Molecular Biology and Evolution 19:2191-2198 (2002)
© 2002 Society for Molecular Biology and Evolution
Slow Molecular Clocks in Old World Monkeys, Apes, and Humans

*Department of Ecology and Evolution, University of Chicago;
Windber Research Institute, Windber, Pennsylvania
Two longstanding issues on the molecular clock hypothesis are studied in this article. First, is there a global molecular clock in mammals? Although many authors have observed unequal rates of nucleotide substitution among mammalian lineages, some authors have proposed a global clock for all eutherians, i.e., a single global rate of 2.2 x 10-9 substitutions per nucleotide site per year. We reexamine this issue using noncoding, nonrepetitive DNA from Old World monkeys (OWMs), chimpanzee, and human. First, using the minimal date of 6 MYA for the human-chimpanzee divergence and more than 2.5 million base pairs of genomic sequences from human and chimpanzee, we estimate a maximal rate of 0.99 x 10-9 for noncoding, nonrepetitive genomic regions for these two species. This estimate is less than half of the proposed global rate and much smaller than the commonly used rate (3.5 x 10-9) for eutherians. Further, using a minimal date of 23 MYA for the human-OWM divergence, we estimate a maximal rate of 1.5 x 10-9 for both introns and fourfold degenerate sites in humans and OWMs. In addition, with the New World monkey (NWM) lineage as an outgroup, we estimate that the rate of substitution in introns is 30% higher in the OWM lineage than in the human lineage. Clearly, there is no global molecular clock in eutherians. Second, although many studies have indicated considerable variation in the mutation rate among regions of the mammalian genome, a recent study proposed a uniform rate. Using new and existing intron sequence data from higher primates, we find significant rate variation among genomic regions and a positive correlation between the rate of substitution and the GC content, refuting the claim of a uniform rate.
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
C. Tsantes and M. E. Steiper Age at first reproduction explains rate variation in the strepsirrhine molecular clock PNAS, October 27, 2009; 106(43): 18165 - 18170. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Elango, J. Lee, Z. Peng, Y.-H. E. Loh, and S. V. Yi Evolutionary rate variation in Old World monkeys Biol Lett, June 23, 2009; 5(3): 405 - 408. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Peifer, J. E. Karro, and H. H. von Grunberg Is there an acceleration of the CpG transition rate during the mammalian radiation? Bioinformatics, October 1, 2008; 24(19): 2157 - 2164. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Burgess and Z. Yang Estimation of Hominoid Ancestral Population Sizes under Bayesian Coalescent Models Incorporating Mutation Rate Variation and Sequencing Errors Mol. Biol. Evol., September 1, 2008; 25(9): 1979 - 1994. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. M. Miller-Butterworth, J. R. Kaplan, J. Shaffer, B. Devlin, S. B. Manuck, and R. E. Ferrell Sequence Variation in the Primate Dopamine Transporter Gene and Its Relationship to Social Dominance Mol. Biol. Evol., January 1, 2008; 25(1): 18 - 28. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. I. Nikolaev, J. I. Montoya-Burgos, K. Popadin, L. Parand, E. H. Margulies, National Institutes of Health Intramural Sequencin, and S. E. Antonarakis Life-history traits drive the evolutionary rates of mammalian coding and noncoding genomic elements PNAS, December 18, 2007; 104(51): 20443 - 20448. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. W. Hahn, J. P. Demuth, and S.-G. Han Accelerated Rate of Gene Gain and Loss in Primates Genetics, November 1, 2007; 177(3): 1941 - 1949. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. V. Babushok, K. Ohshima, E. M. Ostertag, X. Chen, Y. Wang, P. K. Mandal, N. Okada, C. S. Abrams, and H. H. Kazazian Jr. A novel testis ubiquitin-binding protein gene arose by exon shuffling in hominoids Genome Res., August 1, 2007; 17(8): 1129 - 1138. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. K. Pace II and C. Feschotte The evolutionary history of human DNA transposons: Evidence for intense activity in the primate lineage Genome Res., April 1, 2007; 17(4): 422 - 432. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. J. Pritham and C. Feschotte Massive amplification of rolling-circle transposons in the lineage of the bat Myotis lucifugus PNAS, February 6, 2007; 104(6): 1895 - 1900. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Dupanloup and H. Kaessmann Evolutionary simulations to detect functional lineage-specific genes Bioinformatics, August 1, 2006; 22(15): 1815 - 1822. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Dorus, J. R. Anderson, E. J. Vallender, S. L. Gilbert, L. Zhang, L. G. Chemnick, O. A. Ryder, W. Li, and B. T. Lahn Sonic Hedgehog, a key development gene, experienced intensified molecular evolution in primates Hum. Mol. Genet., July 1, 2006; 15(13): 2031 - 2037. