De Novo Mutation Rate Estimation in Wolves of Known Pedigree
De Novo Mutation Rate Estimation in Wolves of Known Pedigree
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DOI：
10.1093/molbev/msz159
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发表时间：
2019-11-01
影响因子：
10.7
通讯作者：
Novembre, John
中科院分区：
文献类型：
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作者：
Koch, Evan M.;Schweizer, Rena M.;Novembre, John
了解突变率对于校准以年为单位的人口历史的群体遗传学模型至关重要。然而，由于需要识别极其罕见的事件，估计突变率仍然具有挑战性。我们通过鉴定七只狼的谱系中的新生突变来估计狼的核突变率。推定的从头突变是通过全基因组测序发现的，并通过父母和后代的桑格测序得到验证。使用严格的过滤器和对剩余可观察基因组中假阴性率的估计，我们获得了类似于每代每个碱基对 4.5 x 10(-9) 的估计，并提供了 2.6 x 10(-9) 和 7.1 x 10(-9) 之间的保守界限。尽管我们的估计与最近对古代 DNA 的突变率估计（4.0 x 10(-9) 和 3.0-4.5 x 10(-9)）一致，但它表明可能的范围更广。我们还研究了我们的比率和伴随的间隔对犬科动物人口历史上几个关键事件的年代的影响。例如，将我们的全部比率应用于狗和狼人口历史的合并模型意味着狗的祖先种群和现存欧亚狼（16,000-64,000年前）之间可能存在广泛的分歧时间，尽管我们的点估计表明日期在25,000到33,000年前之间。除了一项针对小鼠的研究之外，我们的研究还提供了灵长类动物之外唯一直接的哺乳动物突变率，并且可能对未来突变率进化的研究至关重要。
Knowledge of mutation rates is crucial for calibrating population genetics models of demographic history in units of years. However, mutation rates remain challenging to estimate because of the need to identify extremely rare events. We estimated the nuclear mutation rate in wolves by identifying de novo mutations in a pedigree of seven wolves. Putative de novo mutations were discovered by whole-genome sequencing and were verified by Sanger sequencing of parents and offspring. Using stringent filters and an estimate of the false negative rate in the remaining observable genome, we obtain an estimate of similar to 4.5 x 10(-9) per base pair per generation and provide conservative bounds between 2.6 x 10(-9) and 7.1 x 10(-9). Although our estimate is consistent with recent mutation rate estimates from ancient DNA (4.0 x 10(-9) and 3.0-4.5 x 10(-9)), it suggests a wider possible range. We also examined the consequences of our rate and the accompanying interval for dating several critical events in canid demographic history. For example, applying our full range of rates to coalescent models of dog and wolf demographic history implies a wide set of possible divergence times between the ancestral populations of dogs and extant Eurasian wolves (16,000-64,000 years ago) although our point estimate indicates a date between 25,000 and 33,000 years ago. Aside from one study in mice, ours provides the only direct mammalian mutation rate outside of primates and is likely to be vital to future investigations of mutation rate evolution.