A neutral theory predicts multigenic aging and increased concentrations of deleterious mutations on the mitochondrial and Y chromosomes

被引:11
作者
Cortopassi, GA [1 ]
机构
[1] Univ Calif Davis, Dept Mol Biosci, Davis, CA 95616 USA
关键词
population genetics; fixation; mutation; mitochondrial genome; free radicals;
D O I
10.1016/S0891-5849(02)00966-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Population genetic forces have molded the constitution of the human genome over evolutionary time, and some of the most important parameters are the initial frequency of the allele, p, the effective population size, Ne, and the selection coefficient, s. There is considerable agreement among evolutionary gerontologists that the amplitude of -s is small for alleles that are Deleterious In Late Life (DILL), and thus DILL traits are effectively neutral and should be fixed in the human population in relationship to Ne and p. Even higher rates of fixation of deleterious mutations are predicted to occur in the two nonrecombinant genomes in humans, i.e., the Y chromosome and the mitochondrial genome, as a consequence of their lower Ne than autosomes, and the predicted higher rate of fixation of deleterious alleles on the Y may explain the reduced average life span of males vs. females. The high probability of fixation of neutral and mildly deleterious mutations in the mitochondrial genome explains in part its fast rate of evolution, the high observed frequency of mitochondrial disease in relationship to this genome's small size, and may be the underlying reason for the transfer of mitochondrial genes over evolutionary time to the nucleus. The predicted higher concentration of deleterious mutations on the mitochondrial genome could have some leverage to cause more dysfunction than that predicted by mitochondrial gene number alone, because of the essential role of mitochondrial gene function in multisubunit complexes, the coupling of mitochondrial functions, the observation that some mtDNA sequences facilitate somatic mutation, and the likelihood of deleterious mutations either increasing the production of or the sensitivity to mitochondrial ROS. (C) 2002 Elsevier Science Inc.
引用
收藏
页码:605 / 610
页数:6
相关论文
共 29 条
[1]  
[Anonymous], 1991, Evolutionary Biology of Aging
[2]   Role of mitochondrial DNA mutations in human aging: Implications for the central nervous system and muscle [J].
Brierley, EJ ;
Johnson, MA ;
Lightowlers, RN ;
James, OFW ;
Turnbull, DM .
ANNALS OF NEUROLOGY, 1998, 43 (02) :217-223
[3]   RAPID EVOLUTION OF ANIMAL MITOCHONDRIAL-DNA [J].
BROWN, WM ;
GEORGE, M ;
WILSON, AC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1979, 76 (04) :1967-1971
[4]   MITOCHONDRIAL-DNA AND HUMAN-EVOLUTION [J].
CANN, RL ;
STONEKING, M ;
WILSON, AC .
NATURE, 1987, 325 (6099) :31-36
[5]  
Charlesworth B, 2000, GENETICS, V156, P927
[6]   The degeneration of Y chromosomes [J].
Charlesworth, B ;
Charlesworth, D .
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 2000, 355 (1403) :1563-1572
[7]  
Charlesworth B., 1994, EVOLUTION AGE STRUCT
[8]   Fixation of deleterious alleles, evolution and human aging [J].
Cortopassi, GA .
MECHANISMS OF AGEING AND DEVELOPMENT, 2002, 123 (08) :851-855
[9]   DETECTION OF A SPECIFIC MITOCHONDRIAL-DNA DELETION IN TISSUES OF OLDER HUMANS [J].
CORTOPASSI, GA ;
ARNHEIM, N .
NUCLEIC ACIDS RESEARCH, 1990, 18 (23) :6927-6933
[10]   MTDNA MUTATION IN MERRF-SYNDROME CAUSES DEFECTIVE AMINOACYLATION OF TRNA(LYS) AND PREMATURE TRANSLATION TERMINATION [J].
ENRIQUEZ, JA ;
CHOMYN, A ;
ATTARDI, G .
NATURE GENETICS, 1995, 10 (01) :47-55