Problems with studying directional natural selection in humans

• Published in: Vavilovskiĭ zhurnal genetiki i selekt͡s︡ii Vol. 27; no. 6; pp. 684 - 693
• Main Author: Mikhailova, S. V.
• Format: Journal Article
• Language: English
• Published: Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders 01-01-2023
• Subjects: adaptation; fertility; genome-wide association study; homo sapiens; natural selection; polygenic index
• ISSN: 2500-3259; 2500-0462; 2500-3259
• DOI: 10.18699/VJGB-23-79

The review describes the main methods for assessing directional selection in human populations. These include bioinformatic analysis of DNA sequences via detection of linkage disequilibrium and of deviations from the random distribution of frequencies of genetic variants, demographic and anthropometric studies based on a search for a correlation between fertility and phenotypic traits, genome-wide association studies on fertility along with genetic loci and polygenic risk scores, and a comparison of allele frequencies between generations (in modern samples and in those obtained from burials). Each approach has its limitations and is applicable to different periods in the evolution of Homo sapiens. The main source of error in such studies is thought to be sample stratification, the small number of studies on nonwhite populations, the impossibility of a complete comparison of the associations found and functionally significant causative variants, and the difficulty with taking into account all nongenetic determinants of fertility in contemporary populations. The results obtained by various methods indicate that the direction of human adaptation to new food products has not changed during evolution since the Neolithic; many variants of immunity genes associated with inflammatory and autoimmune diseases in modern populations have undergone positive selection over the past 2–3 thousand years owing to the spread of bacterial and viral infections. For some genetic variants and polygenic traits, an alteration of the direction of natural selection in Europe has been documented, e. g., for those associated with an immune response and cognitive abilities. Examination of the correlation between fertility and educational attainment yields conflicting results. In modern populations, to a greater extent than previously, there is selection for variants of genes responsible for social adaptation and behavioral phenotypes. In particular, several articles have shown a positive correlation of fertility with polygenic risk scores of attention deficit/hyperactivity disorder.