scholarly journals Model-based detection and analysis of introgressed Neanderthal ancestry in modern humans

2017 ◽  
Author(s):  
Matthias Steinrücken ◽  
Jeffrey P. Spence ◽  
John A. Kamm ◽  
Emilia Wieczorek ◽  
Yun S. Song
Keyword(s):  
Genetic Material ◽  
Genetic Load ◽  
Modern Human ◽  
Human Populations ◽  
Effective Population ◽  
Weak Selection ◽  
Modern Humans ◽  
High Coverage ◽  
Model Based ◽  
And Migration

AbstractGenetic evidence has revealed that the ancestors of modern human populations outside of Africa and their hominin sister groups, notably the Neanderthals, exchanged genetic material in the past. The distribution of these introgressed sequence-tracts along modern-day human genomes provides insight into the ancient structure and migration patterns of these archaic populations. Furthermore, it facilitates studying the selective processes that lead to the accumulation or depletion of introgressed genetic variation. Recent studies have developed methods to localize these introgressed regions, reporting long regions that are depleted of Neanderthal introgression and enriched in genes, suggesting negative selection against the Neanderthal variants. On the other hand, enriched Neanderthal ancestry in hair- and skin-related genes suggests that some introgressed variants facilitated adaptation to new environments. Here, we present a model-based method called diCal-admix and apply it to detect tracts of Neanderthal introgression in modern humans. We demonstrate its efficiency and accuracy through extensive simulations. We use our method to detect introgressed regions in modern human individuals from the 1000 Genomes Project, using a high coverage genome from a Neanderthal individual from the Altai mountains as reference. Our introgression detection results and findings concerning their functional implications are largely concordant with previous studies, and are consistent with weak selection against Neanderthal ancestry. We find some evidence that selection against Neanderthal ancestry was due to higher genetic load in Neanderthals, resulting from small effective population size, rather than Dobzhansky-Müller incompatibilities. Finally, we investigate the role of the X-chromosome in the divergence between Neanderthals and modern humans.

scholarly journals Archaic mitochondrial DNA inserts in modern day nuclear genomes

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Robert Bücking ◽  
Murray P Cox ◽  
Georgi Hudjashov ◽  
Lauri Saag ◽  
Herawati Sudoyo ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Nuclear Dna ◽  
Modern Human ◽  
Sub Saharan Africa ◽  
Next Generation Sequencing Data ◽  
Human Populations ◽  
Sequencing Data ◽  
Modern Humans ◽  
High Coverage ◽  
Nuclear Genomes

Abstract Background Traces of interbreeding of Neanderthals and Denisovans with modern humans in the form of archaic DNA have been detected in the genomes of present-day human populations outside sub-Saharan Africa. Up to now, only nuclear archaic DNA has been detected in modern humans; we therefore attempted to identify archaic mitochondrial DNA (mtDNA) residing in modern human nuclear genomes as nuclear inserts of mitochondrial DNA (NUMTs). Results We analysed 221 high-coverage genomes from Oceania and Indonesia using an approach which identifies reads that map both to the nuclear and mitochondrial DNA. We then classified reads according to the source of the mtDNA, and found one NUMT of Denisovan mtDNA origin, present in 15 analysed genomes; analysis of the flanking region suggests that this insertion is more likely to have happened in a Denisovan individual and introgressed into modern humans with the Denisovan nuclear DNA, rather than in a descendant of a Denisovan female and a modern human male. Conclusions Here we present our pipeline for detecting introgressed NUMTs in next generation sequencing data that can be used on genomes sequenced in the future. Further discovery of such archaic NUMTs in modern humans can be used to detect interbreeding between archaic and modern humans and can reveal new insights into the nature of such interbreeding events.

scholarly journals Archaic mitochondrial DNA inserts in modern day nuclear genomes

2019 ◽  
Author(s):  
Robert Bücking ◽  
Murray P Cox ◽  
Georgi Hudjashov ◽  
Lauri Saag ◽  
Herawati Sudoyo ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Nuclear Dna ◽  
Modern Human ◽  
Next Generation Sequencing Data ◽  
Human Populations ◽  
Sequencing Data ◽  
Modern Humans ◽  
High Coverage ◽  
Nuclear Genomes ◽  
Generation Sequencing

