What is the Difference Between DNA Sequence Mutations and Epigenetic Modifications

The main difference between DNA sequence mutations and epigenetic modifications is that the DNA sequence mutations result in the changes in the genetic information whereas the epigenetic modifications result in the modifications of gene expression. 

DNA sequence mutations and epigenetic modifications are two types of alterations in the structure of the genome. DNA sequence mutations cannot be reversed while epigenetic modifications can be reversed. 

Key Areas Covered

1. What are DNA Sequence Mutations
     – Definition, Types, Effect on the Genome
2. What are Epigenetic Modifications
     – Definition, Types, Effect on the Genome
3. What are the Similarities Between DNA sequence Mutations and Epigenetic Modifications
     – Outline of Common Features
4. What is the Difference Between DNA sequence Mutations and Epigenetic Modifications
     – Comparison of Key Differences

Key Terms

Chromosomal Mutation, DNA Sequence Mutation, Epigenetic Modification, Frame Shift Mutation, Gene Expression, Point Mutation, Reversibility, Structural Modifications of DNA

What are DNA Sequence Mutations

DNA sequence mutations are the permanent alterations of the nucleotide sequence of the genome. They, in turn, alter the function of the expressed proteins by changing the amino acid sequence. Moreover, there are three possible types of DNA sequence mutations:

Point Mutations

These are the alterations of a single nucleotide in the DNA sequence. The three types of point mutations are missense mutations, nonsense mutations, and silent mutations. Missense mutations occur by the substitution of a single nucleotide in the gene sequence, which in turn change a single amino acid of the expressed protein. On the other hand, nonsense mutations are the substitutions of a single nucleotide in the gene sequence, introducing a stop codon, which in turn stops the transcription. In addition, silent mutations are a substitution of a single nucleotide in the gene sequence, which still represents the same amino acid based on the degeneracy of the genetic code.

Figure 1: Point Mutations

Frame Shift Mutations

These mutations alter the open reading frame of the gene. There are three types of frame shift mutations as insertions, deletions, and duplications. An insertion is the addition of one or a few nucleotides to the gene sequence while deletions are the removal of one or several nucleotides from the gene sequence. In contrast, duplications are the copying of a part of DNA one or more times within the gene.

Figure 2: Frame Shift Mutations

Chromosomal Mutations

These mutations make considerable changes in the genomic DNA. Furthermore, the five types of chromosomal mutations are translocations, gene duplications, intra-chromosomal deletions, inversions, and loss of heterozygosity. 

Figure 3: Chromosomal Mutations

In translocations, parts of chromosomes are interchanged between nonhomologous chromosomes whereas, in gene duplications, a particular allele occurs in multiple copies within the genome, increasing the gene dosage. Moreover, in intra-chromosomal deletions, a segment of a chromosome can be removed. Inversions, on the other hand, are the changes in the orientation of a chromosome segment. Meanwhile, the loss of an allele from one of the homologous chromosomes causes the loss of Heterozygosity.

What are Epigenetic Modifications

Epigenetic modifications are the alterations of the chromatin structure, which cause the heritable changes in the gene expression. The main feature of epigenetic modifications is that they do not alter the nucleotide sequence of the gene. Further, the three main types of epigenetic modifications are DNA methylation, histone modification, and non-coding RNA based transcriptional gene silencing.

DNA Methylation

DNA methylation is always associated with the activation and repression of genes. During this process, a methyl group is added to the 5’ position of the cytosine nucleotide next to the guanine nucleotide, which is linked by a phosphate group. This forms the CpG dinucleotide. The enzyme involved in this process is DNA methyltransferases. This methyl group acts as an epigenetic factor, which marks the genes as active or inactive.

