International Business Department           Liu Bojia           August 14, 2023

  According to the theory of natural selection, if a genetic variation produces a phenotype that favors an individual's survival in the current environment, then that genetic information has a better chance of being retained and passed on to the next generation, and vice versa. Of course, this theory does not represent the entire explanation for evolution, and many modern discoveries continue to refine and iterate on it.

  For humans, the APOE gene is a mind-boggling example. This gene is responsible for encoding Apolipoprotein E, which is primarily involved in the conversion and metabolism of lipoproteins, and also assists in the transport of cholesterol through the bloodstream. There are three main APOE mutations in human genetics, with the ε type 4 mutation (APOE4) being significantly associated with the risk of Alzheimer's Disease (AD) and cardiovascular disease, with having one APOE4 increasing the risk of AD by 2-fold, and with two APOE4s, the risk rises by 11-12-fold.

However, about 20% of the population will carry at least one APOE4, which is tantamount to exposing yourself to a great risk of disease and death. It's even more counterintuitive why a gene that damages one's health hasn't been eliminated and continues to be perpetuated.

  When we can't find the answer in our current social environment, looking back at human evolution can actually be illuminating. Benjamin Trumble, a professor of human evolution at Arizona State University, has been focusing on human communities that have not been impacted by industrialization, many of whom still perform hunting and gathering lifestyles that better reflect historical scenarios in human evolution.

  "Close to 99% of human history has been spent executing a hunter-farmer life, and it's the current life that's really 'weird' in that it's so far removed from past evolutionary circumstances." Prof. Trumble said. In their latest paper in Science-Progress, he and colleagues look at Tsimané populations in the Brazilian Amazon, who still engage in a lifestyle of hunting, gathering and farming.

Over 20 years, the team collected data on 795 women in the population, including investigating their reproductive history and testing the status of APOE4 in the gene. On average, Tsimané women will have nine children in their lifetime, but when APOE4 is brought into the analysis it is found that women who carry one APOE4 gene will have an average of 9.5 children, while having two APOE4 genes will result in an additional two children over women who do not have the APOE4 gene.

  In addition to the overall number of children, APOE4 can alter the fertility of Tsimané women, such as making them slightly heavier, conceiving offspring a year earlier than women without the APOE4 gene, and having shorter intervals between pregnancies. And APOE4 confers better immunity in children, enhancing their ability to cope with parasitic infections.

  It also means that these women have more energy to spend on growing their bodies and accomplishing childbearing. It may be difficult to understand for people who have long been accustomed to life in urbanized, convenient societies, but under the hunting-farming life, population is a guarantee for the continuation of a community, and Dr. Tábita Hünemeier, a geneticist at the University of São Paulo, points out that, "The advantage of fertility enhancement is so great that natural selection has preserved the APOE4 gene. " And the early benefit of APOE4, which allows it to continue to be passed on to the next generation, doesn't conflict with the late disadvantage - after all, AD and cardiovascular disease both occur at older ages, beyond the window in which natural selection can intervene.

  The researchers note that they did not find a relationship between APOE4 and fertility in urban populations; one possibility is that urban populations rarely experience parasitic infections, so the growth advantage it confers is less pronounced, and also that birth control masks some of this effect.

  It also suggests that a gene that now appears to be pathogenic may well have played no small role in the evolution of human history. Understanding the origins and changes in these genes may allow us to better cope with disease. People like those in Tsimané have a lower risk of AD and cardiovascular disease even with the AOPE4 gene, and mimicking some of their lifestyles might help susceptible populations in the city to better prevent the onset of disease.