Abstract Background: Traces of interbreeding of Neanderthals and Denisovans with modern humans in the form of archaic DNA have been detected in the genomes of present-day human populations outside sub-Sahara Africa. Up to now, only nuclear archaic DNA has been detected in modern humans; we therefore attempted to identify archaic mitochondrial DNA (mtDNA) residing in modern human nuclear genomes as nuclear inserts of mitochondrial DNA (NUMTs). Results: We analysed 221 high-coverage genomes from Oceania and Indonesia using an approach which identifies reads that map both to the nuclear and mitochondrial DNA. We then classified reads according to the source of the mtDNA, and found one NUMT of Denisovan mtDNA origin; analysis of the flanking region suggests that this insertion is more likely to have happened in a Denisovan individual and introgressed into modern humans with the Denisovan nuclear DNA, rather than in a descendant of a Denisovan female and a modern human male. Conclusions: Here we present our pipeline for detecting introgressed NUMTs in next generation sequencing data that can be used on genomes sequenced in the future. Further discovery of such archaic NUMTs in modern humans can be used to detect interbreeding between archaic and modern humans and can reveal new insights into the nature of such interbreeding events.

scholarly journals Something old, something borrowed: Admixture and adaptation in human evolution

2018 ◽  
Author(s):  
Michael Dannemann ◽  
Fernando Racimo
Keyword(s):  
Human Evolution ◽  
Ancient Dna ◽  
Gene Pool ◽  
Recent Literature ◽  
Genetic Material ◽  
Modern Human ◽  
Human Populations ◽  
Modern Humans ◽  
Functional Assays ◽  
Over Time

Almost a decade ago, the sequencing of ancient DNA from archaic humans - Neanderthals and Denisovans - revealed that modern and archaic humans interbred at least twice during the Pleistocene. The field of human paleogenomics has now turned its attention towards understanding the nature of this genetic legacy in the gene pool of present-day humans. What exactly did modern humans obtain from interbreeding with Neanderthals and Denisovans? Were introgressed genetic material beneficial, neutral or maladaptive? Can differences in phenotypes among present-day human populations be explained by archaic human introgression? These questions are of prime importance for our understanding of recent human evolution, but will require careful computational modeling and extensive functional assays before they can be answered in full. Here, we review the recent literature characterizing introgressed DNA and the likely biological consequences for their modern human carriers. We focus particularly on archaic human haplotypes that were beneficial to modern humans as they expanded across the globe, and on ways to understand how populations harboring these haplotypes evolved over time.

scholarly journals Something old, something borrowed: Admixture and adaptation in human evolution

2018 ◽  
Author(s):  
Michael Dannemann ◽  
Fernando Racimo
Keyword(s):  
Human Evolution ◽  
Ancient Dna ◽  
Gene Pool ◽  
Recent Literature ◽  
Genetic Material ◽  
Modern Human ◽  
Human Populations ◽  
Modern Humans ◽  
Functional Assays ◽  
Over Time

Almost a decade ago, the sequencing of ancient DNA from archaic humans - Neanderthals and Denisovans - revealed that modern and archaic humans interbred at least twice during the Pleistocene. The field of human paleogenomics has now turned its attention towards understanding the nature of this genetic legacy in the gene pool of present-day humans. What exactly did modern humans obtain from interbreeding with Neanderthals and Denisovans? Were introgressed genetic material beneficial, neutral or maladaptive? Can differences in phenotypes among present-day human populations be explained by archaic human introgression? These questions are of prime importance for our understanding of recent human evolution, but will require careful computational modeling and extensive functional assays before they can be answered in full. Here, we review the recent literature characterizing introgressed DNA and the likely biological consequences for their modern human carriers. We focus particularly on archaic human haplotypes that were beneficial to modern humans as they expanded across the globe, and on ways to understand how populations harboring these haplotypes evolved over time.

scholarly journals Archaic mitochondrial DNA inserts in modern day nuclear genomes

2019 ◽  
Author(s):  
Robert Bücking ◽  
Murray P Cox ◽  
Georgi Hudjashov ◽  
Lauri Saag ◽  
Herawati Sudoyo ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Nuclear Dna ◽  
Modern Human ◽  
Next Generation Sequencing Data ◽  
Human Populations ◽  
Sequencing Data ◽  
Modern Humans ◽  
High Coverage ◽  
Nuclear Genomes ◽  
Generation Sequencing

Abstract Background Traces of interbreeding of Neanderthals and Denisovans with modern humans in the form of archaic DNA have been detected in the genomes of present-day human populations outside sub-Sahara Africa. Up to now, only nuclear archaic DNA has been detected in modern humans; we therefore attempted to identify archaic mitochondrial DNA (mtDNA) residing in modern human nuclear genomes as nuclear inserts of mitochondrial DNA (NUMTs). Results We analysed 221 high-coverage genomes from Oceania and Indonesia using an approach which identifies reads that map both to the nuclear and mitochondrial DNA. We then classified reads according to the source of the mtDNA, and found one NUMT of Denisovan mtDNA origin; analysis of the flanking region suggests that this insertion is more likely to have happened in a Denisovan individual and introgressed into modern humans with the Denisovan nuclear DNA, rather than in a descendant of a Denisovan female and a modern human male. Conclusions Here we present our pipeline for detecting introgressed NUMTs in next generation sequencing data that can be used on genomes sequenced in the future. Further discovery of such archaic NUMTs in modern humans can be used to detect interbreeding between archaic and modern humans and can reveal new insights into the nature of such interbreeding events.

