EVOLUTIONARY MEDICAL GENOMICS

«Nothing in biomedicine makes sense except in the light of evolution». From this point of view, genetics of predispositions hasto answer two basic questions: 1. Is the natural genetic polymorphism identified with modern genomics proved to be the result of neutral evolution or whether it is an aggravated genetic (mutation) load determining the susceptibility to common diseases, which inexplicably has not been culled bythe natural selection well-timed? 2. Are effects of different predisposing alleles synergistic or at least additive when combined in a single genotype, or they are mutually neutralized? Evolutionary and population arguments help to understand that the «genetics of predispositions» studies natural balanced genetic polymorphism, i.e. not newly formed alterations of genes (mutations), but alleles passed natural selection and fixed in human populations. Not anomalies, not pathological or pathogenic variants of the genome are investigated, but infinite number of its natural, «normal»variants. Thus the answers on the above two questions are: 1. Evolutionary medical genomics testifies that the vast majority of polymorphic variants of genes (alleles) that are observed in the genomes of modern human populations are selectively neutral. 2. In many cases, the effects of various predisposing alleles are mutually neutralized through the mechanisms of opposite (antagonistic) pleiotropy and homeostasis.