How important is DNA replication for mutagenesis?
Huttley, Gavin Austin; Jakobsen, I; Easteal, Simon
Description
Rates of mutation and substitution in mammals are generally greater in the germ lines of males. This is usually explained as resulting from the larger number of germ cell divisions during spermatogenesis compared with oogenesis, with the assumption made that mutations occur primarily during DNA replication. However, the rate of cell division is not the only difference between male and female germ lines, and mechanisms are known that can give rise to mutations independently of DNA replication....[Show more]
dc.contributor.author | Huttley, Gavin Austin | |
---|---|---|
dc.contributor.author | Jakobsen, I | |
dc.contributor.author | Easteal, Simon | |
dc.date.accessioned | 2015-12-13T23:15:44Z | |
dc.identifier.issn | 0737-4038 | |
dc.identifier.uri | http://hdl.handle.net/1885/89036 | |
dc.description.abstract | Rates of mutation and substitution in mammals are generally greater in the germ lines of males. This is usually explained as resulting from the larger number of germ cell divisions during spermatogenesis compared with oogenesis, with the assumption made that mutations occur primarily during DNA replication. However, the rate of cell division is not the only difference between male and female germ lines, and mechanisms are known that can give rise to mutations independently of DNA replication. We investigate the possibility that there are other causes of male-biased mutation. First, we show that patterns of variation at ~5,200 short tandem repeat (STR) loci indicate a higher mutation rate in males. We estimate a ratio of male-to- female mutation rates of ~1.9. This is significantly greater than 1 and supports a greater rate of mutation in males, affecting the evolution of these loci. Second, we show that there are chromosome-specific patterns of nucleotide and dinucleotide composition in mammals that have been shaped by mutation at CpG dinucleotides. Comparable patterns occur in birds. In mammals, male germ lines are more methylated than female germ lines, and these patterns indicate that differential methylation has played a role in male-biased vertebrate evolution. However, estimates of male mutation bias obtained from both classes of mutation are substantially lower than estimates of cell division bias from anatomical data. This discrepancy, along with published data indicating slipped-strand mispairing arising at STR loci in nonreplicating DNA, suggests that a substantial percentage of mutation may occur in nonreplicating DNA. | |
dc.publisher | Society for Molecular Biology Evolution | |
dc.source | Molecular Biology and Evolution | |
dc.subject | Keywords: article; DNA replication; gene locus; gene mutation; germ cell; human; mutagenesis; nonhuman; tandem repeat; Animals; Cell Division; DNA Methylation; DNA Replication; Female; Homozygote; Humans; Male; Mice; Minisatellite Repeats; Models, Genetic; Mutagene CpG methylation; DNA replication; Male-biased mutation; Mammals; Mutation; Short tandem repeat loci | |
dc.title | How important is DNA replication for mutagenesis? | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.description.refereed | Yes | |
local.identifier.citationvolume | 17 | |
dc.date.issued | 2000 | |
local.identifier.absfor | 110706 - Immunogenetics (incl. Genetic Immunology) | |
local.identifier.ariespublication | MigratedxPub18938 | |
local.type.status | Published Version | |
local.contributor.affiliation | Huttley, Gavin Austin, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Jakobsen, I, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Easteal, Simon, College of Medicine, Biology and Environment, ANU | |
local.description.embargo | 2037-12-31 | |
local.bibliographicCitation.startpage | 929 | |
local.bibliographicCitation.lastpage | 937 | |
dc.date.updated | 2015-12-12T08:44:56Z | |
local.identifier.scopusID | 2-s2.0-0034076857 | |
Collections | ANU Research Publications |
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