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      Using Phylogenomic Data to Explore the Effects of Relaxed Clocks and Calibration Strategies on Divergence Time Estimation: Primates as a Test Case

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          Abstract

          Primates have long been a test case for the development of phylogenetic methods for divergence time estimation. Despite a large number of studies, however, the timing of origination of crown Primates relative to the Cretaceous–Paleogene (K–Pg) boundary and the timing of diversification of the main crown groups remain controversial. Here, we analysed a data set of 372 taxa (367 Primates and 5 outgroups, 3.4 million aligned base pairs) that includes nine primate genomes. We systematically explore the effect of different interpretations of fossil calibrations and molecular clock models on primate divergence time estimates. We find that even small differences in the construction of fossil calibrations can have a noticeable impact on estimated divergence times, especially for the oldest nodes in the tree. Notably, choice of molecular rate model (autocorrelated or independently distributed rates) has an especially strong effect on estimated times, with the independent rates model producing considerably more ancient age estimates for the deeper nodes in the phylogeny. We implement thermodynamic integration, combined with Gaussian quadrature, in the program MCMCTree, and use it to calculate Bayes factors for clock models. Bayesian model selection indicates that the autocorrelated rates model fits the primate data substantially better, and we conclude that time estimates under this model should be preferred. We show that for eight core nodes in the phylogeny, uncertainty in time estimates is close to the theoretical limit imposed by fossil uncertainties. Thus, these estimates are unlikely to be improved by collecting additional molecular sequence data. All analyses place the origin of Primates close to the K–Pg boundary, either in the Cretaceous or straddling the boundary into the Palaeogene.

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          Dating of the human-ape splitting by a molecular clock of mitochondrial DNA.

          A new statistical method for estimating divergence dates of species from DNA sequence data by a molecular clock approach is developed. This method takes into account effectively the information contained in a set of DNA sequence data. The molecular clock of mitochondrial DNA (mtDNA) was calibrated by setting the date of divergence between primates and ungulates at the Cretaceous-Tertiary boundary (65 million years ago), when the extinction of dinosaurs occurred. A generalized least-squares method was applied in fitting a model to mtDNA sequence data, and the clock gave dates of 92.3 +/- 11.7, 13.3 +/- 1.5, 10.9 +/- 1.2, 3.7 +/- 0.6, and 2.7 +/- 0.6 million years ago (where the second of each pair of numbers is the standard deviation) for the separation of mouse, gibbon, orangutan, gorilla, and chimpanzee, respectively, from the line leading to humans. Although there is some uncertainty in the clock, this dating may pose a problem for the widely believed hypothesis that the pipedal creature Australopithecus afarensis, which lived some 3.7 million years ago at Laetoli in Tanzania and at Hadar in Ethiopia, was ancestral to man and evolved after the human-ape splitting. Another likelier possibility is that mtDNA was transferred through hybridization between a proto-human and a proto-chimpanzee after the former had developed bipedalism.
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            The delayed rise of present-day mammals.

            Did the end-Cretaceous mass extinction event, by eliminating non-avian dinosaurs and most of the existing fauna, trigger the evolutionary radiation of present-day mammals? Here we construct, date and analyse a species-level phylogeny of nearly all extant Mammalia to bring a new perspective to this question. Our analyses of how extant lineages accumulated through time show that net per-lineage diversification rates barely changed across the Cretaceous/Tertiary boundary. Instead, these rates spiked significantly with the origins of the currently recognized placental superorders and orders approximately 93 million years ago, before falling and remaining low until accelerating again throughout the Eocene and Oligocene epochs. Our results show that the phylogenetic 'fuses' leading to the explosion of extant placental orders are not only very much longer than suspected previously, but also challenge the hypothesis that the end-Cretaceous mass extinction event had a major, direct influence on the diversification of today's mammals.
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              Improving the accuracy of demographic and molecular clock model comparison while accommodating phylogenetic uncertainty.

              Recent developments in marginal likelihood estimation for model selection in the field of Bayesian phylogenetics and molecular evolution have emphasized the poor performance of the harmonic mean estimator (HME). Although these studies have shown the merits of new approaches applied to standard normally distributed examples and small real-world data sets, not much is currently known concerning the performance and computational issues of these methods when fitting complex evolutionary and population genetic models to empirical real-world data sets. Further, these approaches have not yet seen widespread application in the field due to the lack of implementations of these computationally demanding techniques in commonly used phylogenetic packages. We here investigate the performance of some of these new marginal likelihood estimators, specifically, path sampling (PS) and stepping-stone (SS) sampling for comparing models of demographic change and relaxed molecular clocks, using synthetic data and real-world examples for which unexpected inferences were made using the HME. Given the drastically increased computational demands of PS and SS sampling, we also investigate a posterior simulation-based analogue of Akaike's information criterion (AIC) through Markov chain Monte Carlo (MCMC), a model comparison approach that shares with the HME the appealing feature of having a low computational overhead over the original MCMC analysis. We confirm that the HME systematically overestimates the marginal likelihood and fails to yield reliable model classification and show that the AICM performs better and may be a useful initial evaluation of model choice but that it is also, to a lesser degree, unreliable. We show that PS and SS sampling substantially outperform these estimators and adjust the conclusions made concerning previous analyses for the three real-world data sets that we reanalyzed. The methods used in this article are now available in BEAST, a powerful user-friendly software package to perform Bayesian evolutionary analyses.
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                Author and article information

                Contributors
                Role: Associate Editor
                Journal
                Syst Biol
                Syst. Biol
                sysbio
                Systematic Biology
                Oxford University Press
                1063-5157
                1076-836X
                July 2018
                12 January 2018
                12 January 2018
                : 67
                : 4
                : 594-615
                Affiliations
                [1 ]School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK
                [2 ]Department of Genetics, Evolution and Environment, University College London, Gower Street, London WC1E 6BT, UK
                [3 ]Division of Fossil Primates, Duke University Lemur Center, Durham, 1013 Broad Street, NC 27705, USA
                [4 ]Department of Anthropology, The Ohio State University, Columbus, OH 43210, USA
                [5 ]Department of Biology, Duke University, Durham, NC 27708, USA
                Author notes
                Correspondence to be sent to: School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, UK Email: m.dosreisbarros@ 123456qmul.ac.uk .

                Deceased.

                Article
                syy001
                10.1093/sysbio/syy001
                6005039
                29342307
                469564e1-a0ba-4004-a3ba-bfcc814db698
                © The Author(s) 2018. Published by Oxford University Press, on behalf of the Society of Systematic Biologists.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For Permissions, please email: journals.permissions@ 123456oup.com

                History
                : 25 March 2017
                : 26 December 2017
                : 5 January 2018
                Page count
                Pages: 22
                Funding
                Funded by: National Science Foundation 10.13039/100000001
                Award ID: EF-0905606
                Funded by: Burroughs Wellcome Fund 10.13039/100000861
                Award ID: DEB-1354610
                Categories
                Regular Articles

                Animal science & Zoology
                bayes factors,bayesian analysis,fossil,molecular dating,phylogenomic analysis,primates,relaxed clock

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