View Full Document

Rate, molecular spectrum, and consequences of human mutation



View the full content.
View Full Document
View Full Document

5 views

Unformatted text preview:

INAUGURAL ARTICLE Rate molecular spectrum and consequences of human mutation Michael Lynch1 Department of Biology Indiana University Bloomington IN 47405 This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected in 2009 Although mutation provides the fuel for phenotypic evolution it also imposes a substantial burden on tness through the production of predominantly deleterious alleles a matter of concern from a human health perspective Here recently established databases on de novo mutations for monogenic disorders are used to estimate the rate and molecular spectrum of spontaneously arising mutations and to derive a number of inferences with respect to eukaryotic genome evolution Although the human per generation mutation rate is exceptionally high on a per cell division basis the human germline mutation rate is lower than that recorded for any other species Comparison with data from other species demonstrates a universal mutational bias toward A T composition and leads to the hypothesis that genome wide nucleotide composition generally evolves to the point at which the power of selection in favor of G C is approximately balanced by the power of random genetic drift such that variation in equilibrium genome wide nucleotide composition is largely de ned by variation in mutation biases Quanti cation of the hazards associated with introns reveals that mutations at key splicesite residues are a major source of human mortality Finally a consideration of the long term consequences of current human behavior for deleterious mutation accumulation leads to the conclusion that a substantial reduction in human tness can be expected over the next few centuries in industrialized societies unless novel means of genetic intervention are developed base substitutions human genetic disorders mutational spectrum D introns mutation rate espite its central signi cance to matters of health and phenotypic evolution many



Access the best Study Guides, Lecture Notes and Practice Exams

Loading Unlocking...
Login

Join to view Rate, molecular spectrum, and consequences of human mutation and access 3M+ class-specific study document.

or
We will never post anything without your permission.
Don't have an account?
Sign Up

Join to view Rate, molecular spectrum, and consequences of human mutation and access 3M+ class-specific study document.

or

By creating an account you agree to our Privacy Policy and Terms Of Use

Already a member?