Publications by authors named "Gabriel Renaud"

47 Publications

Population genomics of the Viking world.

Nature 2020 09 16;585(7825):390-396. Epub 2020 Sep 16.

NTNU University Museum, Department of Archaeology and Cultural History, Trondheim, Norway.

The maritime expansion of Scandinavian populations during the Viking Age (about AD 750-1050) was a far-flung transformation in world history. Here we sequenced the genomes of 442 humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past millennium, and trace positively selected loci-including the lactase-persistence allele of LCT and alleles of ANKA that are associated with the immune response-in detail. We conclude that the Viking diaspora was characterized by substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased contact with the rest of the continent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-2688-8DOI Listing
September 2020

The repertoire of family A-peptide GPCRs in archaic hominins.

Peptides 2019 12 24;122:170154. Epub 2019 Sep 24.

Laboratoire Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), Université de Toulouse, CNRS, UPS, Toulouse, France. Electronic address:

Given the importance of G-protein coupled receptors in the regulation of many physiological functions, deciphering the relationships between genotype and phenotype in past and present hominin GPCRs is of main interest to understand the evolutionary process that contributed to the present-day variability in human traits and health. Here, we carefully examined the publicly available genomic and protein sequence databases of the archaic hominins (Neanderthal and Denisova) to draw up the catalog of coding variations in GPCRs for peptide ligands, in comparison with living humans. We then searched in the literature the functional changes, phenotypes and risk of disease possibly associated with the detected variants. Our survey suggests that Neanderthal and Denisovan hominins were likely prone to lower risk of obesity, to enhanced platelet aggregation in response to thrombin, to better response to infection, to less anxiety and aggressiveness and to favorable sociability. While some archaic variants were likely advantageous in the past, they might be responsible for maladaptive disorders today in the context of modern life and/or specific regional distribution. For example, an archaic haplotype in the neuromedin receptor 2 is susceptible to confer risk of diabetic nephropathy in type 1 diabetes in present-day Europeans. Paying attention to the pharmacological properties of some of the archaic variants described in this study may be helpful to understand the variability of therapeutic efficacy between individuals or ethnic groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.peptides.2019.170154DOI Listing
December 2019

A likelihood method for estimating present-day human contamination in ancient male samples using low-depth X-chromosome data.

Bioinformatics 2020 02;36(3):828-841

Department of Computational Biology, University of Lausanne, 1015 Lausanne, Switzerland.

Motivation: The presence of present-day human contaminating DNA fragments is one of the challenges defining ancient DNA (aDNA) research. This is especially relevant to the ancient human DNA field where it is difficult to distinguish endogenous molecules from human contaminants due to their genetic similarity. Recently, with the advent of high-throughput sequencing and new aDNA protocols, hundreds of ancient human genomes have become available. Contamination in those genomes has been measured with computational methods often developed specifically for these empirical studies. Consequently, some of these methods have not been implemented and tested for general use while few are aimed at low-depth nuclear data, a common feature in aDNA datasets.

Results: We develop a new X-chromosome-based maximum likelihood method for estimating present-day human contamination in low-depth sequencing data from male individuals. We implement our method for general use, assess its performance under conditions typical of ancient human DNA research, and compare it to previous nuclear data-based methods through extensive simulations. For low-depth data, we show that existing methods can produce unusable estimates or substantially underestimate contamination. In contrast, our method provides accurate estimates for a depth of coverage as low as 0.5× on the X-chromosome when contamination is below 25%. Moreover, our method still yields meaningful estimates in very challenging situations, i.e. when the contaminant and the target come from closely related populations or with increased error rates. With a running time below 5 min, our method is applicable to large scale aDNA genomic studies.

Availability And Implementation: The method is implemented in C++ and R and is available in github.com/sapfo/contaminationX and popgen.dk/angsd.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/btz660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215924PMC
February 2020

The population history of northeastern Siberia since the Pleistocene.

Nature 2019 06 5;570(7760):182-188. Epub 2019 Jun 5.

Institute of Archaeology and Ethnography of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.

