Random changes in the genetic material are the driving force of evolution. But what is the natural frequency of mutations that occur in our cells?

Offspring inherit their traits through a combination of genetic material from both parents - half from the mother and half from the father. However, sometimes random changes, called mutations, which were not present in the parents’ code, occur in the inherited genetic code. These mutations are the driving force of evolution, as they introduce genetic variations between individuals that natural selection can act upon. While some mutations may be beneficial and contribute to an individual’s survival or reproduction, others may significantly impair the ability of the individual to survive. Many mutations are neutral and do not confer advantages or disadvantages in the current environmental conditions. But how common are mutations, really?

The causes of mutations are numerous. In some cases, external factors such as certain chemical substances or high-energy (ionizing) radiation, such as radioactive radiation, can break or alter DNA. In other cases, mutations may arise from internal factors within the cell, such as oxygen reactive species that are generated by cellular activity, or errors in the process of DNA replication during cell division.

In an ongoing long-term study that was initiated in 1988, Richard Lenski, an evolutionary biologist from Michigan State University in the United States, followed 12 cultures of the bacteria Escherichia coli (E. coli). Using gene sequencing technology (DNA sequencing), he compared the changes that occurred in the genetic code of the bacteria in the cultures over more than 70,000 generations. His finding indicated that the natural mutation rate of the bacteria is one mutation per ten billion base pairs, which form the fundamental building blocks of the genetic code. This implies that the bacterium, which has a total of about five million base pairs, undergoes one mutation approximately every thousand generations, which equates to one thousand cell divisions. Considering that the culture contains billions of bacteria, there is a high probability of a mutation occurring in almost every base of the genome.

However, it’s worth noting that this experiment does not account for lethal mutations that can cause the death of the bacteria carrying them, resulting in their disappearance from the culture, and hence cannot be sequenced. Additionally, mutations that negatively affect the growth rate of the bacteria will also go undetected in the experiment, as the more successful cells will dominate the culture. In fact, the experiment only measures the average mutations occurring across the entire population over thousands of generations. Therefore, the mutation rate of an individual dividing bacterium remains unknown.


יכולה להתרחש באקראי או בעקבות חשיפה לקרינה וכימיקלים. מוטציה נקודתית | איור: Science Photo Library
A mutation can occur randomly or following exposure to radiation and chemicals. A single mutation | Illustration: Science Photo Library

The Mutation Rate Per Division

Can we determine the rate of mutation in individual cells, including that of detrimental mutations? To investigate this, microbiologists Marina Elez, Lydia Robert, and their colleagues from the University of Sorbonne in Paris utilized a technology known as microfluidics, which involves a narrow tube system with a width comparable to that of a single E.coli bacterium. The system enables the scientists to supply into the tubes nutrients that can sustain the trapped bacteria and allow them to monitor the growth rate, division rate, or death of the bacteria under a microscope.

Additionally, the cells contain a biochemical fluorescent marker, which is activated every time an error occurs in DNA during cell division. Consequently, the researchers can track not only the cells that divide after the marker is triggered, but also those that grow or divide slowly after the mutation emerges, as well as those that stop dividing (i.e., die) because of it. 

The experimental results indicated that the mutation rate was about 0.1 percent per generation, which translates to one mutation in every thousand bacterial divisions. This finding is consistent with Lensky’s discovery. Out of all mutations, one percent were lethal, and an additional 0.3 percent substantially reduced the cell growth rate. The vast majority of the mutations were neutral.

How does the mutation rate in humans compare to that of bacteria? Studies that compared the genetic sequence of two parents and their offspring, as well as large populations, have shown that the mutation rate is roughly 1 per 100 million bases per generation, resulting in 10-20 mutations between parent and child in each generation. The reason for the discrepancy in the number of mutations per generation between bacteria and humans can be attributed to the fact that the human genome is nearly a thousand times larger than that of bacteria, with approximately three billion bases. Moreover, while one generation of bacteria spans a single cell division, humans are multicellular organisms, and a "generation" encompassess about 20-30 cell divisions to form an egg cell in the mother (and roughly ten times that to form a sperm cell in the father). Calculations based on these figures suggest that the rate of mutations in humans is actually comparable to that of bacteria, ranging from 1 in a billion to 1 in ten billion bases per cell division. Similar observations have been made in laboratory mice, fruit flies (Drosophila), and Arabidopsis plants.