Interpreting the Dependence of Mutation Rates on Age and Time
Publication Date
January 13, 2016
Journal
PLOS Biology
Authors
Ziyue Gao, Minyoung J. Wyman, Guy Sella & Molly Przeworski
Volume
14
Issue
1
Pages
e1002355
DOI
https://dx.plos.org/10.1371/journal.pbio.1002355
Publisher URL
http://journals.plos.org/plosbiology/article?id=10.1371%2Fjournal.pbio.1002355
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/26761240
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711947
Europe PMC
http://europepmc.org/abstract/MED/26761240
Web of Science
000371882900021
Scopus
84956527440
Mendeley
http://www.mendeley.com/research/interpreting-dependence-mutation-rates-age-time
Events
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Mendeley | Further Information

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2627114"], "description"=>"<p>A visual summary of interpretation of existing observations based on our model and further predictions about germline and somatic mutations in humans.</p>", "links"=>[], "tags"=>["mutation", "dna", "cell divisions", "cell division rate"], "article_id"=>1637296, "categories"=>["Uncategorised"], "users"=>["Ziyue Gao", "Minyoung J. Wyman", "Guy Sella", "Molly Przeworski"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002355.g005", "stats"=>{"downloads"=>5, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_visual_summary_of_interpretation_of_existing_observations_based_on_our_model_and_further_predictions_about_germline_and_somatic_mutations_in_humans_/1637296", "title"=>"A visual summary of interpretation of existing observations based on our model and further predictions about germline and somatic mutations in humans.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-18 15:33:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/2627115", "https://ndownloader.figshare.com/files/2627116", "https://ndownloader.figshare.com/files/2627117", "https://ndownloader.figshare.com/files/2627118", "https://ndownloader.figshare.com/files/2627119"], "description"=>"<div><p>Mutations can originate from the chance misincorporation of nucleotides during DNA replication or from DNA lesions that arise between replication cycles and are not repaired correctly. We introduce a model that relates the source of mutations to their accumulation with cell divisions, providing a framework for understanding how mutation rates depend on sex, age, and cell division rate. We show that the accrual of mutations should track cell divisions not only when mutations are replicative in origin but also when they are non-replicative and repaired efficiently. One implication is that observations from diverse fields that to date have been interpreted as pointing to a replicative origin of most mutations could instead reflect the accumulation of mutations arising from endogenous reactions or exogenous mutagens. We further find that only mutations that arise from inefficiently repaired lesions will accrue according to absolute time; thus, unless life history traits co-vary, the phylogenetic “molecular clock” should not be expected to run steadily across species.</p></div>", "links"=>[], "tags"=>["mutation", "dna", "cell divisions", "cell division rate"], "article_id"=>1637297, "categories"=>["Uncategorised"], "users"=>["Ziyue Gao", "Minyoung J. Wyman", "Guy Sella", "Molly Przeworski"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1002355.s001", "https://dx.doi.org/10.1371/journal.pbio.1002355.s002", "https://dx.doi.org/10.1371/journal.pbio.1002355.s003", "https://dx.doi.org/10.1371/journal.pbio.1002355.s004", "https://dx.doi.org/10.1371/journal.pbio.1002355.s005"], "stats"=>{"downloads"=>4, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Interpreting_the_Dependence_of_Mutation_Rates_on_Age_and_Time_/1637297", "title"=>"Interpreting the Dependence of Mutation Rates on Age and Time", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2016-01-18 15:33:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/2627109"], "description"=>"<p>Explanation of terms: <b>Lesion</b>: chemically altered base; <b>noncoding lesion</b>: lesion that cannot pair properly with any regular DNA bases; <b>miscoding lesion</b>: lesion that pairs with regular DNA bases that differ from the original one; <b>correct repair</b>: repair that completely reverses the lesion to the original state; <b>incorrect repair</b>: repair that recognizes the mismatch caused by lesion but alters the undamaged base by mistake; <b>partial repair</b>: incomplete repair that leads to abasic sites or other base alterations; <b>replication error</b>: misincorporation of nucleotide in the newly synthesized strand despite intact template; <b>translesion DNA synthesis</b>: damage tolerance mechanism that allows the DNA replication to bypass lesions and is often mutagenic; <b>point mutation</b>: base pair substitution; <b>premutation</b>: a base pair at which a lesion is present on one strand and the base on the other strand is substituted, as a result of DNA synthesis from incorrect template information.