Northeastern Siberia has been inhabited by humans for more than 40,000 years but its deep population history remains poorly understood. Here we investigate the late Pleistocene population history of northeastern Siberia through analyses of 34 newly recovered ancient genomes that date to between 31,000 and 600 years ago. We document complex population dynamics during this period, including at least three major migration events: an initial peopling by a previously unknown Palaeolithic population of 'Ancient North Siberians' who are distantly related to early West Eurasian hunter-gatherers; the arrival of East Asian-related peoples, which gave rise to 'Ancient Palaeo-Siberians' who are closely related to contemporary communities from far-northeastern Siberia (such as the Koryaks), as well as Native Americans; and a Holocene migration of other East Asian-related peoples, who we name 'Neo-Siberians', and from whom many contemporary Siberians are descended. Each of these population expansions largely replaced the earlier inhabitants, and ultimately generated the mosaic genetic make-up of contemporary peoples who inhabit a vast area across northern Eurasia and the Americas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-019-1279-zDOI Listing
June 2019

Joint Estimates of Heterozygosity and Runs of Homozygosity for Modern and Ancient Samples.

Genetics 2019 07 14;212(3):587-614. Epub 2019 May 14.

Lundbeck Foundation GeoGenetics Center, Globe Institute, University of Copenhagen, 1350K, Denmark.

Both the total amount and the distribution of heterozygous sites within individual genomes are informative about the genetic diversity of the population they belong to. Detecting true heterozygous sites in ancient genomes is complicated by the generally limited coverage achieved and the presence of post-mortem damage inflating sequencing errors. Additionally, large runs of homozygosity found in the genomes of particularly inbred individuals and of domestic animals can skew estimates of genome-wide heterozygosity rates. Current computational tools aimed at estimating runs of homozygosity and genome-wide heterozygosity levels are generally sensitive to such limitations. Here, we introduce ROHan, a probabilistic method which substantially improves the estimate of heterozygosity rates both genome-wide and for genomic local windows. It combines a local Bayesian model and a Hidden Markov Model at the genome-wide level and can work both on modern and ancient samples. We show that our algorithm outperforms currently available methods for predicting heterozygosity rates for ancient samples. Specifically, ROHan can delineate large runs of homozygosity (at megabase scales) and produce a reliable confidence interval for the genome-wide rate of heterozygosity outside of such regions from modern genomes with a depth of coverage as low as 5-6× and down to 7-8× for ancient samples showing moderate DNA damage. We apply ROHan to a series of modern and ancient genomes previously published and revise available estimates of heterozygosity for humans, chimpanzees and horses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1534/genetics.119.302057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614887PMC
July 2019

DamMet: ancient methylome mapping accounting for errors, true variants, and post-mortem DNA damage.

Gigascience 2019 04;8(4)

Lundbeck Foundation GeoGenetics Center, University of Copenhagen, Øster Voldgade 5-7, 1350K Copenhagen, Denmark.

Background: Recent computational advances in ancient DNA research have opened access to the detection of ancient DNA methylation footprints at the genome-wide scale. The most commonly used approach infers the methylation state of a given genomic region on the basis of the amount of nucleotide mis-incorporations observed at CpG dinucleotide sites. However, this approach overlooks a number of confounding factors, including the presence of sequencing errors and true variants. The scale and distribution of the inferred methylation measurements are also variable across samples, precluding direct comparisons.

Findings: Here, we present DamMet, an open-source software program retrieving maximum likelihood estimates of regional CpG methylation levels from ancient DNA sequencing data. It builds on a novel statistical model of post-mortem DNA damage for dinucleotides, accounting for sequencing errors, genotypes, and differential post-mortem cytosine deamination rates at both methylated and unmethylated sites. To validate DamMet, we extended gargammel, a sequence simulator for ancient DNA data, by introducing methylation-dependent features of post-mortem DNA decay. This new simulator provides direct validation of DamMet predictions. Additionally, the methylation levels inferred by DamMet were found to be correlated to those inferred by epiPALEOMIX and both on par and directly comparable to those measured from whole-genome bisulphite sequencing experiments of fresh tissues.

Conclusions: DamMet provides genuine estimates for local DNA methylation levels in ancient individual genomes. The returned estimates are directly cross-sample comparable, and the software is available as an open-source C++ program hosted at https://gitlab.com/KHanghoj/DamMet along with a manual and tutorial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gigascience/giz025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474913PMC
April 2019

Authentication and Assessment of Contamination in Ancient DNA.

