Numbers of mutations within multicellular bodies: why it matters

Abstract

Multicellular organisms often start life as a single cell. Subsequent cell division builds the body. Each mutational event during those developmental cell divisions carries forward to all descendant cells. The overall number of mutant cells in the body follows the Luria-Delbruck process. This article first reviews the basic quantitative principles by which one can understand the likely number of mutant cells and the variation in mutational burden between individuals. A new Frechet distribution approximation greatly simplifies calculation of likelihoods and intuitive understanding of process. The second part of the article highlights consequences of somatic mutational mosaicism for understanding diseases such as cancer, neurodegeneration, and atherosclerosis.