How Mutations Lead to Genetic Disease and Adaptation

Mutations are any change in the DNA. DNA is the genetic material containing all the information to make and enable a living cell to function. Because of this, changes in the DNA can lead to changes in how the cell functions. Great if it then makes the cell work better, but not so great if it leads to disease.

In the last post, I explained what mutations are and the different types. This post will focus on how genetic mutations can be harmful and lead to genetic disease. Mutations can also be beneficial, helping organisms adapt to their environment.

Mutations and Disease

Genetic disorders are caused by one or more mutations that alter the function of proteins which play a critical role in the body.

An example of a genetic disease caused by the smallest change is sickle cell anaemia. This disease is caused by a point mutation in the haemoglobin gene. This gene encodes the haemoglobin protein that carries oxygen in red blood cells. A single nucleotide, thymine, is replaced by adenine. The result is an abnormal sickle-shaped haemoglobin protein, as shown in Figure 3 below. When oxygen levels are low, their sickle-shaped haemoglobin aggregates together and can clog up small blood vessels (Figure 3B). This can cause symptoms such as physical weakness, pain and organ damage.

Sickle cell anaemia

In some cases, a person may not be born with a disease but may be more susceptible to getting the disease due to the presence of one or more gene mutations. Examples of such disease are cancer and diabetes. Other genetic diseases are not inherited but are caused by mutations gained during their lifetime.

Mutations that lead to disease are actually quite rare events. Most mutations have no impact on health or development. Besides, our cells have an efficient DNA Repair mechanism that is able to recognise most forms of DNA mutations and then repair the damage before it can lead to a genetic disease.

Are all mutations bad?

No, not all mutations are bad. Some mutations can actually be beneficial. Mutations can give rise to characteristics that allow an organism to adapt better to its changing environment. This was first described by Charles Darwin as adaptation. These new changes are then passed through the generations, giving their offspring an advantage over others for survival and reproduction in a particular environment.

Remember, mutations can only be inherited if they occur in the gametes. Advantageous mutations that occur in other cells are lost when that individual dies.

What is Natural Selection?

Natural selection is the mechanism of adaptation. It is the process that drives evolution. And it is only possible through mutations and sexual reproduction. Both Charles Darwin and Alfred Russel Wallace are credited for the theory of evolution by natural selection. A few years later, Gregor Mendel discovered that natural selection was an inherited process.

Mutations that give a species advantage over others in its environment will influence the future of that species. But the goal of natural selection is not to make the perfect bacteria, plant or animal. It is to provide the best advantage for a species in response to environmental factors that change from place to place and over time.

Because the rate of mutations is so low in animal and plant cells, it can take hundreds or thousands of years for significant changes in genetic characteristics. And as the advantageous characteristic is passed through the generations, it becomes more common in populations.

We see the results of natural selection all around us. For example, the colour of the fur on polar bears (white) and grizzly bears (brown) gives each the best camouflage in their environment. Or the changes in beak size and shape in species of finches, a type of bird found in the Galapagos Islands. These changes help the different finches to adapt to their different diets (Grant, 1993 - https://royalsocietypublishing.org/doi/10.1098/rstb.1993.0052).

Galapagos Island Finches

For example, the medium ground finch (Geospiza fortis) have large beaks to help them to crack and eat large seeds (Figure 4A). On the other hand, the cactus finches (Geospiza scandens) have narrow and pointed beaks that help them to eat the flowers and fruit of cactus (Figure 4B).

Why are Genetic Diseases not Removed by Natural Selection?

If natural selection helps to select for mutations that give an organism an advantage, you might also expect that natural selection would remove mutations in the populations that are harmful. Why genetic diseases are not selected against is not so simple and there are several reasons why a disease will persist in a population.

Let’s go back to the example of sickle cell anaemia to explain why this may be the case. This disease is prominent in people with ancestors from sub-Saharan Africa, India, the Mediterranean countries and the Middle East. Sickle cell anaemia is a recessive genetic disease. This means that you need to inherit two copies of the mutated gene to have the disease. Having only one mutated copy of the gene does not result in the disease. But a person with this one mutated copy is resistant to malaria, a potentially lethal disease prevalent in these countries. In many sub-Saharan Africa countries, between 10-45% of people are carriers of one mutated gene. The number decreases to <1% in South Africa and <2% in North African countries (WHO Statistics - https://apps.who.int/iris/bitstream/handle/10665/1682/AFR-RC60-8.pdf?sequence=1&isAllowed=y). This distribution shows an advantage of having one copy of the sickle-cell gene mutation in areas where there is high risk of malaria transmissions, as it offers protection against malaria to the population.

Malaria transmission in the world

Figure 5: Geographical Areas of Malaria Transmission by CDC / CC (https://creativecommons.org/licenses/by/3.0)

Figure 5, from the Centre of Disease Control (CDC), shows the malaria transmissions in the world, with sub-Saharan Africa with the highest rates.

In conclusion, a mutation is a change in the DNA. They can occur spontaneously, albeit at a very low rate, or be induced by mutagens such as UV light.

When a mutation does happen, the result can vary. Most mutations will go unnoticed. Other mutations can have a huge effect such as causing inherited diseases. And some mutations can also have a positive effect. Over time, these mutations can lead to diversity in species.  

Other related posts we think you might like: Sunlight and Your Skin, and Emerging Viruses.

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