Somatic mutation rates scale with lifespan across mammals.
Somatic mutation rates scale with lifespan across mammals.
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DOI：
10.1038/s41586-022-04618-z
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发表时间：
2022-04
期刊：
影响因子：
64.8
通讯作者：
中科院分区：
文献类型：
--
作者：
正常组织中体细胞突变的速率和模式在人类之外基本上是未知的。比较分析可以揭示物种间诱变的多样性，以及关于体细胞突变率进化及其在癌症和衰老中的作用的长期假设。在这里，我们对来自56个个体的208个肠隐窝进行了全基因组测序，以研究16种哺乳动物物种的体细胞突变景观。我们发现体细胞诱变在所有物种中都是由看似内源性的突变过程主导的，包括5-甲基胞嘧啶脱胺和氧化损伤。其他物种的突变特征与人类相似，但存在一些差异，尽管每种特征的相对贡献在不同物种之间有所不同。值得注意的是，每年体细胞突变率在物种之间差异很大，并且与物种寿命呈强烈的反比关系，没有其他生活史特征研究显示出可比的相关性。尽管我们研究的物种之间的生活史差异很大——包括寿命的30倍左右和体重的4万倍左右——但在寿命结束时，体细胞突变负担的变化仅为3倍左右。这些数据揭示了哺乳动物共同的突变过程，并表明体细胞突变率在进化上受到限制，可能是衰老的一个促成因素。全基因组测序用于分析来自16种哺乳动物物种的肠隐窝体细胞突变的景观，揭示了跨物种的体细胞突变率与动物的寿命成反比。
The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans. Comparative analyses can shed light on the diversity of mutagenesis across species, and on long-standing hypotheses about the evolution of somatic mutation rates and their role in cancer and ageing. Here we performed whole-genome sequencing of 208 intestinal crypts from 56 individuals to study the landscape of somatic mutation across 16 mammalian species. We found that somatic mutagenesis was dominated by seemingly endogenous mutational processes in all species, including 5-methylcytosine deamination and oxidative damage. With some differences, mutational signatures in other species resembled those described in humans, although the relative contribution of each signature varied across species. Notably, the somatic mutation rate per year varied greatly across species and exhibited a strong inverse relationship with species lifespan, with no other life-history trait studied showing a comparable association. Despite widely different life histories among the species we examined—including variation of around 30-fold in lifespan and around 40,000-fold in body mass—the somatic mutation burden at the end of lifespan varied only by a factor of around 3. These data unveil common mutational processes across mammals, and suggest that somatic mutation rates are evolutionarily constrained and may be a contributing factor in ageing. Whole-genome sequencing is used to analyse the landscape of somatic mutation in intestinal crypts from 16 mammalian species, revealing that rates of somatic mutation inversely scale with the lifespan of the animal across species.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
12.3
作者：
Blokzijl F;Janssen R;van Boxtel R;Cuppen E
通讯作者：
Cuppen E
影响因子：
10.7
作者：
Lopez, Elora H.;Palumbi, Stephen R.
通讯作者：
Palumbi, Stephen R.
影响因子：
7.7
作者：
Ju YS;Alexandrov LB;Gerstung M;Martincorena I;Nik-Zainal S;Ramakrishna M;Davies HR;Papaemmanuil E;Gundem G;Shlien A;Bolli N;Behjati S;Tarpey PS;Nangalia J;Massie CE;Butler AP;Teague JW;Vassiliou GS;Green AR;Du MQ;Unnikrishnan A;Pimanda JE;Teh BT;Munshi N;Greaves M;Vyas P;El-Naggar AK;Santarius T;Collins VP;Grundy R;Taylor JA;Hayes DN;Malkin D;ICGC Breast Cancer Group;ICGC Chronic Myeloid Disorders Group;ICGC Prostate Cancer Group;Foster CS;Warren AY;Whitaker HC;Brewer D;Eeles R;Cooper C;Neal D;Visakorpi T;Isaacs WB;Bova GS;Flanagan AM;Futreal PA;Lynch AG;Chinnery PF;McDermott U;Stratton MR;Campbell PJ
通讯作者：
Campbell PJ
正常细胞的基因组测序揭示了发育谱系和突变过程。
影响因子：
64.8
作者：
Behjati, Sam;Huch, Meritxell;van Boxtel, Ruben;Karthaus, Wouter;Wedge, David C.;Tamuri, Asif U.;Martincorena, Inigo;Petljak, Mia;Alexandrov, Ludmil B.;Gundem, Gunes;Tarpey, Patrick S.;Roerink, Sophie;Blokker, Joyce;Maddison, Mark;Mudie, Laura;Robinson, Ben;Nik-Zainal, Serena;Campbell, Peter;Goldman, Nick;van de Wetering, Marc;Cuppen, Edwin;Clevers, Hans;Stratton, Michael R.
通讯作者：
Stratton, Michael R.