title: Elevated germline mutation rate in teenage fathers.
abstract: 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'.
authors.affiliation: Institute for Forensic Genetics, Münster 48161, Germany Murray Edwards College, University of Cambridge, Cambridge CB3 0DF, UK pf223@cam.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: Forster
authors.affiliation: Institute for Forensic Genetics, Münster 48161, Germany hohoff@ifg-ms.de.
authors.forename: Carsten
authors.initials: C
authors.lastname: Hohoff
authors.affiliation: Institute of Legal Medicine, University of Salzburg, Ignaz-Harrer-Strasse 79, Salzburg 5020, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Dunkelmann
authors.affiliation: Institute of Legal Medicine, University of Münster, Münster 48149, Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: Schürenkamp
authors.affiliation: Institute of Legal Medicine, University of Münster, Münster 48149, Germany.
authors.forename: Heidi
authors.initials: H
authors.lastname: Pfeiffer
authors.affiliation: Institute of Legal Medicine, University of Salzburg, Ignaz-Harrer-Strasse 79, Salzburg 5020, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Neuhuber
authors.affiliation: Institute for Forensic Genetics, Münster 48161, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Brinkmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000349:Africa; D000367:Age Factors; D000368:Aged; D002648:Child; D005060:Europe; D005220:Fathers; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D008877:Middle East; D009035:Mothers; D012737:Sex Factors; D013093:Spermatogonia / Q000166:cytology; D013094:Spermatozoa / Q000166:cytology
keywords: ageing; immortality; molecular clock; oogenesis; spermatogenesis; stem cell