Can “deleterious genes variants” be beneficial? Antagonistic pleiotropy on the example of the ApoE gene

Antagonistic pleiotropy is a phenomenon where one gene has both beneficial and detrimental effects. Apolipoprotein E is of particular interest due to its pleiotropic effects. It is encoded by the ApoE gene, which has three variants: ApoE2, ApoE3, and ApoE4. The ApoE4 allele is a classic example of antagonistic pleiotropy. On the one hand, its presence increases the risk of diseases related to cholesterol metabolism, such as ischemic heart disease and Alzheimer’s disease. On the other hand, ApoE4 can increase fertility, indicating potential reproductive benefits. This article provides an overview of the established detrimental effects of the ApoE4 allele and a comprehensive analysis of eight studies (1996–2023) on the effects of APOE polymorphism on fertility. Antagonistic pleiotropy plays a crucial role in the evolution of the human genome, explaining why some deleterious gene variants persist in populations. Understanding these mechanisms is key to explaining the complexity of human evolution and health.