气候变化领域集成服务门户(CCPortal): The evolutionary dynamics and fitness landscape of clonal hematopoiesis

CCPortal

DOI	10.1126/science.aay9333
	The evolutionary dynamics and fitness landscape of clonal hematopoiesis
	Watson C.J.; Papula A.L.; Poon G.Y.P.; Wong W.H.; Young A.L.; Druley T.E.; Fisher D.S.; Blundell J.R.
发表日期	2020
ISSN	0036-8075
起始页码	1449
结束页码	1454
卷号	367 期号:6485
英文摘要	Somatic mutations acquired in healthy tissues as we age are major determinants of cancer risk. Whether variants confer a fitness advantage or rise to detectable frequencies by chance remains largely unknown. Blood sequencing data from ~50,000 individuals reveal how mutation, genetic drift, and fitness shape the genetic diversity of healthy blood (clonal hematopoiesis). We show that positive selection, not drift, is the major force shaping clonal hematopoiesis, provide bounds on the number of hematopoietic stem cells, and quantify the fitness advantages of key pathogenic variants, at single-nucleotide resolution, as well as the distribution of fitness effects (fitness landscape) within commonly mutated driver genes. These data are consistent with clonal hematopoiesis being driven by a continuing risk of mutations and clonal expansions that become increasingly detectable with age. © 2020 American Association for the Advancement of Science. All rights reserved.
关键词	DNA methyltransferase 3A blood cancer evolutionary biology fitness gene expression genetic drift hematology mutation pathogenicity acute myeloid leukemia age distribution allele Article cancer risk cell expansion cell population clonal hematopoiesis epigenetics gene mutation genetic variability hematological parameters hematopoiesis hematopoietic stem cell human molecular evolution mutational analysis nonhuman priority journal single nucleotide polymorphism somatic mutation stem cell self-renewal
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133598
推荐引用方式 GB/T 7714	Watson C.J.,Papula A.L.,Poon G.Y.P.,et al. The evolutionary dynamics and fitness landscape of clonal hematopoiesis[J]. Science,2020,367(6485).
APA	Watson C.J..,Papula A.L..,Poon G.Y.P..,Wong W.H..,Young A.L..,...&Blundell J.R..(2020).The evolutionary dynamics and fitness landscape of clonal hematopoiesis.,367(6485).
MLA	Watson C.J.,et al."The evolutionary dynamics and fitness landscape of clonal hematopoiesis".367.6485(2020).