Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Reconstructing the Human Past using Ancient and Modern Genomes
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The study of DNA variation is one of the most promising avenues for learning about the evolutionary and historical past of humans and other species. However, the difficulty associated with obtaining DNA directly from ancient remains have for long kept genomic studies of population history trapped in time; confined to interpreting patterns of modern-day variation without direct historical observations. In this thesis, I outline new approaches for the retrieval, analysis and interpretation of large-scale genomic data from ancient populations, including solutions to overcome problems associated with limited genome coverage, modern-day contamination, temporal differences between samples, and post-mortem DNA damage. I integrate large-scale genomic data sets from ancient remains with modern-day variation to trace the human past; from traits targeted by natural selection in the early ancestors of anatomically modern humans, to their descendants' interbreeding with archaic populations in Eurasia and the spread of agriculture in Europe and Africa. By first reconstructing the earliest population diversification events of early modern humans using a novel large-scale genomic data set from Khoe-San populations in southern Africa, I devise a new approach to search for genomic patterns of selective sweeps in ancestral populations and report evidence for skeletal development as a major target of selection during the emergence of early modern humans. Comparing publicly available genomes from archaic humans, I further find that the distribution of archaic human ancestry in Eurasia is more complex than previously thought. In the first direct genomic study of population structure in prehistoric populations, I demonstrate that individuals associated with farming- and hunter-gatherer complexes in Neolithic Scandinavia were strongly genetically differentiated, and direct comparisons with modern-day populations as well as other prehistoric individuals from Southern Europe suggest that this structure originated from Northward expansion of Neolithic farming populations. Finally, I develop a bioinformatic approach for removing modern-day contamination from large-scale ancient DNA sequencing data, and use this method to reconstruct the complete mitochondrial genome sequence of a Siberian Neandertal that is affected by substantial modern-day contamination.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. , 68 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1069
Keyword [en]
population genetics, paleogenomics, human evolution
National Category
Evolutionary Biology Genetics
Research subject
Evolutionary Genetics
Identifiers
URN: urn:nbn:se:uu:diva-206787ISBN: 978-91-554-8744-7 (print)OAI: oai:DiVA.org:uu-206787DiVA: diva2:645462
Public defence
2013-10-18, Zootissalen, Evolutionary Biology Centre, Norbyvägen 18C, Uppsala, 10:00 (English)
Opponent
Supervisors
Available from: 2013-09-27 Created: 2013-09-04 Last updated: 2014-01-23
List of papers
1. Genomic Variation in Seven Khoe-San Groups Reveals Adaptation and Complex African History
Open this publication in new window or tab >>Genomic Variation in Seven Khoe-San Groups Reveals Adaptation and Complex African History
Show others...
2012 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 338, no 6105, 374-379 p.Article in journal (Refereed) Published
Abstract [en]

The history of click-speaking Khoe-San, and African populations in general, remains poorly understood. We genotyped ∼2.3 million SNPs in 220 southern Africans and found that the Khoe-San diverged from other populations ≥100,000 years ago, but structure within the Khoe-San dated back to about 35,000 years ago. Genetic variation in various sub-Saharan populations did not localize the origin of modern humans to a single geographic region within Africa; instead, it indicated a history of admixture and stratification. We found evidence of adaptation targeting muscle function and immune response, potential adaptive introgression of UV-light protection, and selection predating modern human diversification involving skeletal and neurological development. These new findings illustrate the importance of African genomic diversity in understanding human evolutionary history.

