The Rate of Human Germline Mutations—Variable Factor of Evolution and Diseases

The emergence of genetic diseases and evolutionary processes are associated with the flow of genetic information from one generation to another, in which genetic information carried by gametes can be changed by the appearance of de novo germline mutations. The rate of germline mutations determines the rate of evolution and the incidence of heritable disorders. Despite the great theoretical and practical importance, the problem of establishing mutation rates and their dependence on different factors remains scarcely studied, and the mutation rate values obtained by different methods vary considerably. The review discusses different ways of estimating the rate of these mutations and makes an attempt to explain the reasons for discrepancies in the data obtained. Three levels of the mutation formation are considered: (1) mutations that are formed during the development of a given individual during gametogenesis (basic mutations); (2) mutations transmitted to offspring and determining differences in the genomes of consecutive generations (parents and offspring), which include basic mutations and possible changes resulting from complex processes of sperm transfer to oocyte, fertilization, and subsequent events that lead to only one viable offspring of hundreds of millions spermatozoa and oocytes; (3) mutations which are formed at level 2, fixed in evolution, and determine evolutionary processes and differences between genomes, in particular, of hominoids, hominids, and hominins.