Molecular footprint of Medawar's mutation accumulation process in mammalian aging
文献类型：期刊论文
| 作者 | Turan, Zeliha Gozde1; Parvizi, Poorya1; Somel, Mehmet1; Parvizi, Poorya2; Donertas, Handan Melike3; Tung, Jenny4,5,6; Khaitovich, Philipp7,8; , |
| 刊名 | AGING CELL
 |
| 出版日期 | 2019 |
| 卷号 | 18期号:4页码:UNSP e12965 |
| 关键词 | aging antagonistic pleiotropy evolution gene expression genetic drift mutation accumulation protein sequence conservation |
| ISSN号 | 1474-9718 |
| DOI | 10.1111/acel.12965 |
| 文献子类 | Article |
| 英文摘要 | Medawar's mutation accumulation hypothesis explains aging by the declining force of natural selection with age: Slightly deleterious germline mutations expressed in old age can drift to fixation and thereby lead to aging-related phenotypes. Although widely cited, empirical evidence for this hypothesis has remained limited. Here, we test one of its predictions that genes relatively highly expressed in old adults should be under weaker purifying selection than genes relatively highly expressed in young adults. Combining 66 transcriptome datasets (including 16 tissues from five mammalian species) with sequence conservation estimates across mammals, here we report that the overall conservation level of expressed genes is lower at old age compared to young adulthood. This age-related decrease in transcriptome conservation (ADICT) is systematically observed in diverse mammalian tissues, including the brain, liver, lung, and artery, but not in others, most notably in the muscle and heart. Where observed, ADICT is driven partly by poorly conserved genes being up-regulated during aging. In general, the more often a gene is found up-regulated with age among tissues and species, the lower its evolutionary conservation. Poorly conserved and up-regulated genes have overlapping functional properties that include responses to age-associated tissue damage, such as apoptosis and inflammation. Meanwhile, these genes do not appear to be under positive selection. Hence, genes contributing to old age phenotypes are found to harbor an excess of slightly deleterious alleles, at least in certain tissues. This supports the notion that genetic drift shapes aging in multicellular organisms, consistent with Medawar's mutation accumulation hypothesis. |
| 学科主题 | Cell Biology ; Geriatrics & Gerontology |
| WOS关键词 | GENE-EXPRESSION PROFILES ; AGE-SPECIFIC PATTERNS ; DROSOPHILA-MELANOGASTER ; MICROARRAY ANALYSIS ; NATURAL-SELECTION ; EVOLUTION ; VARIANCE ; VERTEBRATE ; SENESCENCE ; SEQUENCE |
| 语种 | 英语 |
| WOS记录号 | WOS:000476767500014 |
| 出版者 | WILEY |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1005]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Middle East Tech Univ, Dept Biol Sci, TR-06800 Ankara, Turkey; 2.Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland; 3.European Bioinformat Inst, European Mol Biol Lab, Wellcome Trust Genome Campus, Cambridge, England; 4.Duke Univ, Dept Evolutionary Anthropol, Durham, NC USA; 5.Duke Univ, Dept Biol, Durham, NC USA; 6.Duke Univ, Duke Populat Res Inst, Durham, NC USA; 7.Skolkovo Inst Sci & Technol, Ctr Neurobiol & Brain Restorat, Moscow, Russia; 8.Chinese Acad Sci, CAS Key Lab Computat Biol, CAS MPG Partner Inst Computat Biol, Shanghai Inst Biol Sci, Shanghai, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Turan, Zeliha Gozde,Parvizi, Poorya,Somel, Mehmet,et al. Molecular footprint of Medawar's mutation accumulation process in mammalian aging[J]. AGING CELL,2019,18(4):UNSP e12965. |
| APA | Turan, Zeliha Gozde.,Parvizi, Poorya.,Somel, Mehmet.,Parvizi, Poorya.,Donertas, Handan Melike.,...&,.(2019).Molecular footprint of Medawar's mutation accumulation process in mammalian aging.AGING CELL,18(4),UNSP e12965. |
| MLA | Turan, Zeliha Gozde,et al."Molecular footprint of Medawar's mutation accumulation process in mammalian aging".AGING CELL 18.4(2019):UNSP e12965. |
入库方式： OAI收割
来源：上海营养与健康研究所
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