</p>", "links"=>[], "tags"=>["mutation", "dna", "cell divisions", "cell division rate"], "article_id"=>1637291, "categories"=>["Uncategorised"], "users"=>["Ziyue Gao", "Minyoung J. Wyman", "Guy Sella", "Molly Przeworski"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002355.g001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_An_overview_of_the_mutagenesis_process_which_involves_DNA_damage_repair_and_replication_adapted_from_5_/1637291", "title"=>"An overview of the mutagenesis process, which involves DNA damage, repair, and replication (adapted from [5]).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-18 15:33:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/2627111"], "description"=>"<p>(A) An illustration of the increase in the number of germ cell divisions with age in humans. For legibility, the plot is not exactly to scale and the final four cell divisions in males needed to complete spermatogenesis are not shown. The origin is the time of fertilization, and SD, B, P, and G are the times of sexual differentiation, birth, onset of puberty, and reproduction (i.e., generation time), respectively. (B) The increase in the number of mutations due to replication errors with sex and age. (C) The ratio of mutations that occurred in the male versus the female germline (the “male bias”) as a function of increasing parental age.</p>", "links"=>[], "tags"=>["mutation", "dna", "cell divisions", "cell division rate"], "article_id"=>1637293, "categories"=>["Uncategorised"], "users"=>["Ziyue Gao", "Minyoung J. Wyman", "Guy Sella", "Molly Przeworski"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002355.g002", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_accumulation_of_replication_driven_mutations_with_sex_and_age_/1637293", "title"=>"The accumulation of replication-driven mutations with sex and age.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-18 15:33:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/2627112"], "description"=>"<p>The sex-averaged mutation rate per generation (solid purple line) increases with the generation time (assumed to be the same for males and females). Depending on the age of puberty (<i>P</i>), generation time (<i>G</i>), and the per cell division mutation rates, a linear fit to the number of mutations after puberty (dotted purple line) could have a zero, positive, or negative intercept at age zero, and the slope of this linear fit represents the yearly mutation rate after puberty. The slope of the green line represents the average yearly mutation rate prior to puberty. The effect of <i>G</i> on the overall average yearly mutation rate (<i>m</i><sub>R,y</sub>) depends on the relative values of the two slopes, which is equivalent to the sign of the intercept of dotted purple line at age zero: (A) If the intercept is zero, the dotted purple and green lines coincide, and the yearly mutation rates before and after puberty are equal, so the <i>G</i> does not affect <i>m</i><sub>R,y</sub>. (B) If the intercept is positive, the yearly mutation rate after puberty is smaller than that before puberty, so <i>m</i><sub>R,y</sub> decreases with generation time. (C) If the intercept is negative, the yearly mutation rate after puberty is greater than that before puberty, so <i>m</i><sub>R,y</sub> increases with generation time.</p>", "links"=>[], "tags"=>["mutation", "dna", "cell divisions", "cell division rate"], "article_id"=>1637294, "categories"=>["Uncategorised"], "users"=>["Ziyue Gao", "Minyoung J. Wyman", "Guy Sella", "Molly Przeworski"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002355.g003", "stats"=>{"downloads"=>2, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effect_of_the_generation_time_on_the_sex_averaged_yearly_rate_of_replication_driven_mutations_/1637294", "title"=>"The effect of the generation time on the sex-averaged yearly rate of replication-driven mutations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-18 15:33:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/2627113"], "description"=>"<p>(A) The DNA dynamics before and after cell division. The upper panel shows the DNA states prior to the next cell division, and the lower panel shows the DNA states of the daughter cells after cell division. (B) The per cell division mutation rate increases with the time between two consecutive cell divisions and reaches an asymptote when the cell divides sufficiently slowly. (C) The rate at which non-replicative mutations accumulate per unit time increases with the cell division rate.</p>", "links"=>[], "tags"=>["mutation", "dna", "cell divisions", "cell division rate"], "article_id"=>1637295, "categories"=>["Uncategorised"], "users"=>["Ziyue Gao", "Minyoung J. Wyman", "Guy Sella", "Molly Przeworski"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002355.g004", "stats"=>{"downloads"=>2, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_basic_model_for_non_replicative_mutations_/1637295", "title"=>"The basic model for non-replicative mutations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-18 15:33:30"}

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Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
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