Figure 4: Epigenetic Modifications

Histone Modifications

Different types of histone modifications including acetylation, deacetylation, and histone methylation are responsible for the binding of the epigenetic factors to the tails of the histones. This alters the extent of wrapping of DNA around histone molecules, which in turn alter gene expression. Moreover, there are two types of chromatin, according to their degree of wrapping. They are euchromatin and heterochromatin. In euchromatin, the DNA is loosely wrapped; hence, the genes in the euchromatic regions are actively expressing. In contrast, heterochromatin contains tightly wrapped DNA around histones and the genes in the heterochromatic regions are inactive by means of transcription and genetics.

Figure 5: Euchromatin and Heterochromatin 

Non-coding RNA based Transcriptional Gene Silencing

The mi-RNAs (micro-ribonucleic acids), the short nucleotides derived from the introns of protein-coding genes or transcribed from independent genes serve as regulators in the signalling pathways, which block translation.

Similarities Between DNA sequence Mutations and Epigenetic Modifications

• DNA sequence mutations and epigenetic modifications are the two types of structural modifications that can occur in the DNA of the genome.
• They are capable of exerting alterations in gene product.
• In addition, both types of alterations are heritable.

Difference Between DNA Sequence Mutations and Epigenetic Modifications

Definition

A DNA sequence mutation refers to a permanent alteration in the DNA sequence that makes up a gene so that the sequence differs from what is found in most the organisms while an epigenetic modification refers to a heritable alteration in gene expression and cellular function without changes to the original DNA sequence. This is the basic difference between DNA sequence mutations and epigenetic modifications.

Occurrence

Moreover, DNA sequence mutations occur due to errors in DNA replication or by the effect of mutagens while epigenetic modifications occur due to environmental factors including diet and exposure to certain chemicals.

Structural Alteration

Another difference between DNA sequence mutations and epigenetic modifications is that DNA sequence mutations are the alterations of nucleotide sequences of genes while epigenetic modifications are the alterations in the accessibility of DNA and chromatin structure.

Functional Alteration

DNA sequence mutations change the amino acid sequence of the protein while epigenetic modifications change gene expression. This is another difference between DNA sequence mutations and epigenetic modifications.

Types

The three main types of DNA sequence mutations are point mutations, frame shift mutations, and chromosomal mutations while the three main types of epigenetic modifications are DNA methylation, histone modification, and non-coding RNA-based transcriptional gene silencing.

Reversibility

Furthermore, reversibility is a major difference between DNA sequence mutations and epigenetic modifications. DNA sequence mutations are irreversible while epigenetic modifications are reversible.

Conclusion

DNA sequence mutations are the alterations in the nucleotide sequence of a gene, which results in a protein with an altered amino acid sequence. This may change the function of the protein and produce a new trait. Furthermore, when it is inherited, DNA sequence mutations are irreversible. Epigenetic modifications, on the other hand, are changes in the chromatin structure which alters the accessibility to DNA. This alters gene expression. However, epigenetic modifications are reversible. Therefore, the main difference between DNA sequence mutations and epigenetic modifications is the type of alteration in the DNA structure and their role.

Reference:

1. “What Kinds of Gene Mutations Are Possible? – Genetics Home Reference – NIH.” U.S. National Library of Medicine, National Institutes of Health, Available Here
2. Handy, Diane E et al. “Epigenetic modifications: basic mechanisms and role in cardiovascular disease” Circulation vol. 123,19 (2011): 2145-56. Available Here

Image Courtesy:

1. “Different Types of Mutations” By Jonsta247 (CC BY-SA 4.0) via Commons Wikimedia  
2. “Frameshift deletion (13062713935)” By Genomics Education Programme – Frameshift deletion (CC BY 2.0) via Commons Wikimedia  
3. “Chromosomes mutations-en” By GYassineMrabetTalk✉This W3C-unspecified vector image was created with Inkscape. – Own work based on Chromosomenmutationen.png (Public Domain) via Commons Wikimedia  
4. “Epigenetic modifications” By AJC1 (CC BY-SA 2.0) via Flickr
5. “Sha-Boyer-Fig1-CCBy3.0” (CC BY 3.0) via Commons Wikimedia  

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