Methods Mol Biol 2019 ;1963:163-194

Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen K, Denmark.

Contamination from both present-day humans and postmortem microbial sources is a common challenge in ancient DNA studies. Here we present a suite of tools to assist in the assessment of contamination in ancient DNA data sets. These tools perform standard tests of authenticity of ancient DNA data including detecting the presence of postmortem damage signatures in sequence alignments and quantifying the amount of present-day human contamination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-4939-9176-1_17DOI Listing
September 2019

Author Correction: 137 ancient human genomes from across the Eurasian steppes.

Nature 2018 11;563(7729):E16

Buketov Karaganda State University, Saryarka Archaeological Institute, Karaganda, Kazakhstan.

with In this Article, Angela M. Taravella and Melissa A. Wilson Sayres have been added to the author list (associated with: School of Life Sciences, Center for Evolution and Medicine, The Biodesign Institute, Arizona State University, Tempe, AZ, USA). The author list and Author Information section have been corrected online.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-018-0488-1DOI Listing
November 2018

137 ancient human genomes from across the Eurasian steppes.

Nature 2018 05 9;557(7705):369-374. Epub 2018 May 9.

Buketov Karaganda State University, Saryarka Archaeological Institute, Karaganda, Kazakhstan.

For thousands of years the Eurasian steppes have been a centre of human migrations and cultural change. Here we sequence the genomes of 137 ancient humans (about 1× average coverage), covering a period of 4,000 years, to understand the population history of the Eurasian steppes after the Bronze Age migrations. We find that the genetics of the Scythian groups that dominated the Eurasian steppes throughout the Iron Age were highly structured, with diverse origins comprising Late Bronze Age herders, European farmers and southern Siberian hunter-gatherers. Later, Scythians admixed with the eastern steppe nomads who formed the Xiongnu confederations, and moved westward in about the second or third century BC, forming the Hun traditions in the fourth-fifth century AD, and carrying with them plague that was basal to the Justinian plague. These nomads were further admixed with East Asian groups during several short-term khanates in the Medieval period. These historical events transformed the Eurasian steppes from being inhabited by Indo-European speakers of largely West Eurasian ancestry to the mostly Turkic-speaking groups of the present day, who are primarily of East Asian ancestry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-018-0094-2DOI Listing
May 2018

Improved de novo genomic assembly for the domestic donkey.

Sci Adv 2018 04 4;4(4):eaaq0392. Epub 2018 Apr 4.

Centre for GeoGenetics, Natural History Museum of Denmark, Øster Voldgade 5-7, 1350K Copenhagen, Denmark.

Donkeys and horses share a common ancestor dating back to about 4 million years ago. Although a high-quality genome assembly at the chromosomal level is available for the horse, current assemblies available for the donkey are limited to moderately sized scaffolds. The absence of a better-quality assembly for the donkey has hampered studies involving the characterization of patterns of genetic variation at the genome-wide scale. These range from the application of genomic tools to selective breeding and conservation to the more fundamental characterization of the genomic loci underlying speciation and domestication. We present a new high-quality donkey genome assembly obtained using the Chicago HiRise assembly technology, providing scaffolds of subchromosomal size. We make use of this new assembly to obtain more accurate measures of heterozygosity for equine species other than the horse, both genome-wide and locally, and to detect runs of homozygosity potentially pertaining to positive selection in domestic donkeys. Finally, this new assembly allowed us to identify fine-scale chromosomal rearrangements between the horse and the donkey that likely played an active role in their divergence and, ultimately, speciation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.aaq0392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938232PMC
April 2018

Origins and genetic legacies of the Caribbean Taino.

Proc Natl Acad Sci U S A 2018 03 20;115(10):2341-2346. Epub 2018 Feb 20.

Center for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen, Denmark;

The Caribbean was one of the last parts of the Americas to be settled by humans, but how and when the islands were first occupied remains a matter of debate. Ancient DNA can help answering these questions, but the work has been hampered by poor DNA preservation. We report the genome sequence of a 1,000-year-old Lucayan Taino individual recovered from the site of Preacher's Cave in the Bahamas. We sequenced her genome to 12.4-fold coverage and show that she is genetically most closely related to present-day Arawakan speakers from northern South America, suggesting that the ancestors of the Lucayans originated there. Further, we find no evidence for recent inbreeding or isolation in the ancient genome, suggesting that the Lucayans had a relatively large effective population size. Finally, we show that the native American components in some present-day Caribbean genomes are closely related to the ancient Taino, demonstrating an element of continuity between precontact populations and present-day Latino populations in the Caribbean.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1716839115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877975PMC
March 2018

glactools: a command-line toolset for the management of genotype likelihoods and allele counts.

