Beneficial Mutations

When we think of mutants and mutations, perhaps our initial thoughts lead us to images of theatrical monsters made from laboratory mishaps. Slime green fluorescing creatures made from the accidental mixing of buckets of radioactive goo, may be the very picture of mutants in our minds. Yet, these images are largely just the stereotypes that we arrive at from the films, literature, and culture we've consumed over the years. In reality, mutations are rarely so dramatic. Mutations are also not always harmful, in fact, some are distinctly beneficial.

Beneficial genetic mutations

How can we understand the concept of beneficial mutations at the genetic level? First, let us examine DNA. DNA is comprised of a phosphate backbone with attached nucleosides. These nucleosides potentially include adenosine, thymine, guanine, and cytosine, and these four form hydrogen bonds between each other that help them to intercalate and allow for the classic DNA double-helix coil.

When a length of DNA with a known sequence of nucleotides (which are nucleosides + their phosphate backbone) has an alteration in a particular (or multiple) nucleotide, this is a mutation. So, for example, if at position 7 in a gene there is meant to be a thymine (T) nucleotide, and instead there appears through an error of DNA replication (usually committed by the enzyme DNA polymerase) a cytosine (C) nucleotide; this is a mutation (Fig. 1). Sometimes a single nucleotide gets switched for another, as in our above example - this is termed a point mutation because the error or switch or mutation occurs at a single point.

Fig. 1: Point mutation. YourGenome.

Sometimes multiple nucleotides in sequence are altered from the original, intended strand; and this collection of alterations can be termed a mutation as well.

Now, how do we know when one of these mutations is beneficial just from looking at its sequence? Well, we cannot. A beneficial mutation is one that confers positive qualities; especially increased fitness, to the organism that has it. Beneficial mutations are not the most common in nature, but when they do occur, they tend to propagate at a higher rate than random through the population. This may be due to natural selection.

Beneficial mutations in humans

Now that we understand what beneficial mutations are on a genetic level, let's dig deeper and discover some beneficial mutations that exist in our world. We will look specifically at beneficial mutations in humans. Some of these include:

• Lactose tolerance:

  • Would you believe that your ability (if you have it, as large swathes of the world's population are lactose intolerant) to happily imbibe milk, ice cream, and cheeses while remaining gas free is a mutation? Yes, generally humans are lactose tolerant when they are born, so they can easily derive calories and nutrients from their mother's milk (which contains lactose). However, rather quickly as we age, we naturally lose our lactose tolerance and become lactose-intolerant. The current scientific theory behind how some of us are able to freely drink milk and remain lactose-tolerant into our old age is thus:

    • Lactose tolerance is naturally relatively high in certain populations that have access to large amounts of milk: whether from cows, goats, or sheep - as was seen in most of Europe, more nomadic tribes of Africa, as well as parts of Asia and the Middle East. In ancient times, milk was (and still is) a vast treasure trove of calories, nutrients, and vitamins that was very important to our scavenging and subsistence farming ancestors. Those who could digest milk (lactose tolerant or, as scientists call them, lactase persistent, because the digestive enzyme lactase remains active in them past their babyhood) were less likely to be hungry, vitamin deficient, and malnourished. Thus, they were more likely to survive to adulthood and more likely to reproduce, thus increasing the percentage of the populations with their gene for lactose tolerance or lactase-persistence.

    • On a genetic level, the mutation for lactose tolerance is a mere point mutation. The cytosine nucleotide which is considered normal, or wild-type; is switched with the thymine nucleotide.

• Abnormally high bone density:

  • Now, this is only abnormal because it is rare, but any mutation that can allow a person to walk unscathed (from a bones perspective at least) from a massive car crash, is quite the beneficial mutation indeed. Scientists discovered recently a mutation so far termed "LRP5". The LRP5 mutation stops the typical activity of a certain receptor that is involved in the activity of osteoporosis; a condition that you may have heard of concerning your grandmother or grandfather; or any older person with frequently breaking bones. People with the LRP5 mutation appear to be resistant to all kinds of bony injury or degeneration, whether from serious car crashes or the natural aging process. Overall this is considered a positive, or beneficial, mutation, that doctors are still trying to get to the root of, so they can hopefully use its processes to help others with weaker bones.

• Resistance to insulin resistance

  • We may all know by now that diabetes (type 2) is caused by insulin resistance. Also, type 2 diabetes is associated with certain risk factors and lifestyle choices, that can make it many times more likely to occur. Some of these risk factors include: obesity, high-carb diet, family history of diabetes, lack of exercise and so on. But what about people who have several of these risk factors, and yet do not have diabetes? Is it just raw luck or could they by chance be genetically pre-disposed to NOT get diabetes? Doctors believe they have discovered a gene that occurs in some people that makes them resistant to developing insulin resistance (diabetes). This gene is called SLC30A8 which is quite the mouthful, but the important things to know those who have the mutation are more than 50% less likely to get diabetes under the same circumstances as someone without that mutation. Pretty amazing!

More beneficial mutations examples

• Disease: Malaria

• Mutation: Hemoglobin C mutation

• Population: In certain populations of Sub-Saharan Africa where malaria was historically a major threat to wellbeing and survival (especially of children), there are higher rates of mutated hemoglobin - leading to hemoglobin C. Those with hemoglobin C are much less susceptible to malaria, thus this is a beneficial mutation in those populations.

• Disease: HIV

• Mutation: CCR5 (an HIV receptor)

• Population: In certain people with North European ancestry there has been found a mutated CCR5 gene, that leads to a complete inability for HIV to bind to their cells. These people are completely resistant to HIV, which is a very beneficial mutation.

• Disease: Heart disease (like heart attacks, stiff heart valves, clogged arteries, etc.)

• Mutation: Apolipoprotein A-I Milano (apolipoproteins help move cholesterol to and from our liver, clearing it from our blood)

• Population: In certain townships of Italy, some people have a mutated Apolipoprotein A-I. This mutation leads to more efficient clearing of cholesterol from the blood, reducing the risk of cardiovascular disease.

Beneficial mutations in animals and microorganisms

- Animal: Cows

- Mutation: Murray Gray coloring and increased fitness.

- Effects: Cows who randomly mutated this coloring were shown to have greater fertility and higher numbers of progeny.

- Organism: Bacteria

- Mutation: Antibiotic resistance.

- Effects: Bacteria can survive certain antibiotics when they develop resistance to them through mutations. This helps them to persist even when medications are applied.

- Animal: Fish

- Mutation: Antifreeze proteins (AFP).

- Effects: These mutations exist in fish that live in extremely cold climates. The mutation appears to be a duplication of the existing antifreeze gene, and it helps the fish to be hardier in the waters of the Arctic.