Protective HIV-Resistant Gene Mutation Linked To Increased All-Cause Mortality
In a paper published in Nature last week, Xinzhu Wei and Rasmus Nielsen reiterated the serious implications involved in the emerging theory of selecting for certain mutations within the human fetal genome, adding that certain mutations that seem to come with positive effects, can also confer unexpected negative traits upon their bearer.
Using genotyping information and death registry data from over 400,000 Englishmen and women, Wei demonstrated in his paper that individuals who carry two copies of the Δ32 mutation of the CCR5 gene (which protects against HIV infection in Europeans) have a 21% increase in mortality rate.
Wei and Nielsen found a 21% increase in all-cause mortality, (death from all causes) and a 20% reduction in the chance to live to 76 years of age.
One Small Step for Man
In 2018, Chinese scientist Jiankui He announced that he had used CRISPR to edit the CCR5 gene in human embryos which later produced two children. This was unsanctioned by international practice organizations, and much was made about the first small step for human gene editing.
Along with the new paper by Wei and Nielsen, previous studies have shown the HIV resistant Δ32 mutation leads to increased risk for influenza and other infectious diseases. The practice of such gene-modification is unsanctioned for the exact reason that it is difficult to ascertain whether the positive effects associated with this or that mutation are without risk of genetic backlashes.
A perfect example of this is the well-known disease prevalent within black communities called sickle-cell anaemia. The sickle cell hemoglobin gene confers a power resistance to malaria, and is only found within malaria-endemic regions of the world, hence it’s distribution in black communities.
It protects against severe malarial-anaemia, high-density parasitaemia, and all-cause mortality between the ages of 2 and 16. However, the increased risk for mortality that comes with the sickle-cell hemoglobin gene is also very well documented.
This give-and-take is common within evolution, and seems to be the case with the Δ32 mutation of the CCR5 gene. Again, here is a gene which protects a given population from a fatal disease, yet at the same time appears to confer a genetic susceptibility as well.
An Evolutionary Puzzle
The give-and-take nature of certain studied mutations makes for good a case study for examining genetic mechanisms and models for mortality at large.
Death itself, and several causes of death have been theorized as being a give-and-take genetic relationship. If one were to ask why hasn’t natural selection evolved a species capable of immortality, the general consensus among scholars would be that it would’ve been evolutionary inefficient to do so.
The model is simple and elegant.
Two mechanism can trigger an individual to die, intrinsic force and extrinsic force. The natural world is an extraordinarily dangerous place, and in order to gather food, find a mate, and propagate the species, early homo sapiens had to contend with animal attacks, starvation, inter-tribal warfare, natural hazards, and accidents.
As an organic lifeform ages, the chance that extrinsic forces will inevitably strike it down becomes higher and higher, eventually reaching a probability percentage of indefinite. As such, expending the evolutionary energy to create a lifeform entirely free from the risk of death from intrinsic forces becomes inefficient and pointless, since extrinsic harm will eventually inflict mortal damage.
In 1941 evolutionary biologist J.B.S. Haldane considered the possibility that rates of natural selection in aged individuals declined indefinitely, and that this could be the cause for the relatively high prevalence of the dominant gene allele which causes Huntington’s disease in humans.
He theorized that since Huntington's typically only affects people beyond age 30, such a disease would not have been efficiently eliminated by selection in ancestral, pre-modern populations because most people would already have died before they could experience this late-onset disease. Thus, the disease would not have been "seen" by, or subject to, natural selection.
High prevalence of sickle-cell haemoglobin levels in human fetuses are shown in the study mentioned above to be a sign of significant reduction in mortality between the ages of 2-16. Homo sapiens are perfectly capable of reproducing by age 16, and so you have a genetic adaptation to resist the spread of a lethal disease, (malaria) but that, as the study shows, begins to intrinsically damage the body later in life, between age 40-48 in males.
Because of this complicated give-and-take relationship between human culture, the natural environment, and the evolutionary drivers which have allowed us to survive, any attempt to alter that picture must be done with extreme caution, as eloquently demonstrated in Wei and Nielsen’s study.