Authors:
Gabriel Renaud

Bioinformatics 2018 04;34(8):1398-1400

Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig 04103, Germany.

Motivation: Research projects involving population genomics routinely need to store genotyping information, population allele counts, combine files from different samples, query the data and export it to various formats. This is often done using bespoke in-house scripts, which cannot be easily adapted to new projects and seldom constitute reproducible workflows.

Results: We introduce glactools, a set of command-line utilities that can import data from genotypes or population-wide allele counts into an intermediate representation, compute various operations on it and export the data to several file formats used by population genetics software. This intermediate format can take two forms, one to store per-individual genotype likelihoods and a second for allele counts from one or more individuals. glactools allows users to perform operations such as intersecting datasets, merging individuals into populations, creating subsets, perform queries (e.g. return sites where a given population does not share an allele with a second one) and compute summary statistics to answer biologically relevant questions.

Availability And Implementation: glactools is freely available for use under the GPL. It requires a C ++ compiler and the htslib library. The source code and the instructions about how to download test data are available on the website (https://grenaud.github.io/glactools/).

Contact: [email protected]

Supplementary Information: Supplementary data are available at Bioinformatics online.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/btx749DOI Listing
April 2018

Genetic Discontinuity between the Maritime Archaic and Beothuk Populations in Newfoundland, Canada.

Curr Biol 2017 Oct 12;27(20):3149-3156.e11. Epub 2017 Oct 12.

McMaster Ancient DNA Centre, Department of Anthropology, McMaster University, Hamilton, ON L8S 4L8, Canada; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4L8, Canada; Humans & the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1Z8, Canada. Electronic address:

Situated at the furthest northeastern edge of Canada, the island of Newfoundland (approximately 110,000 km) and Labrador (approximately 295,000 km) today constitute a province characterized by abundant natural resources but low population density. Both landmasses were covered by the Laurentide ice sheet during the Last Glacial Maximum (18,000 years before present [YBP]); after the glacier retreated, ice patches remained on the island until ca. 9,000 calibrated (cal) YBP [1]. Nevertheless, indigenous peoples, whose ancestors had trekked some 5,000 km from the west coast, arrived approximately 10,000 cal YBP in Labrador and ca. 6,000 cal YBP in Newfoundland [2, 3]. Differential features in material culture indicate at least three settlement episodes by distinct cultural groups, including the Maritime Archaic, Palaeoeskimo, and Beothuk. Newfoundland has remained home to indigenous peoples until present day with only one apparent hiatus (3,400-2,800 YBP). This record suggests abandonment, severe constriction, or local extinction followed by subsequent immigrations from single or multiple source populations, but the specific dynamics and the cultural and biological relationships, if any, among these successive peoples remain enigmatic [4]. By examining the mitochondrial genome diversity and isotopic ratios of 74 ancient remains in conjunction with the archaeological record, we have provided definitive evidence for the genetic discontinuity between the maternal lineages of these populations. This northeastern margin of North America appears to have been populated multiple times by distinct groups that did not share a recent common ancestry, but rather one much deeper in time at the entry point into the continent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cub.2017.08.053DOI Listing
October 2017

Ancient genomes show social and reproductive behavior of early Upper Paleolithic foragers.

Science 2017 11 5;358(6363):659-662. Epub 2017 Oct 5.

Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen, Denmark.

Present-day hunter-gatherers (HGs) live in multilevel social groups essential to sustain a population structure characterized by limited levels of within-band relatedness and inbreeding. When these wider social networks evolved among HGs is unknown. To investigate whether the contemporary HG strategy was already present in the Upper Paleolithic, we used complete genome sequences from Sunghir, a site dated to ~34,000 years before the present, containing multiple anatomically modern human individuals. We show that individuals at Sunghir derive from a population of small effective size, with limited kinship and levels of inbreeding similar to HG populations. Our findings suggest that Upper Paleolithic social organization was similar to that of living HGs, with limited relatedness within residential groups embedded in a larger mating network.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.aao1807DOI Listing
November 2017

A fourth Denisovan individual.