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Elango, J. W. Thomas, NISC Comparative Sequencing Program, and S. V. Yi Variable molecular clocks in hominoids PNAS, January 31, 2006; 103(5): 1370 - 1375. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Kumar, A. Filipski, V. Swarna, A. Walker, and S. B. Hedges Placing confidence limits on the molecular age of the human-chimpanzee divergence PNAS, December 27, 2005; 102(52): 18842 - 18847. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Rowen, E. Williams, G. Glusman, E. Linardopoulou, C. Friedman, M. E. Ahearn, J. Seto, C. Boysen, S. Qin, K. Wang, et al. Interchromosomal Segmental Duplications Explain the Unusual Structure of PRSS3, the Gene for an Inhibitor-Resistant Trypsinogen Mol. Biol. Evol., August 1, 2005; 22(8): 1712 - 1720. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. H. Perry, B. C. Verrelli, and A. C. Stone Comparative Analyses Reveal a Complex History of Molecular Evolution for Human MYH16 Mol. Biol. Evol., March 1, 2005; 22(3): 379 - 382. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Zhang On the Evolution of Codon Volatility Genetics, January 1, 2005; 169(1): 495 - 501. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. E. Steiper, N. M. Young, and T. Y. Sukarna Genomic data support the hominoid slowdown and an Early Oligocene estimate for the hominoid-cercopithecoid divergence PNAS, December 7, 2004; 101(49): 17021 - 17026. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Abe, H. Noguchi, K. Tagawa, M. Yuzuriha, A. Toyoda, T. Kojima, K. Ezawa, N. Saitou, M. Hattori, Y. Sakaki, et al. Contribution of Asian mouse subspecies Mus musculus molossinus to genomic constitution of strain C57BL/6J, as defined by BAC-end sequence-SNP analysis Genome Res., December 1, 2004; 14(12): 2439 - 2447. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Howell, J. L. Elson, D. M. Turnbull, and C. Herrnstadt African Haplogroup L mtDNA Sequences Show Violations of Clock-like Evolution Mol. Biol. Evol., October 1, 2004; 21(10): 1843 - 1854. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Lercher, J.-V. Chamary, and L. D. Hurst Genomic Regionality in Rates of Evolution Is Not Explained by Clustering of Genes of Comparable Expression Profile Genome Res., June 1, 2004; 14(6): 1002 - 1013. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. W. Hahn, M. V. Rockman, N. Soranzo, D. B. Goldstein, and G. A. Wray Population Genetic and Phylogenetic Evidence for Positive Selection on Regulatory Mutations at the Factor VII Locus in Humans Genetics, June 1, 2004; 167(2): 867 - 877. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Zhang, X. Wang, and O. Podlaha Testing the Chromosomal Speciation Hypothesis for Humans and Chimpanzees Genome Res., May 1, 2004; 14(5): 845 - 851. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Fischer, V. Wiebe, S. Paabo, and M. Przeworski Evidence for a Complex Demographic History of Chimpanzees Mol. Biol. Evol., May 1, 2004; 21(5): 799 - 808. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Le Jossec, T. Wambach, D. Labuda, D. Sinnett, and E. Levy Genetic Diversity Patterns in the SR-BI/II Locus Can Be Explained by a Recent Selective Sweep Mol. Biol. Evol., April 1, 2004; 21(4): 760 - 769. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. A. Filatov A Gradient of Silent Substitution Rate in the Human Pseudoautosomal Region Mol. Biol. Evol., February 1, 2004; 21(2): 410 - 417. [Abstract] [Full Text] [PDF] |
||||
![]() |
WHEN CLOCKS (AND COMMUNITIES) COLLIDE: ESTIMATING DIVERGENCE TIME FROM MOLECULES AND THE FOSSIL RECORD Journal of Paleontology, January 1, 2004; 78(1): 1 - 6. |
||||
![]() |
J. Zhang Evolution of the Human ASPM Gene, a Major Determinant of Brain Size Genetics, December 1, 2003; 165(4): 2063 - 2070. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. F. Arndt, D. A. Petrov, and T. Hwa Distinct Changes of Genomic Biases in Nucleotide Substitution at the Time of Mammalian Radiation Mol. Biol. Evol., November 1, 2003; 20(11): 1887 - 1896. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Zhang and D. M. Webb Evolutionary deterioration of the vomeronasal pheromone transduction pathway in catarrhine primates PNAS, July 8, 2003; 100(14): 8337 - 8341. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. D. Makova and W.-H. Li Divergence in the Spatial Pattern of Gene Expression Between Human Duplicate Genes Genome Res., July 1, 2003; 13(7): 1638 - 1645. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. E. Wildman, M. Uddin, G. Liu, L. I. Grossman, and M. Goodman Inaugural Article: Implications of natural selection in shaping 99.4% nonsynonymous DNA identity between humans and chimpanzees: Enlarging genus Homo PNAS, June 10, 2003; 100(12): 7181 - 7188. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Subramanian and S. Kumar Neutral Substitutions Occur at a Faster Rate in Exons Than in Noncoding DNA in Primate Genomes Genome Res., May 1, 2003; 13(5): 838 - 844. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Navarro and N. H. Barton Chromosomal Speciation and Molecular Divergence--Accelerated Evolution in Rearranged Chromosomes Science, April 11, 2003; 300(5617): 321 - 324. [Abstract] [Full Text] [PDF] |
||||