National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-181302 (URN)10.1126/science.1227721 (DOI)000309955800039 ()
Available from: 2012-09-21 Created: 2012-09-21 Last updated: 2017-12-07
2. Archaic human ancestry in East Asia
Open this publication in new window or tab >>Archaic human ancestry in East Asia
2011 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 108, no 45, 18301-18306 p.Article in journal (Refereed) Published
Abstract [en]

Recent studies of ancient genomes have suggested that gene flow from archaic hominin groups to the ancestors of modern humans occurred on two separate occasions during the modern human expansion out of Africa. At the same time, decreasing levels of human genetic diversity have been found at increasing distance from Africa as a consequence of human expansion out of Africa. We analyzed the signal of archaic ancestry in modern human populations, and we investigated how serial founder models of human expansion affect the signal of archaic ancestry using simulations. For descendants of an archaic admixture event, we show that genetic drift coupled with ascertainment bias for common alleles can cause artificial but largely predictable differences in similarity to archaic genomes. In genotype data from non-Africans, this effect results in a biased genetic similarity to Neandertals with increasing distance from Africa. However, in addition to the previously reported gene flow between Neandertals and non-Africans as well as gene flow between an archaic human population from Siberia ("Denisovans") and Oceanians, we found a significant affinity between East Asians, particularly Southeast Asians, and the Denisovagenome-a pattern that is not expected under a model of solely Neandertal admixture in the ancestry of East Asians. These results suggest admixture between Denisovans or a Denisova-related population and the ancestors of East Asians, and that the history of anatomically modern and archaic humans might be more complex than previously proposed.

Keyword
human origins, ancient DNA
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-162448 (URN)10.1073/pnas.1108181108 (DOI)000296700000034 ()
Available from: 2011-12-01 Created: 2011-11-30 Last updated: 2017-12-08Bibliographically approved
3. Origins and Genetic Legacy of Neolithic Farmers and Hunter-Gatherers in Europe
Open this publication in new window or tab >>Origins and Genetic Legacy of Neolithic Farmers and Hunter-Gatherers in Europe
Show others...
2012 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 336, no 6080, 466-469 p.Article in journal (Refereed) Published
Abstract [en]

The farming way of life originated in the Near East some 11,000 years ago and had reached most of the European continent 5000 years later. However, the impact of the agricultural revolution on demography and patterns of genomic variation in Europe remains unknown. We obtained 249 million base pairs of genomic DNA from similar to 5000-year-old remains of three hunter-gatherers and one farmer excavated in Scandinavia and find that the farmer is genetically most similar to extant southern Europeans, contrasting sharply to the hunter-gatherers, whose distinct genetic signature is most similar to that of extant northern Europeans. Our results suggest that migration from southern Europe catalyzed the spread of agriculture and that admixture in the wake of this expansion eventually shaped the genomic landscape of modern-day Europe.

National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-174367 (URN)10.1126/science.1216304 (DOI)000303233400045 ()
Available from: 2012-05-24 Created: 2012-05-15 Last updated: 2017-12-07Bibliographically approved
4. Ancient genomes mirror mode of subsistence rather than geography in prehistoric Europe
Open this publication in new window or tab >>Ancient genomes mirror mode of subsistence rather than geography in prehistoric Europe
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Recent ancient DNA studies have provided new evidence for prehistoric population structure associated with the contentious transition to an agricultural lifestyle in Europe. In this study, we infer human population structure and history in Holocene Europe by generating ancient genomic sequence data from 9 Scandinavian individuals associated with the foraging Pitted Ware Culture and the agricultural Funnel Beaker Culture (TRB). We obtained up to 1.1x coverage of the genomes for the nine individuals allowing direct comparisons of the two groups. We show that the Neolithic Scandinavian individuals show remarkable population structure corresponding to their cultural association. Looking beyond Scandinavia, we integrate this data with ancient genomes from Southern Europe and find that the Tyrolean Iceman from an agricultural context is most similar to Scandinavian individuals from a farming context, whereas Mesolithic Iberian hunter-gatherers are most similar to Scandinavian hunter-gatherers, opposite to what would have been predicted from their geographical origins. This finding shows that among these individuals, lifestyle is the major determinant of genetic ancestry rather than geography. Comparisons with modern populations reveal a latitudinal relationship where Southern European populations such as Sardinians are closely related with the genetic variation of the agricultural groups, whereas hunter-gatherer individuals appear to have the closest relationship with Baltic populations such as Lithuanians and present-day Scandinavians. Our results also demonstrate that while Middle Eastern populations are not the most similar to Neolithic farmers, this observation can be explained by African-related admixture in more recent times for Middle Eastern groups, which, once accounted for, reveals that the other major component of their ancestry resembles Neolithic farmers. While present-day Scandinavian populations are intermediate between the two groups, consistent with admixture, they appear genetically slightly closer to Neolithic hunter-gatherers than Neolithic farmers. This suggests a model where initial colonization by agricultural populations was followed by later admixture with hunter-gatherer populations or gene flow from other regions.