Sci Adv 2017 07 7;3(7):e1700186. Epub 2017 Jul 7.

Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany.

The presence of Neandertals in Europe and Western Eurasia before the arrival of anatomically modern humans is well supported by archaeological and paleontological data. In contrast, fossil evidence for Denisovans, a sister group of Neandertals recently identified on the basis of DNA sequences, is limited to three specimens, all of which originate from Denisova Cave in the Altai Mountains (Siberia, Russia). We report the retrieval of DNA from a deciduous lower second molar (), discovered in a deep stratigraphic layer in Denisova Cave, and show that this tooth comes from a female Denisovan individual. On the basis of the number of "missing substitutions" in the mitochondrial DNA determined from the specimen, we find that is substantially older than two of the other Denisovans, reinforcing the view that Denisovans were likely to have been present in the vicinity of Denisova Cave over an extended time period. We show that the level of nuclear DNA sequence diversity found among Denisovans is within the lower range of that of present-day human populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.1700186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501502PMC
July 2017

Correction: Joint Estimation of Contamination, Error and Demography for Nuclear DNA from Ancient Humans.

PLoS Genet 2016 Nov 8;12(11):e1006444. Epub 2016 Nov 8.

[This corrects the article DOI: 10.1371/journal.pgen.1005972.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1006444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100944PMC
November 2016

gargammel: a sequence simulator for ancient DNA.

Bioinformatics 2017 02;33(4):577-579

Center for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350K Copenhagen, Denmark.

Summary: Ancient DNA has emerged as a remarkable tool to infer the history of extinct species and past populations. However, many of its characteristics, such as extensive fragmentation, damage and contamination, can influence downstream analyses. To help investigators measure how these could impact their analyses in silico , we have developed gargammel, a package that simulates ancient DNA fragments given a set of known reference genomes. Our package simulates the entire molecular process from post-mortem DNA fragmentation and DNA damage to experimental sequencing errors, and reproduces most common bias observed in ancient DNA datasets.

Availability And Implementation: The package is publicly available on github: https://grenaud.github.io/gargammel/ and released under the GPL.

Contact: [email protected]

Supplementary Information: Supplementary data are available at Bioinformatics online.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/btw670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408798PMC
February 2017

The Simons Genome Diversity Project: 300 genomes from 142 diverse populations.

Nature 2016 Oct 21;538(7624):201-206. Epub 2016 Sep 21.

Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.

Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature18964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161557PMC
October 2016

Joint Estimation of Contamination, Error and Demography for Nuclear DNA from Ancient Humans.

PLoS Genet 2016 Apr 6;12(4):e1005972. Epub 2016 Apr 6.

Department of Integrative Biology, University of California, Berkeley, Berkeley, California, United States of America.

When sequencing an ancient DNA sample from a hominin fossil, DNA from present-day humans involved in excavation and extraction will be sequenced along with the endogenous material. This type of contamination is problematic for downstream analyses as it will introduce a bias towards the population of the contaminating individual(s). Quantifying the extent of contamination is a crucial step as it allows researchers to account for possible biases that may arise in downstream genetic analyses. Here, we present an MCMC algorithm to co-estimate the contamination rate, sequencing error rate and demographic parameters-including drift times and admixture rates-for an ancient nuclear genome obtained from human remains, when the putative contaminating DNA comes from present-day humans. We assume we have a large panel representing the putative contaminant population (e.g. European, East Asian or African). The method is implemented in a C++ program called 'Demographic Inference with Contamination and Error' (DICE). We applied it to simulations and genome data from ancient Neanderthals and modern humans. With reasonable levels of genome sequence coverage (>3X), we find we can recover accurate estimates of all these parameters, even when the contamination rate is as high as 50%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1005972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822957PMC
April 2016

Pleistocene Mitochondrial Genomes Suggest a Single Major Dispersal of Non-Africans and a Late Glacial Population Turnover in Europe.

Curr Biol 2016 Mar 4;26(6):827-33. Epub 2016 Feb 4.