scholarly journals Archaic mitochondrial DNA inserts in modern day nuclear genomes

2019 ◽  
Author(s):  
Robert Bücking ◽  
Murray P Cox ◽  
Georgi Hudjashov ◽  
Lauri Saag ◽  
Herawati Sudoyo ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Nuclear Dna ◽  
Modern Human ◽  
Next Generation Sequencing Data ◽  
Human Populations ◽  
Sequencing Data ◽  
Modern Humans ◽  
High Coverage ◽  
Nuclear Genomes ◽  
Generation Sequencing

Abstract Background: Traces of interbreeding of Neanderthals and Denisovans with modern humans in the form of archaic DNA have been detected in the genomes of present-day human populations outside sub-Sahara Africa. Up to now, only nuclear archaic DNA has been detected in modern humans; we therefore attempted to identify archaic mitochondrial DNA (mtDNA) residing in modern human nuclear genomes as nuclear inserts of mitochondrial DNA (NUMTs). Results: We analysed 221 high-coverage genomes from Oceania and Indonesia using an approach which identifies reads that map both to the nuclear and mitochondrial DNA. We then classified reads according to the source of the mtDNA, and found one NUMT of Denisovan mtDNA origin; analysis of the flanking region suggests that this insertion is more likely to have happened in a Denisovan individual and introgressed into modern humans with the Denisovan nuclear DNA, rather than in a descendant of a Denisovan female and a modern human male. Conclusions: Here we present our pipeline for detecting introgressed NUMTs in next generation sequencing data that can be used on genomes sequenced in the future. Further discovery of such archaic NUMTs in modern humans can be used to detect interbreeding between archaic and modern humans and can reveal new insights into the nature of such interbreeding events.

scholarly journals Limits of long-term selection against Neandertal introgression

2019 ◽  
Vol 116 (5) ◽  
pp. 1639-1644 ◽  
Author(s):  
Martin Petr ◽  
Svante Pääbo ◽  
Janet Kelso ◽  
Benjamin Vernot
Keyword(s):  
Negative Selection ◽  
Modern Human ◽  
Model Parameters ◽  
Human Populations ◽  
Modern Humans ◽  
High Coverage ◽  
Protein Coding ◽  
The Past ◽  
Wide Range

Several studies have suggested that introgressed Neandertal DNA was subjected to negative selection in modern humans. A striking observation in support of this is an apparent monotonic decline in Neandertal ancestry observed in modern humans in Europe over the past 45,000 years. Here, we show that this decline is an artifact likely caused by gene flow between modern human populations, which is not taken into account by statistics previously used to estimate Neandertal ancestry. When we apply a statistic that avoids assumptions about modern human demography by taking advantage of two high-coverage Neandertal genomes, we find no evidence for a change in Neandertal ancestry in Europe over the past 45,000 years. We use whole-genome simulations of selection and introgression to investigate a wide range of model parameters and find that negative selection is not expected to cause a significant long-term decline in genome-wide Neandertal ancestry. Nevertheless, these models recapitulate previously observed signals of selection against Neandertal alleles, in particular the depletion of Neandertal ancestry in conserved genomic regions. Surprisingly, we find that this depletion is strongest in regulatory and conserved noncoding regions and in the most conserved portion of protein-coding sequences.

scholarly journals Something old, something borrowed: Admixture and adaptation in human evolution

2018 ◽  
Author(s):  
Michael Dannemann ◽  
Fernando Racimo
Keyword(s):  
Human Evolution ◽  
Ancient Dna ◽  
Gene Pool ◽  
Recent Literature ◽  
Genetic Material ◽  
Modern Human ◽  
Human Populations ◽  
Modern Humans ◽  
Functional Assays ◽  
Over Time

Almost a decade ago, the sequencing of ancient DNA from archaic humans - Neanderthals and Denisovans - revealed that modern and archaic humans interbred at least twice during the Pleistocene. The field of human paleogenomics has now turned its attention towards understanding the nature of this genetic legacy in the gene pool of present-day humans. What exactly did modern humans obtain from interbreeding with Neanderthals and Denisovans? Were introgressed genetic material beneficial, neutral or maladaptive? Can differences in phenotypes among present-day human populations be explained by archaic human introgression? These questions are of prime importance for our understanding of recent human evolution, but will require careful computational modeling and extensive functional assays before they can be answered in full. Here, we review the recent literature characterizing introgressed DNA and the likely biological consequences for their modern human carriers. We focus particularly on archaic human haplotypes that were beneficial to modern humans as they expanded across the globe, and on ways to understand how populations harboring these haplotypes evolved over time.

