Dna early from hominids human mitochondrial tracking

We estimated a split time between Homo neanderthalensis and H. Considering the widely held view that H. The Boxgrove tibia from Sussex, England , attributed to H. This estimation rather places a conservative upper bound of 93 ka for the time of the last major gene exchange between non-African and sub-Saharan African populations.

Mitochondrial DNA Clarifies Human Evolution by Max Ingman

As pointed out by Fu, Mittnik, et al. Finally, our results also allowed us to check whether the coalescence dates of some major haplogroups associated with human migrations table 2 are consistent with the archaeological evidence supplementary appendix S However, in the case of the Canary Islands, Remote Oceania, New Zealand, and the Americas, the estimated coalescence times were systematically older than the archaeological evidence. Potential explanations for such discrepancies include ancestral polymorphism in the founding population or complex demographic histories involving multiples waves of colonists.

N ote. In conclusion, our results demonstrate that the recent availability of ancient high-quality mtDNA genomes offers a powerful tool to robustly date past evolutionary events of our own species. Using the age of ancient sequences leads to far more reproducible inferences and allows circumventing the large number of assumptions behind node and root calibration, which in turn should lead to an improvement of the estimation of human mitochondrial substitution rates.

It should be possible to obtain increasingly narrow and precise substitution rate estimates by including additional ancient genomes in the analyses, as they will become available. In this context, ancient isolates from geographic regions which are not represented yet, such as Africa and Australia, would be particularly helpful, as these would allow fine calibration of further clades in the human mitochondrial genome. From a more general point of view, the growing availability of ancient sequences due to sequencing technology improvements should allow reliable tip-calibrated phylogenetic rate and divergence time estimates to be obtained in many species for which internal nodes split times information are presently not available.

Our data set composed of cAMH and 30 ancient human complete mitochondrial genomes, consisting of both new and publicly available sequences. A total of new samples were obtained from two different sources. First, samples were selected by randomly choosing two individuals from each of the 51 populations of the HGDP-CEPH human genome diversity cell line panel Cann et al.

Second, we randomly selected two individuals from each of the 21 Native American and one Siberian populations that had previously been genotyped at autosomal microsatellites Wang et al. Details on the molecular and data processing are given in supplementary appendix S1 , Supplementary Material online. A total of public cAMH sequences were selected from GenBank to complete the geographic coverage and the haplogroup spectrum of the cAMH sequences generated in this project supplementary appendix S2 , Supplementary Material online.

A chimpanzee sequence accession number HM was used as outgroup. This resulted in a 16,bp aligned sequences matrix in which each nucleotide has been annotated by matching to the Cambridge reference annotation file using an in-house R script R Core Team It is well documented that substantial chemical modifications of nucleotide bases can be introduced postmortem as a result of DNA damage Paabo ; Sawyer et al. This feature has been used to distinguish between ancient damaged sequences and putative modern contaminants Green et al.

Here, we took advantage of the random nature of DNA damage to test for sequence quality in the ancient samples. Moreover, given that deamination errors are expected to happen at random, the probability of observing the same error in multiple sequences is low. The optimal partitioning scheme and the best-fit nucleotide substitution model for each partition of the mtDNA molecule was estimated using the software PartitionFinder Lanfear et al.

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We defined the following seven groups of nucleotides: 1 HVS1, 2 HVS2, 3, 4, 5 protein coding positions at 1st, 2nd, and 3rd codon, 6 tRNAs, 7 rRNAs and used PartitionFinder to analyze every scheme that includes those seven groups in any possible combination. We also used the same algorithm to independently select the best model of nucleotide evolution to apply to the whole molecule. In all analyses on the partitioned data, substitution and clock models were unlinked, whereas tree topology was assumed to be the same between schemes.

We also performed separate phylogenetic inferences on the whole-mtDNA molecule. We compared constant size, logistic growth, and exponential growth models. We specified a model where the probability that any transition sites of the alignment remained undamaged is assumed to decay exponentially with sample age. Model choice was based on the Bayes factors calculated from the marginal likelihoods, the latter being computed using both the PS and SS methods as recently recommended by Baele et al.


Substitution models were based on the best fit from Partition Finder, and rate variation among sites both including and excluding invariant sites was modeled with a discrete gamma distribution with four rate categories. An independent constant population size model was applied to the Neanderthal clade as recommended by Briggs et al. For each analysis, we ran four independent chains in which samples were drawn every 5, MCMC steps from a total of 50,, steps, after a discarded burn-in of 5,, steps. Parameter estimation was based on the samples combined from the different chains. The best supported tree was estimated from the combined samples using the maximum clade credibility method implemented in TreeAnnotator.

