Evolutionary genetics and acclimatization in nephrology

Abstract

Evolutionary processes, including mutation, migration and natural selection, have influenced the prevalence and distribution of various disorders in humans. However, despite a few well-known examples, such as the APOL1 variants — which have undergone positive genetic selection for their ability to confer resistance to Trypanosoma brucei infection but confer a higher risk of chronic kidney disease — little is known about the effects of evolutionary processes that have shaped genetic variation on kidney disease. An understanding of basic concepts in evolutionary genetics provides an opportunity to consider how findings from ancient and archaic genomes could inform our knowledge of evolution and provide insights into how population migration and genetic admixture have shaped the current distribution and landscape of human kidney-associated diseases. Differences in exposures to infectious agents, environmental toxins, dietary components and climate also have the potential to influence the evolutionary genetics of kidneys. Of note, selective pressure on loci associated with kidney disease is often from non-kidney diseases, and thus it is important to understand how the link between genome-wide selected loci and kidney disease occurs in relation to secondary nephropathies. Here, the authors provide an overview of the evolutionary processes that have implications for our understanding of kidney disease development and progression. They describe data derived from studies of ancient and archaic genomes and how population migration and genetic admixture have shaped the current landscape of human kidney-associated diseases, as well as the potential impact of environmental influences on evolutionary genetics and the adaptation of kidneys. Kidney diseases that have an age of onset after the reproductive age (that is, most forms of chronic kidney disease) are unlikely to act as agents of natural selection for the elimination of disease-causing alleles because those alleles are successfully transmitted to successive generations. Several loci under natural selection owing to the protection they provide against infectious agents (for example, Trypanosoma brucei and Plasmodium falciparum) have an effect on the risk of kidney disease (APOL1-associated chronic kidney disease and sickle cell nephropathy, respectively). Loci that are under natural selection and that increase the risk of disorders that damage the kidney (such as diabetes mellitus and hypertension) may contribute to the risk of secondary nephropathies. Only a handful of genetic loci identified by genome-wide association studies as being associated with complex kidney diseases show evidence of natural selection in primates; however, many more of these loci show evidence of natural selection in human populations, suggesting that most selective events at kidney-associated loci occurred relatively recently in the evolution of the human species. Kidney diseases that have an age of onset after the reproductive age (that is, most forms of chronic kidney disease) are unlikely to act as agents of natural selection for the elimination of disease-causing alleles because those alleles are successfully transmitted to successive generations. Several loci under natural selection owing to the protection they provide against infectious agents (for example, Trypanosoma brucei and Plasmodium falciparum) have an effect on the risk of kidney disease (APOL1-associated chronic kidney disease and sickle cell nephropathy, respectively). Loci that are under natural selection and that increase the risk of disorders that damage the kidney (such as diabetes mellitus and hypertension) may contribute to the risk of secondary nephropathies. Only a handful of genetic loci identified by genome-wide association studies as being associated with complex kidney diseases show evidence of natural selection in primates; however, many more of these loci show evidence of natural selection in human populations, suggesting that most selective events at kidney-associated loci occurred relatively recently in the evolution of the human species.