Department of Geosciences, Biogeology, University of Tübingen, Hölderlinstraße 12, 72074 Tübingen, Germany; Senckenberg Centre for Human Evolution and Palaeoenvironment, University of Tübingen, 72072 Tübingen, Germany.

How modern humans dispersed into Eurasia and Australasia, including the number of separate expansions and their timings, is highly debated [1, 2]. Two categories of models are proposed for the dispersal of non-Africans: (1) single dispersal, i.e., a single major diffusion of modern humans across Eurasia and Australasia [3-5]; and (2) multiple dispersal, i.e., additional earlier population expansions that may have contributed to the genetic diversity of some present-day humans outside of Africa [6-9]. Many variants of these models focus largely on Asia and Australasia, neglecting human dispersal into Europe, thus explaining only a subset of the entire colonization process outside of Africa [3-5, 8, 9]. The genetic diversity of the first modern humans who spread into Europe during the Late Pleistocene and the impact of subsequent climatic events on their demography are largely unknown. Here we analyze 55 complete human mitochondrial genomes (mtDNAs) of hunter-gatherers spanning ∼35,000 years of European prehistory. We unexpectedly find mtDNA lineage M in individuals prior to the Last Glacial Maximum (LGM). This lineage is absent in contemporary Europeans, although it is found at high frequency in modern Asians, Australasians, and Native Americans. Dating the most recent common ancestor of each of the modern non-African mtDNA clades reveals their single, late, and rapid dispersal less than 55,000 years ago. Demographic modeling not only indicates an LGM genetic bottleneck, but also provides surprising evidence of a major population turnover in Europe around 14,500 years ago during the Late Glacial, a period of climatic instability at the end of the Pleistocene.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cub.2016.01.037DOI Listing
March 2016

Nuclear and mitochondrial DNA sequences from two Denisovan individuals.

Proc Natl Acad Sci U S A 2015 Dec 16;112(51):15696-700. Epub 2015 Nov 16.

Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany;

Denisovans, a sister group of Neandertals, have been described on the basis of a nuclear genome sequence from a finger phalanx (Denisova 3) found in Denisova Cave in the Altai Mountains. The only other Denisovan specimen described to date is a molar (Denisova 4) found at the same site. This tooth carries a mtDNA sequence similar to that of Denisova 3. Here we present nuclear DNA sequences from Denisova 4 and a morphological description, as well as mitochondrial and nuclear DNA sequence data, from another molar (Denisova 8) found in Denisova Cave in 2010. This new molar is similar to Denisova 4 in being very large and lacking traits typical of Neandertals and modern humans. Nuclear DNA sequences from the two molars form a clade with Denisova 3. The mtDNA of Denisova 8 is more diverged and has accumulated fewer substitutions than the mtDNAs of the other two specimens, suggesting Denisovans were present in the region over an extended period. The nuclear DNA sequence diversity among the three Denisovans is comparable to that among six Neandertals, but lower than that among present-day humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1519905112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697428PMC
December 2015

Schmutzi: estimation of contamination and endogenous mitochondrial consensus calling for ancient DNA.

Genome Biol 2015 Oct 12;16:224. Epub 2015 Oct 12.

Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, Leipzig, Germany.

Unlabelled: Ancient DNA is typically highly degraded with appreciable cytosine deamination, and contamination with present-day DNA often complicates the identification of endogenous molecules. Together, these factors impede accurate assembly of the endogenous ancient mitochondrial genome. We present schmutzi, an iterative approach to jointly estimate present-day human contamination in ancient human DNA datasets and reconstruct the endogenous mitochondrial genome. By using sequence deamination patterns and fragment length distributions, schmutzi accurately reconstructs the endogenous mitochondrial genome sequence even when contamination exceeds 50 %. Given sufficient coverage, schmutzi also produces reliable estimates of contamination across a range of contamination rates.

Availability: https://bioinf.eva.mpg.de/schmutzi/ license:GPLv3.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-015-0776-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601135PMC
October 2015

Kiwi genome provides insights into evolution of a nocturnal lifestyle.

Genome Biol 2015 Jul 23;16:147. Epub 2015 Jul 23.

Institute of Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, Leipzig, 04103, Germany.

