Abstract
The molecular clock hypothesis is a central concept in molecular evolution and has inspired much research into why evolutionary rates vary between and within genomes. In the age of modern comparative genomics, understanding the neutral genomic molecular clock occupies a critical place. It has been demonstrated that molecular clocks run differently between closely related species, and generation time is an important determinant of lineage specific molecular clocks. Moreover, it has been repeatedly shown that regional molecular clocks vary even within a genome, which should be taken into account when measuring evolutionary constraint of specific genomic regions. With the availability of a large amount of genomic sequence data, new insights into the patterns and causes of variation in molecular clocks are emerging. In particular, factors such as nucleotide composition, molecular origins of mutations, weak selection and recombination rates are important determinants of neutral genomic molecular clocks.
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References
Akashi, H. (1994). Synonymous codon usage in Drosophila melanogaster: Natural selection and translational accuracy. Genetics, 136(3), 927–935.
Akashi, H. (2001). Gene expression and molecular evolution. Current Opinion in Genetics & Development, 11, 660–666.
Birdsell, J. A. (2002). Integrating genomics, bioinformatics, and classical genetics to study the effects of recombination on genome evolution. Molecular Biology and Evolution, 19, 1181–1197.
Bohossian, H. B., Skaletsky, H., & Page, D. C. (2000). Unexpectedly similar rates of nucleotide substitution found in male and female hominids. Nature, 406, 622–625.
Britten, R. J. (1986). Rates of DNA sequence evolution differ between taxonomic groups. Science, 231, 1393–1398.
Bromham, L., & Penny, D. (2003). The modern molecular clock. Nature Reviews Genetics, 4, 216–224.
Cannarozzi, G., Schneider, A., & Gonnet, G. (2007). A phylogenomic study of human, dog and mouse. PLoS Computational Biology, 3(1), e2.
Castresana, J. (2002). Estimation of genetic distances from human and mouse introns. Genome Biology, 3(6), research0028.1–0028.7.
Chamary, J. V., Parmley, J. L., & Hurst, L. D. (2006). Hearing silence: Non-neutral evolution at synonymous sites in mammals. Nature Reviews Genetics, 7, 98–108.
Chang, B. H., Shimmin, L. C., Shyue, S.-K., Hewett-Emmett, D., & Li, W.-H. (1994). Weak male-driven molecular evolution in rodents. Proceedings of the National Academy of Sciences of the United States of America, 91, 827–831.
Chen, F. C., & Li, W.-H. (2001). Genomic divergence between humans and other hominoids and the effective population size of the common ancestor of humans and chimpanzees. American Journal of Human Genetics, 68, 444–456.
Cheng, J., Kapranov, P., Drenkow, J., Dike, S., Brubaker, S., Patel, S., et al. (2005). Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science, 308(5725), 1149–1154.
Chimpanzee Sequencing and Analysis Consortium. (2005). Initial sequence of the chimpanzee genome and comparison with the human genome. Nature, 437, 69–87.
Dermitzakis, E. T., Reymond, A., Lyle, R., Scamuffa, N., Ucla, C., Deutsch, S., et al. (2002). Numerous potentially functional but non-genic conserved sequences on human chromosome 21. Nature, 420, 578–582.
Drummond, D. A., Bloom, J. D., Adami, C., Wilke, C. O., & Arnod, F. H. (2005). Why highly expressed proteins evolve slowly. Proceedings of the National Academy of Sciences of the United States of America, 102, 14338–14343.
Easteal, S. (1991). The relative ratae of DNA evolution in primates. Molecular Biology and Evolution, 8(1), 115–127.
Ellegren, H., & Fridolfsson, A. K. (1997). Male-driven evolution of DNA sequences in birds. Nature Genetics, 17, 182–184.
Filipski, J. (1988). Why the rate of silent codon substitutions is variable within a vertebrate’s genome. Journal of Theoretical Biology, 134(2), 159–164.
Fullerton, S. M., Bernardo-Carvalho, A., & Clark, A. G. (2001). Local rates of recombination are positively correlated with GC content in the human genome. Molecular Biology and Evolution, 18(6), 1139–1142.
Galtier, N., Piganeau, G., Mouchiroud, D., & Duret, L. (2001). GC-content evolution in mammalian genomes: The biased gene conversion hypothesis. Genetics, 159, 907–911.
Goodman, M. (1961). The role of immunologic differences in the phyletic development of human behavior. Human Biology, 33, 131–162.
Goodman, M. (1962). Evolution of the immunologic species specificity of human serum proteins. Human Biology, 34, 104–150.
Gu, X., & Li, W.-H. (1992). Higher rates of amino acid substitution in rodents than in humans. Molecular Phylogenetics and Evolution, 1(3), 211–214.
