Selective Constraints on Human Disease Mutations and Polymorphisms.

HERNÁN DOPAZO

Handbook of Human Molecular Evolution

John Wiley & Sons, Ltd. UK.

Año: 2008; p. 1546 - 1564

Natural selection rejects with variable strength, mutations reducing the individual’s capability to survive and reproduce. Evolutionary theory predicts that mutations producing disease will be under strong selective constraints. Selective strength at the codon level will determine if mutation frequency will increase, decrease or change randomly during evolution. This strength finally serves in the prediction of nonsynonymous single nucleotide polymorphisms (nsSNPs) producing disease in humans. By using comparative genomics data and maximum likelihood phylogenetics approaches we demonstrate that mutations on residues showing low rates of evolution are significantly associated to disease and not to human genetic polymorphisms.