Age-related somatic mutation burden in human tissues

Abstract

The genome of multicellular organisms carries the hereditary information necessary for the development of all organs and tissues and to maintain function in adulthood. To ensure the genetic stability of the species, genomes are protected against changes in sequence information. However, genomes are not static. De novo mutations in germline cells are passed on to offspring and generate the variation needed in evolution. Moreover, postzygotic mutations occur in all somatic cells during development and aging. These somatic mutations remain limited to the individual, generating tissues that are genome mosaics. Insight into such mutations and their consequences has been limited due to their extremely low abundance, with most mutations unique for each cell. Recent advances in sequencing, including whole genome sequencing at the single-cell level, have now led to the first insights into somatic mutation burdens in human tissues. Here, we will first briefly describe the latest methodology for somatic mutation analysis, then review our current knowledge of somatic mutation burden in human tissues and, finally, briefly discuss the possible functional impact of somatic mutations on the aging process and age-related diseases, including cancer and diseases other than cancer.

Keywords: aging; clonal amplification; mutation burden; single-cell sequencing; somatic mutation.