National Category
Biological Sciences
Research subject
Evolutionary Genetics
Identifiers
urn:nbn:se:uu:diva-206770 (URN)
Available from: 2013-09-04 Created: 2013-09-04 Last updated: 2014-01-23
5. Separating endogenous ancient DNA from modern-day contamination: application to a Siberian Neandertal
Open this publication in new window or tab >>Separating endogenous ancient DNA from modern-day contamination: application to a Siberian Neandertal
Show others...
2014 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 111, no 6, 2229-2234 p.Article in journal (Refereed) Published
Abstract [en]

One of the main impediments for obtaining DNA sequences from ancient humanskeletons is the presence of contaminating modern human DNA molecules in many fossil samples and laboratory reagents. However, DNA fragments isolated from ancient specimens show a characteristic DNA damage pattern, caused by miscoding lesions, that differs from present-day DNA sequences. Here, we develop a framework for evaluating the likelihood of a sequence originating from a model with post-mortem degradation (PMD)—summarized in a PMD score—which allows the identification of DNA fragments that are unlikely to originate from present-day sources. We apply this approach to a contaminated Neandertal specimen from the Okladnikov cave in Siberia in order to isolate its endogenous DNA from modern human contaminants, and show that the reconstructed mitochondrial genome sequence is more closely related to the variation of Western Neandertals than what was discernible from previous analyses. Our method opens up the potential for genomic analysis of contaminated fossil material.

National Category
Biological Sciences
Research subject
Evolutionary Genetics
Identifiers
urn:nbn:se:uu:diva-206755 (URN)10.1073/pnas.1318934111 (DOI)000330999600045 ()
Available from: 2013-09-04 Created: 2013-09-04 Last updated: 2017-12-06Bibliographically approved
6. Investigating population history using temporal genetic differentiation
Open this publication in new window or tab >>Investigating population history using temporal genetic differentiation
Show others...
2014 (English)In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 31, no 9, 2516-2527 p.Article in journal (Refereed) Published
Abstract [en]

The rapid advance of sequencing technology coupled with improvements in molecular methods for obtaining genetic data from ancient sources holds the promise of producing a wealth of genomic data from time-separated individuals. However, the population genetic properties of time-structured samples have not been extensively explored. Here, we consider the implications of temporal sampling for analyses of genetic differentiation, and use a temporal coalescent framework to show that complex historical events such as size reductions, population replacements, and transient genetic barriers between populations leave a footprint of genetic differentiation that can be traced through history using temporal samples. Our results emphasize explicit consideration of the temporal structure when making inferences, and indicate that genomic data from ancient individuals will greatly increase our ability to reconstruct population history.

National Category
Biological Sciences
Research subject
Evolutionary Genetics
Identifiers
urn:nbn:se:uu:diva-206756 (URN)10.1093/molbev/msu192 (DOI)000343401100022 ()
Available from: 2013-09-04 Created: 2013-09-04 Last updated: 2017-12-06Bibliographically approved

Open Access in DiVA

fulltext(2056 kB)5221 downloads
File information
File name FULLTEXT01.pdfFile size 2056 kBChecksum SHA-512
ddcb32f58c218744b57b50b4f51193db5717e6727b95276728c03d12262d9a4ad384f2035318910e363e34fab60d3411cefecd5ea6cc37241e4f363c002ea2c0
Type fulltextMimetype application/pdf
Buy this publication >>

Authority records BETA

Skoglund, Pontus

Search in DiVA

By author/editor
Skoglund, Pontus
By organisation
Evolutionary Biology
Evolutionary BiologyGenetics

Search outside of DiVA

GoogleGoogle Scholar
Total: 5221 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 3073 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf