DNA methylation or by histone modification, thus allow dynamic regulation of gene expression.
  • Somatic cells are characterized by stable chromatin environment, responsible for silencing and inactivating genes that are not specific for a particular cell type.
  • Compared to somatic cells, pluripotent stem cells possess an open and active chromatin modification.
  • In order to actual reprogramming of somatic cells in pluripotent cells i.e. Induced pluripotent stem cells (iPSCs), several epigenetic factors are involved. It has been proposed that certain epigenetic factors really work to erase the original somatic epigenetic marks to acquire the new epigenetic marks that are part of the aim to achieve a pluripotent stage.

Transgenerational Epigenetic Inheritance

  • Transgenerational epigenetic inheritance is the transmission of epigenetic information and modification from one generation to next i.e. (parent-offspring transmission).
  • Ok, there is a lot of chaos around it as in mammals epigenetics marks are erased which is what we call “reprogramming“. (Don’t confuse somatic cell reprogramming with transgenerational epigenomic reprogramming).
  • The first erasure occurs just after fertilization, in the zygote to clear gametic epigenomic marks. During this phase of reprogramming, genetic imprints are maintained.
  • Other epigenetic erasure occurs in the germline (primordial germ cells or future gametes) where parental somatic programs are erased.
Suppressed gene expression by DNA Methylation
Suppressed gene expression by DNA Methylation

Reprogramming is required to remove epigenetic marks inherited from parents so that embryo properly reflects genetic blueprint of each species and if reprogramming fails epigenetic signatures can be retained and could be transmitted from one generation to the next.

But epigenetic inheritance is mostly deleterious or neutral. Indeed, transgenerational epigenetic inheritance has also the potential to be adaptive, and in some scenarios, might even respond to nature (natural selection), with major implications for evolution.

just bunch of cells studying cells🔬📒


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