scholarly journals The evolutionary history of Neandertal and Denisovan Y chromosomes

2020 ◽  
Author(s):  
Martin Petr ◽  
Mateja Hajdinjak ◽  
Qiaomei Fu ◽  
Elena Essel ◽  
Hélène Rougier ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Evolutionary History ◽  
Genetic Load ◽  
Modern Human ◽  
Gene Pools ◽  
Human History ◽  
Effective Population ◽  
Modern Humans ◽  
Y Chromosomes ◽  
History Of

AbstractAncient DNA has allowed the study of various aspects of human history in unprecedented detail. However, because the majority of archaic human specimens preserved well enough for genome sequencing have been female, comprehensive studies of Y chromosomes of Denisovans and Neandertals have not yet been possible. Here we present sequences of the first Denisovan Y chromosomes (Denisova 4 and Denisova 8), as well as the Y chromosomes of three late Neandertals (Spy 94a, Mezmaiskaya 2 and El Sidrón 1253). We find that the Denisovan Y chromosomes split around 700 thousand years ago (kya) from a lineage shared by Neandertal and modern human Y chromosomes, which diverged from each other around 370 kya. The phylogenetic relationships of archaic and modern human Y chromosomes therefore differ from population relationships inferred from their autosomal genomes, and mirror the relationships observed on the level of mitochondrial DNA. This provides strong evidence that gene flow from an early lineage related to modern humans resulted in the replacement of both the mitochondrial and Y chromosomal gene pools in late Neandertals. Although unlikely under neutrality, we show that this replacement is plausible if the low effective population size of Neandertals resulted in an increased genetic load in their Y chromosomes and mitochondrial DNA relative to modern humans.

scholarly journals The Negative Impact of the Hominin’s DPP4 Gene Inherited from Neanderthals to Pandemic of COVID-19

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Sorush Niknamian
Keyword(s):  
Native Americans ◽  
Negative Impact ◽  
Middle Eastern ◽  
Genetic Material ◽  
Modern Human ◽  
Modern Humans ◽  
East Asians ◽  
Dipeptidyl Peptidase 4 ◽  
The Difference ◽  
South Americans

Background: According to preliminary sequences from 2010, 99.7% of the nucleotide sequences of the modern human and Neanderthal genomes are identical, compared to humans sharing around 98.8% of sequences with the chimpanzee. In contrast, the difference between chimpanzees and modern humans is approximately 1,462 mtDNA base pairs. Materials and Methods: Neanderthal-inherited genetic material is found in all non-African populations and was initially reported to comprise 1 to 4 percent of the genome. This fraction was later refined to 1.5 to 2.1 percent. We had gone through many researches of Neanderthals affected gene flow in humans. Results: It is estimated that 20 percent of Neanderthal DNA currently survives in modern humans. Modern human genes involved in making keratin, a protein constituent of skin, hair, and nails, have especially high levels of introgression. For example, approximately 66% of East Asians contain a POUF23L variant introgressed from Neanderthals, while 70% of Europeans possess an introgressed allele of BNC2. Our finding shines a light on an enzyme called dipeptidyl peptidase-4 (DPP4). Scientists already know the protein allows another coronavirus, which causes Middle Eastern respiratory syndrome (MERS), to bind to and enter human cells. The new analysis, of DPP4 gene variants among COVID-19 patients, suggests the enzyme also provides SARS-CoV-2 with a second door into our cells, along with its usual infection route via the angiotensinconverting enzyme 2 (ACE2) receptor on cell surfaces. Conclusion: Most Europeans, Asians, and Native Americans harbor a handful of genes from Neanderthals, up 1.8% to 2.6% of their DNA. Studies of ancient DNA in Neanderthal fossils have shown the hominin’s DPP4 gene subtly differs from the typical human one. Conclusion: The hominin’s DPP4 gene inherited from Neanderthals plays a major role in Immune System Disorders and Lower Immune response in many diseases. This gene plays a major role in affecting humans with COVID-19 and spreading it through the world. All humans contain this gene from 1 to 4 percent. East Asians, Europeans, Middle and South Americans conveys more, hence; native Africans contain less amounts of hominin’s DPP4 gene. Therefore; East Asians, Europeans, Middle and South Americans are prone to severe COVID-19.

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