The most interesting human mutations in the world!

Human mutations are some changes in the human genotype (DNA) that may be manifested as phenotypic changes. Some of these are beneficial. Some are lethal! Let' talk about some of the most interesting genetic mutations in human being!

Stephen Crohn: The first man on earth to be resistant to HIV, also known as "The man who can't catch AIDS"

Before telling the exact details of the mutation, and how Crohn became resistant to HIV. I want to tell you some very basic concepts of how HIV infects humans and ultimately causes death almost 10–15 years after exposure.

HIV infects our white blood cells. Specifically, a type of white blood cell called Helper T-cell CD4. Firstly, the receptor on HIV called gp120 reacts to a receptor on the WBC called CD4 protein. After this interaction, the virus exposes another part of its GP120 molecule that interacts with another protein on the WBC called CCR5. CCR5 anchors the virus on the cell membrane and helps in the fusion of both membranes together. HIV enters the cell, infects it, replicate itself, and ultimately the cell rupture releasing new viral particles to infect other cells till it suppresses our immune system!

It turns out that Crohn was missing the gene that was responsible for CCR5 protein! As we know that each protein is produced is coded by a specific gene in our DNA. This lucky guy didn’t have that gene and, thus, this protein which was used by HIV was missing from him! This is how CCR5 looks like

Another very interesting mutation is called the Duffy antigen mutation which makes people resistant to malaria!

Malaria is a parasite that infects our RBCs leading to severe hemolytic anemia. It is a very bad parasite and, unfortunately, very common, infecting 228 million people in 2019!

There is a receptor called Duffy antigen/chemokine receptor (DARC.) It is believed that this receptor plays role in immunity. This receptor is used by Malaria Vivax to enter the RBC. Some people are Duffy antigen-negative and, luckily, resistant to malaria vivax!

FAVA BEAN ANEMIA PEOPLE ARE ALSO RESISTANT TO MALARIA!

This mutation is called G6DP. Without going into detail, G6PD is responsible for generating a molecule called NADPH. NADPH is responsible for creating an anti-oxidant called glutathione. When you eat beans, you introduce to your blood a lot of substances that can cause oxidation of your Hemoglobin molecule inside RBCs. This is bad for RBCs. Glutathione is responsible for defending against this oxidative stress. When you are deficient in G6PD, you are deficient in glutathione and, thus, can’t defend yourself against oxidants. That’s why you can’t eat beans.

Malaria falciparum can’t withstand this oxidative stress inside your RBCs, thus, they die and don’t infect you! It is believed that this mechanism evolved to protect people from infection with malaria in Africa!

Some people can’t drink alcohol due to a mutation in their DNA!

It is called aldehyde dehydrogenase (ALDH) deficiency. Alcohol, which you drink, is called, scientifically, ethanol. Ethanol should be metabolized in our bodies. The pathway for its metabolism consist of 2 steps as shown below:

I want you to imagine that some people don’t have the ALDH. It means that whenever they drink ethanol, they will have a HUGE amount of acetaldehyde that can’t be metabolized. Unfortunately, this substance is toxic to our liver (This is why alcohol causes liver cirrhosis)

The build-up of acetaldehyde causes blood vessels to dilate and the face to turn red - the so-called “Asian flush syndrome”. Literally, when any of these people drink alcohol, their face turns into dark red and other symptoms can be manifested such as dermatitis, urticaria, nausea, and vomiting.

I hope you enjoyed this nerdy stuff!