Background: Kiwi, comprising five species from the genus Apteryx, are endangered, ground-dwelling bird species endemic to New Zealand. They are the smallest and only nocturnal representatives of the ratites. The timing of kiwi adaptation to a nocturnal niche and the genomic innovations, which shaped sensory systems and morphology to allow this adaptation, are not yet fully understood.

Results: We sequenced and assembled the brown kiwi genome to 150-fold coverage and annotated the genome using kiwi transcript data and non-redundant protein information from multiple bird species. We identified evolutionary sequence changes that underlie adaptation to nocturnality and estimated the onset time of these adaptations. Several opsin genes involved in color vision are inactivated in the kiwi. We date this inactivation to the Oligocene epoch, likely after the arrival of the ancestor of modern kiwi in New Zealand. Genome comparisons between kiwi and representatives of ratites, Galloanserae, and Neoaves, including nocturnal and song birds, show diversification of kiwi's odorant receptors repertoire, which may reflect an increased reliance on olfaction rather than sight during foraging. Further, there is an enrichment of genes influencing mitochondrial function and energy expenditure among genes that are rapidly evolving specifically on the kiwi branch, which may also be linked to its nocturnal lifestyle.

Conclusions: The genomic changes in kiwi vision and olfaction are consistent with changes that are hypothesized to occur during adaptation to nocturnal lifestyle in mammals. The kiwi genome provides a valuable genomic resource for future genome-wide comparative analyses to other extinct and extant diurnal ratites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-015-0711-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511969PMC
July 2015

deML: robust demultiplexing of Illumina sequences using a likelihood-based approach.

Bioinformatics 2015 Mar 30;31(5):770-2. Epub 2014 Oct 30.

Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Saxony D-04103, Germany.

Motivation: Pooling multiple samples increases the efficiency and lowers the cost of DNA sequencing. One approach to multiplexing is to use short DNA indices to uniquely identify each sample. After sequencing, reads must be assigned in silico to the sample of origin, a process referred to as demultiplexing. Demultiplexing software typically identifies the sample of origin using a fixed number of mismatches between the read index and a reference index set. This approach may fail or misassign reads when the sequencing quality of the indices is poor.

Results: We introduce deML, a maximum likelihood algorithm that demultiplexes Illumina sequences. deML computes the likelihood of an observed index sequence being derived from a specified sample. A quality score which reflects the probability of the assignment being correct is generated for each read. Using these quality scores, even very problematic datasets can be demultiplexed and an error threshold can be set.

Availability And Implementation: deML is freely available for use under the GPL (http://bioinf.eva.mpg.de/deml/).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/btu719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341068PMC
March 2015

trieFinder: an efficient program for annotating Digital Gene Expression (DGE) tags.

BMC Bioinformatics 2014 Oct 13;15:329. Epub 2014 Oct 13.

Translational and Functional Genomics Branch, Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-8004, USA.

Background: Quantification of a transcriptional profile is a useful way to evaluate the activity of a cell at a given point in time. Although RNA-Seq has revolutionized transcriptional profiling, the costs of RNA-Seq are still significantly higher than microarrays, and often the depth of data delivered from RNA-Seq is in excess of what is needed for simple transcript quantification. Digital Gene Expression (DGE) is a cost-effective, sequence-based approach for simple transcript quantification: by sequencing one read per molecule of RNA, this technique can be used to efficiently count transcripts while obviating the need for transcript-length normalization and reducing the total numbers of reads necessary for accurate quantification. Here, we present trieFinder, a program specifically designed to rapidly map, parse, and annotate DGE tags of various lengths against cDNA and/or genomic sequence databases.

Results: The trieFinder algorithm maps DGE tags in a two-step process. First, it scans FASTA files of RefSeq, UniGene, and genomic DNA sequences to create a database of all tags that can be derived from a predefined restriction site. Next, it compares the experimental DGE tags to this tag database, taking advantage of the fact that the tags are stored as a prefix tree, or "trie", which allows for linear-time searches for exact matches. DGE tags with mismatches are analyzed by recursive calls in the data structure. We find that, in terms of alignment speed, the mapping functionality of trieFinder compares favorably with Bowtie.

Conclusions: trieFinder can quickly provide the user an annotation of the DGE tags from three sources simultaneously, simplifying transcript quantification and novel transcript detection, delivering the data in a simple parsed format, obviating the need to post-process the alignment results. trieFinder is available at http://research.nhgri.nih.gov/software/trieFinder/.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2105-15-329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287429PMC
October 2014

Human paternal and maternal demographic histories: insights from high-resolution Y chromosome and mtDNA sequences.

