Elevated germline mutation rate in teenage fathers.

Bibliographic Collection: 
Publication Type: Journal Article
Authors: Forster, Peter; Hohoff, Carsten; Dunkelmann, Bettina; Schürenkamp, Marianne; Pfeiffer, Heidi; Neuhuber, Franz; Brinkmann, Bernd
Year of Publication: 2015
Journal: Proc Biol Sci
Volume: 282
Issue: 1803
Pagination: 20142898
Date Published: 2015 Mar 22
Publication Language: eng
ISSN: 1471-2954
Keywords: Adolescent, Adult, Africa, Age Factors, Aged, Child, Europe, Fathers, Female, Germ-Line Mutation, Humans, Male, Microsatellite Repeats, Middle Aged, Middle East, Mothers, Sex Factors, Spermatogonia, Spermatozoa

Men age and die, while cells in their germline are programmed to be immortal. To elucidate how germ cells maintain viable DNA despite increasing parental age, we analysed DNA from 24 097 parents and their children, from Europe, the Middle East and Africa. We chose repetitive microsatellite DNA that mutates (unlike point mutations) only as a result of cellular replication, providing us with a natural 'cell-cycle counter'. We observe, as expected, that the overall mutation rate for fathers is seven times higher than for mothers. Also as expected, mothers have a low and lifelong constant DNA mutation rate. Surprisingly, however, we discover that (i) teenage fathers already set out from a much higher mutation rate than teenage mothers (potentially equivalent to 77-196 male germline cell divisions by puberty); and (ii) ageing men maintain sperm DNA quality similar to that of teenagers, presumably by using fresh batches of stem cells known as 'A-dark spermatogonia'.

DOI: 10.1098/rspb.2014.2898
Alternate Journal: Proc. Biol. Sci.