Mutations: the navigators in the evolutionary journey

Divya Vishwanath

A team of scientists from the National Centre for Biological Sciences (NCBS), Bengaluru, has discovered that mutations not only provide genetic variation but also actively influence evolution, aiding organisms in adapting to new environments. Their study on E. coli revealed that altering mutation biases can lead to a greater number of beneficial mutations, providing new insights into evolution.

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Mutations are changes in the DNA sequence of an organism. They are the source of genetic variation; but changes brought about by mutations are often regarded as random. However, scientists from the National Centre for Biological Sciences (NCBS), Bengaluru, and Western University, Canada, have made a significant discovery regarding the role of mutations in evolution. Their research has revealed that mutations not only provide the fundamental material for evolution but also actively influence the types of mutations that occur. This can aid organisms in adapting to new environments and drive the evolutionary process.

Deepa Agashe, Associate Professor, NCBS, Bengaluru, who is also one of the corresponding authors of the study, said, Our research lab has been studying how mutations contribute to adaptation for a while. When some kinds of mutations are favoured over the others, it is termed as a mutation bias. We started this project to see if changing the mutation bias affects an organism’s ability to adapt and how bacterial genomes evolve. Previous studies hadn’t looked at the impact of intentionally causing certain types of mutations more than others.”

The researchers conducted this study on a bacterium known as Escherichia coli (E. coli). They designed experiments and used computer simulations, drawing on their knowledge of how this bacterium has evolved over time. They worked with two types of E. coli cells: the normal cells (referred to as wild type or WT) and a modified version (referred to as Δ mut Y), which was created by removing a gene responsible for DNA repair. The researchers isolated colonies from both strains and performed a technique called whole genome sequencing (WGS) on them. This method allowed them to determine the complete DNA sequence of the E. coli genome, which consists of about 4 – 5 million building blocks called nucleotides.

By performing WGS, the team identified clones that differed from the original WT or Δ mut Y by a single mutation. This process also allowed them to determine the mutational spectra (complete range of mutations in a gene or organism) of the different strains and calculate mutational bias metrics. However, conducting this type of study on such a large scale presented its own challenges. Agashe said, To find the set of mutations we needed, we had to generate, sequence, and sift through three times as many strains. We were lucky to strike up a wonderful collaboration with Professor Wahl, a mathematician in Canada whose intuition and extensive simulations helped interpret our results.” 

The team of scientists discovered that some mutations occurred more frequently than others, enabling the bacteria to adapt to changes in its environment. Until now, the role of mutations in evolution has been underestimated. It was believed that mutations simply provided genetic variation, which was then spread through reproduction, and natural selection determined whether the new trait would persist or disappear. However, this study has revealed that mutations play a much more active role.

Sutirth Dey, Professor, Indian Institute of Science, Education and Research (IISER), Pune, elaborated, It was known that changes in certain genes could alter the mutation rates of organisms. Sane et. al. have proven that these changes can also modify the profile of mutations that are available to an organism, which will affect evolution in a different way. They have shown that this altered profile will lead to a greater number of beneficial mutations being accessible to the organism – something that I would not have guessed prior to this study.”

The findings open up new directions for the team to explore. Our study indicates that reversing an existing mutation bias should always be beneficial and drive species to adapt to new environments. We have tested this using several strains with varying mutation spectra, and the results are quite intriguing. However, we are conducting further research to solidify our findings. We have planned more projects to test the evolutionary effects of mutation biases over the next few years”, said Agashe.

Written By

Divya is a scientist by passion and profession, and possesses a deep love for reading and learning. Writing is her way of translating the thoughts and questions in her head into a structured form to help her learn more.