Investig Genet 2014 24;5:13. Epub 2014 Sep 24.

Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, Leipzig D04103, Germany.

Background: Comparisons of maternally-inherited mitochondrial DNA (mtDNA) and paternally-inherited non-recombining Y chromosome (NRY) variation have provided important insights into the impact of sex-biased processes (such as migration, residence pattern, and so on) on human genetic variation. However, such comparisons have been limited by the different molecular methods typically used to assay mtDNA and NRY variation (for example, sequencing hypervariable segments of the control region for mtDNA vs. genotyping SNPs and/or STR loci for the NRY). Here, we report a simple capture array method to enrich Illumina sequencing libraries for approximately 500 kb of NRY sequence, which we use to generate NRY sequences from 623 males from 51 populations in the CEPH Human Genome Diversity Panel (HGDP). We also obtained complete mtDNA genome sequences from the same individuals, allowing us to compare maternal and paternal histories free of any ascertainment bias.

Results: We identified 2,228 SNPs in the NRY sequences and 2,163 SNPs in the mtDNA sequences. Our results confirm the controversial assertion that genetic differences between human populations on a global scale are bigger for the NRY than for mtDNA, although the differences are not as large as previously suggested. More importantly, we find substantial regional variation in patterns of mtDNA versus NRY variation. Model-based simulations indicate very small ancestral effective population sizes (<100) for the out-of-Africa migration as well as for many human populations. We also find that the ratio of female effective population size to male effective population size (Nf/Nm) has been greater than one throughout the history of modern humans, and has recently increased due to faster growth in Nf than Nm.

Conclusions: The NRY and mtDNA sequences provide new insights into the paternal and maternal histories of human populations, and the methods we introduce here should be widely applicable for further such studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/2041-2223-5-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4174254PMC
September 2014

Ancient human genomes suggest three ancestral populations for present-day Europeans.

Nature 2014 Sep;513(7518):409-13

Center for Global Health and Child Development, Kisumu 40100, Kenya.

We sequenced the genomes of a ∼7,000-year-old farmer from Germany and eight ∼8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had ∼44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature13673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170574PMC
September 2014

leeHom: adaptor trimming and merging for Illumina sequencing reads.

Nucleic Acids Res 2014 Oct 6;42(18):e141. Epub 2014 Aug 6.

Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany

The sequencing of libraries containing molecules shorter than the read length, such as in ancient or forensic applications, may result in the production of reads that include the adaptor, and in paired reads that overlap one another. Challenges for the processing of such reads are the accurate identification of the adaptor sequence and accurate reconstruction of the original sequence most likely to have given rise to the observed read(s). We introduce an algorithm that removes the adaptors and reconstructs the original DNA sequences using a Bayesian maximum a posteriori probability approach. Our algorithm is faster, and provides a more accurate reconstruction of the original sequence for both simulated and ancient DNA data sets, than other approaches. leeHom is released under the GPLv3 and is freely available from: https://bioinf.eva.mpg.de/leehom/
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gku699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191382PMC
October 2014

Patterns of coding variation in the complete exomes of three Neandertals.

Proc Natl Acad Sci U S A 2014 May 21;111(18):6666-71. Epub 2014 Apr 21.

Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany.

We present the DNA sequence of 17,367 protein-coding genes in two Neandertals from Spain and Croatia and analyze them together with the genome sequence recently determined from a Neandertal from southern Siberia. Comparisons with present-day humans from Africa, Europe, and Asia reveal that genetic diversity among Neandertals was remarkably low, and that they carried a higher proportion of amino acid-changing (nonsynonymous) alleles inferred to alter protein structure or function than present-day humans. Thus, Neandertals across Eurasia had a smaller long-term effective population than present-day humans. We also identify amino acid substitutions in Neandertals and present-day humans that may underlie phenotypic differences between the two groups. We find that genes involved in skeletal morphology have changed more in the lineage leading to Neandertals than in the ancestral lineage common to archaic and modern humans, whereas genes involved in behavior and pigmentation have changed more on the modern human lineage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1405138111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020111PMC
May 2014
-->