The Genetic Basis of Natural Variation in Caenorhabditis elegans Telomere Length

被引:75
|
作者
Cook, Daniel E. [1 ,2 ]
Zdraljevic, Stefan [1 ,2 ]
Tanny, Robyn E. [1 ]
Seo, Beomseok [6 ]
Riccardi, David D. [7 ,8 ]
Noble, Luke M. [7 ,8 ]
Rockman, Matthew V. [7 ,8 ]
Alkema, Mark J. [9 ]
Braendle, Christian [10 ]
Kammenga, Jan E. [11 ]
Wang, John [12 ]
Kruglyak, Leonid [13 ,14 ,15 ]
Felix, Marie-Anne [16 ]
Lee, Junho [6 ,17 ]
Andersen, Erik C. [1 ,3 ,4 ,5 ]
机构
[1] Northwestern Univ, Dept Mol Biosci, 2205 Tech Dr, Evanston, IL 60208 USA
[2] Northwestern Univ, Interdisciplinary Biol Sci Program, Evanston, IL 60208 USA
[3] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA
[4] Northwestern Univ, Chem Life Proc Inst, Evanston, IL 60208 USA
[5] Northwestern Univ, Northwestern Inst Complex Syst, Evanston, IL 60208 USA
[6] Seoul Natl Univ, Inst Mol Biol & Genet, Dept Biol Sci, Seoul 08826, South Korea
[7] NYU, Dept Biol, New York, NY 10003 USA
[8] NYU, Ctr Genom & Syst Biol, New York, NY 10003 USA
[9] Univ Massachusetts, Sch Med, Dept Neurobiol, Worcester, MA 01605 USA
[10] Univ Nice Sophia Antipolis, Inst Biol Valrose, INSERM, CNRS, F-06100 Nice, France
[11] Wageningen Univ, Nematol Lab, NL-6708 PB Wageningen, Netherlands
[12] Acad Sinica, Biodivers Res Ctr, Taipei 115, Taiwan
[13] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA
[14] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA
[15] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA
[16] Ecole Normale Super, Inst Biol, CNRS, INSERM, F-75005 Paris, France
[17] Seoul Natl Univ, Dept Biophys & Chem Biol, Seoul 08826, South Korea
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
Caenorhabditis elegans; QTL; shelterin; telomere length; whole-genome sequence; GENOME-WIDE ASSOCIATION; DYSKERATOSIS-CONGENITA; END; POLYMORPHISMS; ANTICIPATION; MAINTENANCE; POPULATION; LONGEVITY; ALIGNMENT; PROJECT;
D O I
10.1534/genetics.116.191148
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Telomeres are involved in the maintenance of chromosomes and the prevention of genome instability. Despite this central importance, significant variation in telomere length has been observed in a variety of organisms. The genetic determinants of telomere-length variation and their effects on organismal fitness are largely unexplored. Here, we describe natural variation in telomere length across the Caenorhabditis elegans species. We identify a large-effect variant that contributes to differences in telomere length. The variant alters the conserved oligonucleotide/oligosaccharide-binding fold of protection of telomeres 2 (POT-2), a homolog of a human telomere-capping shelterin complex subunit. Mutations within this domain likely reduce the ability of POT-2 to bind telomeric DNA, thereby increasing telomere length. We find that telomere-length variation does not correlate with offspring production or longevity in C. elegans wild isolates, suggesting that naturally long telomeres play a limited role in modifying fitness phenotypes in C. elegans.
引用
收藏
页码:371 / +
页数:18
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