Hellmann, I., Ebersberger, I., Ptak, S. E., Paabo, S., & Przeworski, M. (2003). A neutral explanation for the correlation of diversity with recombination rates in humans. American Journal of Human Genetics, 72(6), 1527–1535.
Huang, S.-W., Friedman, R., Yu, N., Yu, A., & Li, W.-H. (2005). How strong is the mutagenicity of recombination in mammals? Molecular Biology and Evolution, 22(3), 426–431.
Huttley, G. A., Wakefield, M. J., & Easteal, S. (2007). Rates of genome evolution and branching order from whole genome analysis. Molecular Biology and Evolution, 24, 1772–1730.
Jeffreys, A. J., Holloway, J. K., Kauppi, L., May, C. A., Neumann, R., Timothy Slingsby, M., et al. (2004). Meiotic recombination hot spots and human DNA diversity. Philosophical Transactions of the Royal Society London, B., 359, 141–152.
Jeffreys, A. J., Kauppi, L., & Neumann, R. (2001). Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex. Nature Genetics, 29, 217–222.
Jensen-Seaman, M. I., Furey, T. S., Payseur, B. A., Lu, Y., Roskin, K. M., Chen, C.-F., et al. (2004). Comparative recombination rates in the rat, mouse, and human genomes. Genome Research, 14(4), 528–538.
Jones, P. A., & Takai, D. (2001). The role of DNA methylation in mammalian epigenetics. Science, 293, 1068–1070.
Keightley, P. D., Lercher, M. J., & Eyre-Walker, A. (2005). Evidence for widespread degradation of gene control regions in hominoid genomes. PLoS Biology, 3, e42.
Kim, S.-H., Elango, N., Warden, C. W., Vigoda, E., & Yi, S. (2006). Heterogenous genomic molecular clocks in primates. PLoS Genetics, 2, e163.
Kimura, M. (1983). The neutral theory of molecular evolution. Cambridge, UK: Cambridge University Press.
Kohne, C. (1970). Evolution of higher-organism DNA. Quarterly Reviews of Biophysics, 3, 327–375.
Kondrashov, F. A., Ogurtsov, A. Y., & Kondrashov, A. S. (2006). Selection in favor of nucleotides G and C diversifies evolution rates and levels of polymorphism at mammalian synonymous sites. Journal of Theoretical Biology, 240, 616–626.
Kong, A., Gudbhartsson, D. F., Sainz, J., Jonsdottir, G. M., Gudjonsson, S. A., Richardsson, B., et al. (2002). A high-resolution recombination map of the human genome. Nature Genetics, 31, 241–247.
Kumar, S. (2005). Molecular clocks: Four decades of evolution. Nature Reviews Genetics, 6, 654–662.
Kumar, S., & Subramanian, S. (2002). Mutation rates in mammalian genomes. Proceedings of the National Academy of Sciences of the United States of America, 99(2), 803–808.
Laird, C. D., McConaughy, B. L., & McCarthy, B. J. (1969). Rate of fixation of nucleotide substitutions in evolution. Nature, 224, 149–154.
Lercher, M. J., & Hurst, L. D. (2002). Human SNP variability and mutation rate are higher in regions of high recombination. Trends in Genetics, 18(7), 337–340.
Li, W.-H. (1997). Molecular evolution. Sunderland, MA: Sinauer.
Li, E. (2002). Chromatin modification and epigenetic reprogramming in mammalian development. Nature Reviews Genetics, 3, 662–673.
Li, W.-H., Ellsworth, D. L., Krushkal, J., Chang, B. H.-J., & Hewett-Emmett, D. (1996). Rates of nucleotide substitution in primates and rodents and the generation-time effect hypothesis. Molecular Phylogenetics and Evolution, 5(1), 182–187.
Li, W.-H., Tanimura, M., & Sharp, P. M. (1987). An evaluation of the molecular clock hypothesis using mammalian DNA sequences. Journal of Molecular Evolution, 25, 330–342.
Li, W.-H., Yi, S., & Makova, K. (2002). Male-driven evolution. Current Opinion in Genetics & Development, 12(6), 650–656.
Makova, K. D., & Li, W.-H. (2002). Strong male-driven evolution of DNA sequences in humans and apes. Nature, 416, 624–626.
Margoliash, E. (1963). Primary structure and evolution of cytochrome C. Proceedings of the National Academy of Sciences of the United States of America, 50, 672–679.
McVean, G. A. T., Myers, S. R., Hunt, S., Deloukas, P., Bentley, D. R., & Donnelly, P. (2004). The fine-scale structure of recombination rate variation in the human genome. Science, 304, 581–584.
