Convergent genomics of longevity in rockfishes highlights the genetics of human life span variation

被引:10
作者
Treaster, Stephen [1 ,2 ]
Deelen, Joris [3 ,4 ,5 ]
Daane, Jacob M. [6 ]
Murabito, Joanne [7 ,8 ]
Karasik, David [9 ,10 ]
Harris, Matthew P. [1 ,2 ]
机构
[1] Boston Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA
[2] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA
[3] Max Planck Inst Biol Ageing, Joseph Stelzmann Str 9b, D-50931 Cologne, Germany
[4] Leiden Univ, Med Ctr, Dept Biomed Data Sci, Mol Epidemiol, Leiden, Netherlands
[5] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, Cologne, Germany
[6] Univ Houston, Dept Biol & Biochem, Houston, TX USA
[7] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med, Boston, MA 02118 USA
[8] Framingham Heart Dis Epidemiol Study, Framingham, MA USA
[9] Bar Ilan Univ, Azrieli Fac Med, Safed, Israel
[10] Hebrew Senior Life, Marcus Inst Aging Res, Boston, MA USA
基金
美国国家科学基金会;
关键词
PHOSPHOLIPASE A(2); MOUSE MODELS; EVOLUTION; PATHWAY; METABOLISM; ACTIVATION; EXPRESSION; SULFATION; SEBASTES; LONG;
D O I
10.1126/sciadv.add2743
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Longevity is a defining, heritable trait that varies dramatically between species. To resolve the genetic regulation of this trait, we have mined genomic variation in rockfishes, which range in longevity from 11 to over 205 years. Multiple shifts in rockfish longevity have occurred independently and in a short evolutionary time frame, thus empowering convergence analyses. Our analyses reveal a common network of genes under convergent evolution, encompassing established aging regulators such as insulin signaling, yet also identify flavonoid (aryl-hydrocarbon) metabolism as a pathway modulating longevity. The selective pressures on these pathways indicate the ancestral state of rockfisheswas long lived and that the changes in short-lived lineages are adaptive. These pathways were also used to explore genome-wide association studies of human longevity, identifying the aryl-hydrocarbon metabolism pathway to be significantly associated with human survival to the 99th percentile. This evolutionary intersection defines and cross-validates a previously unappreciated genetic architecture that associates with the evolution of longevity across vertebrates.
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页数:14
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