r8s: inferring absolute rates of molecular evolution and divergence times in the absence of a molecular clock
Abstract
Summary Estimating divergence times and rates of substitution from sequence data is plagued by the problem of rate variation between lineages. R8s version 1.5 is a program which uses parametric, nonparametric and semiparametric methods to relax the assumption of constant rates of evolution to obtain better estimates of rates and times. Unlike most programs for rate inference or phylogenetics, r8s permits users to convert results to absolute rates and ages by constraining one or more node times to be fixed, minimum or maximum ages (using fossil or other evidence). Version 1.5 uses truncated Newton nonlinear optimization code with bound constraints, offering superior performance over previous versions. Availability The linux executable, C source code, sample data sets and user manual are available free at http://ginger.ucdavis.edu/r8s.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Cites
The Elements of Statistical Learning
Hastie, T., Tibshirani, R., & Friedman, J. (2009) · Springer Series in Statistics · doi:10.1007/978-0-387-84858-7 · Cited by 25,970 · see citing works
Sanderson, M. J. (2002) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a003974 · Cited by 1,977 · see citing works
Self-citationGill, P. E., Murray, W., & Wright, M. H. (2019) · doi:10.1137/1.9781611975604 · Cited by 1,737 · cited 1× · see citing works
“Older versions of r8s implemented bound constraints using general nonlinear constraint methods such as barrier/penalty functions (Gill et al., 1981), with optimization relying on Powell’s method without gradients.”
MethodEstimating the rate of evolution of the rate of molecular evolution
Thorne, J. L., Kishino, H., & Painter, I. S. (1998) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a025892 · Cited by 1,317 · see citing works
A nonparametric approach to estimating divergence times in the absence of rate constancy.
Sanderson, M. J. (1997) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a025731 · Cited by 1,156 · see citing works
Self-citationPerformance of a divergence time estimation method under a probabilistic model of rate evolution.
Kishino, H., Thorne, J. L., & Bruno, W. J. (2001) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a003811 · Cited by 633 · cited 4× · see citing works
“This has prompted considerable work aimed at developing methods for estimating rates and times in the absence of a clock (Huelsenbeck et al. , 2000; Kishino et al. , 2001; Rambaut and Bromham, 1998; Sanderson, 1997, 2002; Takezaki et al. , 1995; Thorne et al. , 1998).”
InfluentialMolecular Evidence for Deep Precambrian Divergences Among Metazoan Phyla
Wray, G. A., Levinton, J. S., & Shapiro, L. H. (1996) · Science · doi:10.1126/science.274.5287.568 · Cited by 511 · see citing works
Nei, M., Xu, P., & Glazko, G. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051611498 · Cited by 329 · see citing works
Estimating divergence dates from molecular sequences.
Rambaut, A., & Bromham, L. (1998) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a025940 · Cited by 298 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
O'Connell, R. J., Thon, M. R., Hacquard, S., Amyotte, S. G., Kleemann, J., Torres, M. F., Damm, U., Buiate, E. A., Epstein, L., Alkan, N., et al. (2012) · Nature Genetics · doi:10.1038/ng.2372 · Cited by 1,047 · see citing works
A Molecular Timeline for the Origin of Photosynthetic Eukaryotes
Yoon, H. S., Hackett, J. D., Ciniglia, C., Pinto, G., & Bhattacharya, D. (2004) · Molecular Biology and Evolution · doi:10.1093/molbev/msh075 · Cited by 945 · see citing works
Recalibrating equus evolution using the genome sequence of an early middle pleistocene horse
Orlando, L., Ginolhac, A., Zhang, G., Froese, D., Albrechtsen, A., Stiller, M., Schubert, M., Cappellini, E., Petersen, B., Moltke, I., et al. (2013) · Nature · doi:10.1038/nature12323 · Cited by 841 · see citing works
Reading the entrails of chickens: molecular timescales of evolution and the illusion of precision
Graur, D., & Martin, W. (2004) · Trends in Genetics · doi:10.1016/j.tig.2003.12.003 · Cited by 669 · see citing works
A molecular timescale of eukaryote evolution and the rise of complex multicellular life
Hedges, S. B., Blair, J. E., Venturi, M. L., & Shoe, J. L. (2004) · BMC Evolutionary Biology · doi:10.1186/1471-2148-4-2 · Cited by 578 · see citing works