We compared the effect of different tree calibration strategies on the estimation of substitution rates and divergence times. Priors were placed on tips, internal nodes, and root age.

Mitochondrial Eve

Tip age was specified using reliable dates available for all high-quality ancient complete human mtDNA sequences available at the time. Uncertainty around the dating was modeled in BEAST using a normal prior with standard deviation equal to the standard error of the radiocarbon date supplementary appendix S3 , Supplementary Material online. We first used date-randomization tests to determine whether the temporal and genetic information contained in the ancient sequences were sufficient for a thorough estimation of substitution rates.

From the total data set composed of sequences , ages of the sequences were randomly shuffled ten times, and date-randomized data sets were reanalyzed with BEAST. Point-calibrated tips analyses i. To prevent the chain from becoming stuck on unrealistic inflated values, flat priors uniform distributions were applied for all other internal nodes and root ages 0. Tip dating analyses were performed while considering aAMHs intraspecific calibration and archaic humans extra-specific calibration either separately or simultaneously. Finally, to test whether the inferred substitution rates are dependent on a single-dated aAMH sequence, we performed BEAST analyses using each ancient mtDNA sequence independently as separate tip calibrations.

Internal node calibration was conducted by specifying priors on the ages of some specific nodes in the tree. To avoid as much as possible any subjective bias, we enforced the following three criteria: 1 the anthropological evidence must correspond to a discrete expansion or migration, 2 at least one candidate haplotype has to be associated with the demographic event, and 3 the age of the event needs to be based on solid archaeological evidence.

We could identify ten different events which fitted all our criteria: The colonization of Sahul, Europe, Japan, America, Sardinia, Remote Oceania, Canary Islands, Madagascar, New Zealand, and the post glacial re-expansion of populations from the Franco-Iberian refuge areas see supplementary appendix S4 , Supplementary Material online, for details. Analyses were run considering all ten internal nodes either simultaneously or independently.

These values were chosen for consistency with previous studies and information from the fossil record Benton and Donoghue Equal amounts of computational time number of MCMC iterations and independent chains as previously given were employed for the different calibration scenarios.

We also selected an equal number of posterior samples to estimate parameters and the marginal likelihood. Secondly, we investigated whether the calibration scenario had an influence on the tree topology. To do so, it is necessary to control for the MCMC error in the best supported topology that can be inferred among independent BEAST runs performed assuming the same calibration approach. Topological distances between pairs of trees calculated on a sample of ten independent trees inferred per calibration scenario were generated using the Penny and Hendy statistic Penny and Hendy , which is defined as twice the number of internal branches defining different bipartitions of the tips.

To be comparable between all scenarios, trees were pruned to contain AMH tips only. We tested for deviations from a strict molecular clock by considering the standard deviation of the uncorrelated log-normal relaxed clock the parameter ucld. If this parameter is small close to 0 , there is little variation in rates among branches, and the data are clock like. If this parameter takes values greater than 1 then the standard deviation in branch rates is greater than the mean rate, and the data exhibit substantial rate heterogeneity among lineages.

We also empirically investigated the effect of the chimpanzee and archaic human sequences on rate heterogeneity among lineages. To do so, we ran two analyses using alignments excluding those sequences one excluding the chimpanzee only and one excluding both the chimpanzee and Neanderthal sequences and performed model comparison through the evaluation of Bayes factors, as described previously. The authors thank Mark Stoneking for generating the sequence data in his laboratory.

They thank Mattias Jakobsson, Morten Rasmussen, Eske Willerslev, Maanasa Raghavan, and Michael Knapp for providing us access to sequence data and associated information in advance of their publication.

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  8. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Advanced Search. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents. Materials and Methods. Oxford Academic. Google Scholar.

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    Anders Eriksson. Mingkun Li. Benjamin Sobkowiak.

    Lucy A. Vera Warmuth. Andres Ruiz-Linares. Andrea Manica. Associate editor: Beth Shapiro. The sequences reported in this article have been deposited in the GenBank under the accession nos.

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    Cite Citation. Permissions Icon Permissions. Abstract Reliable estimates of the rate at which DNA accumulates mutations the substitution rate are crucial for our understanding of the evolution and past demography of virtually any species. Bayesian phylogenetic inference , mitochondrial substitution rates , divergence times , human , calibration strategy , ancient genomes , molecular clock. Open in new tab Download slide. Table 1.

    Ancient DNA and the New Science of the Human Past

    Open in new tab. Table 2. MtDNA variation predicts population size in humans and reveals a major southern Asian chapter in human prehistory.