Welham Girls' School

Why do disease genes persist in the human gene pool?

Shouldn’t evolution by natural selection slowly eliminate harmful genes by the theory of survival of the fittest stated by Charles Darwin in 1869. Persistence of these genes can be understood by the concept of Heterozygote Advantage. Heterozygote Advantage means having one good gene and one disease gene in some situations is better than having two good or two bad genes. Heritable traits are passed on through genes. We have 40 million genes and get two copies of each gene, one from each biological parent. A person is homozygous when both genes are similar or heterozygous when the genes are different.

In the well know genetic disease; Sickle cell anemia, a person can have the disease only if both disease genes are present. If a person has one disease gene, then that person is a carrier of the disease, but does not have it. In Sickle cell anemia the red blood cells become crescents instead of the normal oval shape and prevent enough oxygen to be delivered to various body organs by blocking the passage of arteries. These diseased individuals would die at a young age. What is most perplexing about this disease is that it surprisingly common in some populations. Geographical areas with high sickle cell disease also have high incidence of malaria, a deadly disease caused by a mosquito bite which injects a parasite that destroys the RBCs. Heterozygote individuals with only one copy of sickle cell gene have enough normal red blood cells but also have some sickle cells. These sickle cells in blood offer resistance to the malarial parasite. So, although as a carrier you have an equal chance of being bitten by the mosquito but a much lower chance of getting malaria and dying from it. Therefore, areas where malaria is more prevalent, it tips the selective balance in favor of sickle cell heterozygote individuals. The evolutionary tradeoff is, that protection from malaria comes at the cost of more sickle cell disease within the population.

Similarly in cystic fibrosis, the body produces thick mucus in various organs which further leads to death. However, heterozygote carriers of this disease have protection against cholera a disease that causes severe diarrhea. The bacteria causing cholera binds to the cells of the intestines which pour the water and salt out. In cystic fibrosis there is a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which secretes water and salt from tissue cells. Therefore, the heterozygote carriers of the CFTR mutation will not have cystic fibrosis and will secrete less fluids if infected by cholera ,because cholera was fairly common in past, natural selection favored cystic fibrosis carriers.

 

To sum up, in both sickle cell and cystic fibrosis the disease-causing mutation has beneficial effects not for people who have two faulty genes and get the fatal disease, but for people who have only one faulty gene copy and are more likely to survive and pass on their genes including the disease gene. So, we learn that the currency that evolution deals with is reproduction not health. This concept challenges the notion that our body should have gotten better over time. There are many other known and perhaps yet to be discovered mysteries that further genetic studies will unravel. Hopefully our deep insights into these processes of evolutionary medicine may help us in finding ways to improve human health.