Repeated morphological evolution through cis-regulatory changes in a pleiotropic gene
Prud'homme, B., Gompel, N., Rokas, A., Kassner, V. A., Williams, T. M., Yeh, S.-D., True, J. R., & Carroll, S. B. (2006) · Nature · doi:10.1038/nature04597 · Cited by 507 · see citing works
Large-scale ruminant genome sequencing provides insights into their evolution and distinct traits
Chen, L., Qiu, Q., Jiang, Y., Wang, K., Lin, Z., Li, Z., Bibi, F., Yang, Y., Wang, J., Nie, W., et al. (2019) · Science · doi:10.1126/science.aav6202 · Cited by 441 · see citing works
Angiosperm diversification through time
Magallón, S., & Castillo, A. (2009) · American Journal of Botany · doi:10.3732/ajb.0800060 · Cited by 439 · see citing works
Phylogenomics reveals three sources of adaptive variation during a rapid radiation
Pease, J. B., Haak, D. C., Hahn, M. W., & Moyle, L. C. (2016) · PLOS Biology · doi:10.1371/journal.pbio.1002379 · Cited by 432 · see citing works
Bayesian molecular clock dating of species divergences in the genomics era
dos Reis, M., Donoghue, P. C. J., & Yang, Z. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2015.8 · Cited by 339 · see citing works
Prehistoric genomes reveal the genetic foundation and cost of horse domestication
Schubert, M., Jónsson, H., Chang, D., Der Sarkissian, C., Ermini, L., Ginolhac, A., Albrechtsen, A., Dupanloup, I., Foucal, A., Petersen, B., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1416991111 · Cited by 324 · see citing works
BLANK, C. E., & SÁNCHEZ‐BARACALDO, P. (2010) · Geobiology · doi:10.1111/j.1472-4669.2009.00220.x · Cited by 298 · see citing works
Primate jumping genes elucidate strepsirrhine phylogeny.
Roos, C., Schmitz, J., & Zischler, H. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403852101 · Cited by 262 · see citing works
Strong mitochondrial DNA support for a Cretaceous origin of modern avian lineages
Brown, J. W., Rest, J. S., García-Moreno, J., Sorenson, M. D., & Mindell, D. P. (2008) · BMC Biology · doi:10.1186/1741-7007-6-6 · Cited by 236 · see citing works
Ho, S. Y. W. (2005) · Molecular Biology and Evolution · doi:10.1093/molbev/msi125 · Cited by 190 · see citing works
Roger, A. J., & Hug, L. A. (2006) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2006.1845 · Cited by 180 · see citing works
Rates of phenotypic and genomic evolution during the Cambrian explosion
Lee, M. S. Y., Soubrier, J., & Edgecombe, G. D. (2013) · Current Biology · doi:10.1016/j.cub.2013.07.055 · Cited by 162 · see citing works
The impact of fossils and taxon sampling on ancient molecular dating analyses
Hug, L. A., & Roger, A. J. (2007) · Molecular Biology and Evolution · doi:10.1093/molbev/msm115 · Cited by 144 · see citing works
Molecular Clocks Do Not Support the Cambrian Explosion
Blair, J. E., & Hedges, S. B. (2005) · Molecular Biology and Evolution · doi:10.1093/molbev/msi039 · Cited by 73 · see citing works
Chernikova, D., Motamedi, S., Csürös, M., Koonin, E. V., & Rogozin, I. B. (2011) · Biology Direct · doi:10.1186/1745-6150-6-26 · Cited by 72 · see citing works
Sharpe*, S. C., Eme*, L., Brown, M. W., & Roger, A. J. (2015) · Advances in Marine Genomics · doi:10.1007/978-94-017-9642-2_1 · Cited by 49 · see citing works
- Authors
- Sanderson, M. J.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Sanderson, Michael J.
- Venue
- Bioinformatics
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-01-22
- Volume
- 19
- Issue
- 2
- Pages
- 301-302
- ISSN
- 1367-4803 (ISSN-L)
- 1367-4811
- OpenAlex
- W2159368494
- Cited by
- 1,906
- References
- 9
- Citations by year
- 2026: 67 · 2025: 99 · 2024: 104 · 2023: 86 · 2022: 116 · 2021: 84 · 2020: 80 · 2019: 61 · 2018: 58 · 2017: 49 · 2016: 68 · 2015: 61 · 2014: 77 · 2013: 85 · 2012: 86
- FWCI
- 22.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bioinformatics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Physical Sciences › Earth and Planetary Sciences › Paleontology › Evolution and Paleontology Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- R8, divergence time estimation, substitution rate estimation, relaxed molecular clock, fossil calibration, phylogenetics, bound-constrained optimization
- MeSH terms
- Algorithms, Database Management Systems, Phylogeny, Software, Time Factors, Genetic Variation, Sequence Analysis, DNA, Evolution, Molecular, Databases, Genetic, Genetic Drift
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
