Mutations

By Aditey Nandan | 7 September 2024

_"It is not the strongest of the species that survives,_ _nor the most intelligent,_ _but the one that is most adaptable to change."_

~Charles Darwin

It would be only fair to credit Hugo de Vries, author of the book Mutation Theory, and who suggested the concept of genes, for first proposing the concept of mutations – single step but large changes in DNA – as the mechanism for evolution . One of his famous quotes says, “The main principle of the mutation theory is that species and varieties have originated by mutation, but are, at present, not known to have originated in any other way."

So, what exactly are mutations and why should study them?

Etymologically, the word ‘mutation’ comes from Latin word ‘mutare’ which means to change. Mutations are sudden changes in the DNA sequence of an organism. Mutations occurring in a gene can alter the functions of the protein it encodes. These changes can occur in many ways, primarily by altering the sequence of the nucleotides (building blocks of DNA), leading to changes in the genetic code.

It is important to understand that mutations are random in the sense they don’t occur to necessarily benefit or harm an organism. There are factors affecting the probability of a particular mutation taking place, however the impact of the mutation is not one of them. Only the mutations which occur in reproductive cells (called Germline Mutations) are passed to the next generation. These cells show about 100-200 mutations on average. What this means is that if we compare the DNA of the child and either of the parents, we will notice 100-200 changes which took place.

Mutations can occur in many ways, some of which are explained below:

  1. Point Mutations: These occur by affecting a single nucleotide, which is replaced by another.

  2. Frameshift Mutations: Addition or deletion of one or more nucleotide bases, that aren’t in multiples of three, changes the way the sequence is read during translation – since it is read in groups of three called codons.

Example: (the |xyz| represent one codon:)

Initial: ‘ATG GAA GUC CTT’ – |ATG|-|GAA|-|GUC|-|CTT| After Insertion: ‘ATG C GAA GUC CTT’ - |ATG|-|CGA|-|AGU|-|CCT|-|T…

  1. Inversion: When a segment of DNA is reversed from end to end.

  2. Translocations: Exchange of DNA segments between (non-homologous) chromosomes, which carry different genes normally.

Broadly speaking, since a mutation is an ‘error in DNA copying,’ it occurs when the replication mechanism breaks down or makes errors. There are systems in place to correct the mistakes made by a process called DNA repair,, but sometimes they escape it.

Mutations

Several factors, called mutagens, exacerbate the rate of mutations:

  1. Radiations: X-Rays, Gamma Rays, and other high energy radiations can cause breaks in DNA strands, leading to large scale mutations which can cause cancer (and unfortunately won’t make you the Hulk).
  2. Biological Agents: Some viruses, upon infection, can interfere with the genetic material, potentially leading to mutations.
  3. Environmental Factors: Exposure to carcinogens, pollution, chemicals etc.

Most mutations are neutral and have no significant impact on the body, however some mutations do have effects. These may be beneficial – some mutations in bacteria help them develop antibiotic resistance. Some mutations can be extremely harmful, and can cause diseases like cancer or genetic disorders like cystic fibrosis and Huntington’s disease.

Mutations are critical for evolution and are the primary source for genetic variation. These variations allow organisms to adapt in a changing environment. However, mutations are not always beneficial and can lead to various disorders. Understanding mutations is key to advances in medical sciences. There is also work being done to manipulate these mutations.  

References:

  1. Dolgin, E. Human mutation rate revealed. Nature (2009)
  2. Eyre-Walker, A., & Keightley, P. D. The distribution of fitness effects of new mutations. Nature Reviews Genetics 8, 610–618 (2007) doi:10.1038/nrg2146
  3. Orr, H. A. The genetic theory of adaptation: A brief history. Nature Review Genetics 6, 119–127 (2005) doi:10.1038/nrg1523
  4. Sandelin, A., et al. Arrays of ultraconserved non-coding regions span the loci of key developmental genes in vertebrate genomes. BMC Genomics 5, 99 (2004)
  5. Hershberg R. (2015). Mutation--The Engine of Evolution: Studying Mutation and Its Role in the Evolution of Bacteria. Cold Spring Harbor perspectives in biology, 7(9), a018077. https://doi.org/10.1101/cshperspect.a018077

Back