Meunier, J., & Duret, L. (2004). Recombination drives the evolution of GC-content in the human genome. Molecular Biology and Evolution, 21(6), 984–990.
Montoya-Burgos, J. I., Boursot, P., & Galtier, N. (2003). Recombination explains isochores in mammalian genomes. Trends in Genetics, 19, 128–130.
Murphy, W. J., Eizirik, E., O’Brien, S. J., Madsen, O., Scally, M., Douady, C. J., et al. (2001). Resoluion of the early placental mammal radiation using Bayesian phylogenetics. Science, 294, 2348–2351.
Myers, S., Bottolo, L., Frreeman, C., McVean, G., & Donnelly, P. (2005). A fine-scale map of recombination rates and hotspots across the human genome. Science, 310(Oct. 14), 321–324.
Nachman, M. W., & Crowell, S. L. (2000). Estimate of the mutation rate per nucleotide in humans. Genetics, 156(1), 297–304.
Patterson, N., Richter, D. J., Gnerre, S., Lander, E. S., & Reich, D. (2006). Genetic evidence for complex speciation of humans and chimpanzees. Nature, 441, 1103–1108.
Perry, J., & Ashworth, A. (1999). Evolutionary rate of a gene affected by chromosomal position. Current Biology, 9, 987–989.
Pollard, K. S., Salama, S. R., Lambert, N., Lambot, M.-A., Coppens, S., Pedersen, J. S., et al. (2006). An RNA gene expressed during cortical development evolved rapidly in humans. Nature, 443, 167–172.
Ptak, S. E., Hinds, D. A., Koehler, K., Nickel, B., Patil, N., Ballinger, D. G., et al. (2005). Fine-scale recombination patterns differ between chimpanzees and humans. Nature Genetics, 37(4), 429–434.
Rogers, J., Mahaney, M. C., et al. (2000). A genetic linkage map of the baboon (Papio hamadryas) genome based on human microsatellite polymorphisms. Genomics, 67, 237–247.
Sarich, V. M., & Wilson, A. C. (1967). Immunological tie scale for hominid evolution. Science, 158, 1200–1203.
Semon, M., & Duret, L. (2004). Evidence that functional transcription units cover at least half of the human genome. Trends in Genetics, 20, 229–232.
Shimmin, L. C., Chang, B. H., & Li, W.-H. (1993). Male-driven evolution of DNA sequences. Nature, 362, 745–747.
Steiper, M. E., & Young, N. M. (2006). Primate molecular divergence dates. Molecular Phylogenetics and Evolution, 41, 384–394.
Steiper, M. E., Young, N. M., & Sukrarna, T. Y. (2004). Genomic data support the hominoid slowdown and an early Oligocene estimate for the hominoid-cercopithecoid divergence. Proceedings of the National Academy of Sciences of the United States of America, 101, 17021–17026.
Subramanian, S., & Kumar, S. (2003). Neutral substitutions occur at a faster rate in exons than in noncoding DNA in primate genomes. Genome Research, 13, 838–844.
Winckler, W., Myers, S. R., Richter, D. J., Onofrio, R. C., McDonald, G. J., Bontrop, R. E., et al. (2005). Comparison of fine-scale recombination rates in humans and chimpanzees. Science, 308(5718), 107–111.
Wolfe, K. H., Sharp, P. M., & Li, W.-H. (1989). Mutation rates differ among regions of the mammalian genome. Nature, 337, 283–285.
Wu, C.-I., & Li, W.-H. (1985). Evidence for higher rates of nucleotide substitution in rodents than in man. Proceedings of the National Academy of Sciences of the United States of America, 82, 1741–1745.
Yi, S., Ellsworth, D. L., & Li, W.-H. (2002). Slow molecular clocks in Old World monkeys, apes, and humans. Molecular Biology and Evolution, 19(12), 2191–2198.
Yi, S., & Li, W.-H. (2005). Molecular evolution of recombination hotspots and highly recombining pseudoautosomal regions in hominoids. Molecular Biology and Evolution, 22, 1223–1230.
Yi, S., Summers, T. J., Pearson, N. M., & Li, W.-H. (2004). Recombination has little effect on the rate of sequence divergence in pseudoausotomal boundary 1 among humans and great apes. Genome Research, 14, 37–43.
Zuckerkandl, E., & Pauling, L. B. (1962). Molecular disease, evolution, and genetic heterogeneity. In M. Kasha & B. Pullman (Eds.), Horizons in biochemistry (pp. 189–225). New York: Academic Press.
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Yi, S.V. Understanding Neutral Genomic Molecular Clocks. Evol Biol 34, 144–151 (2007). https://doi.org/10.1007/s11692-007-9010-7
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DOI: https://doi.org/10.1007/s11692-007-9010-7