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https://www.readbyqxmd.com/read/29285967/the-genomic-health-of-ancient-hominins
#1
Ali J Berens, Taylor L Cooper, Joseph Lachance
The genomes of ancient humans, Neandertals, and Denisovans contain many alleles that influence disease risks. Using genotypes at 3,180 disease-associated loci, we estimated the disease burden of 147 ancient genomes. After correcting for missing data, genetic risk scores (GRS) were generated for nine disease categories and the set of all combined diseases. We used these genetic risk scores to examine the effects of different types of subsistence, geography, and sample age on the number of risk alleles in each ancient genome...
January 2017: Human Biology
https://www.readbyqxmd.com/read/28983028/neandertal-genome-reveals-greater-legacy-in-the-living
#2
Ann Gibbons
No abstract text is available yet for this article.
October 6, 2017: Science
https://www.readbyqxmd.com/read/28982794/a-high-coverage-neandertal-genome-from-vindija-cave-in-croatia
#3
Kay Prüfer, Cesare de Filippo, Steffi Grote, Fabrizio Mafessoni, Petra Korlević, Mateja Hajdinjak, Benjamin Vernot, Laurits Skov, Pinghsun Hsieh, Stéphane Peyrégne, David Reher, Charlotte Hopfe, Sarah Nagel, Tomislav Maricic, Qiaomei Fu, Christoph Theunert, Rebekah Rogers, Pontus Skoglund, Manjusha Chintalapati, Michael Dannemann, Bradley J Nelson, Felix M Key, Pavao Rudan, Željko Kućan, Ivan Gušić, Liubov V Golovanova, Vladimir B Doronichev, Nick Patterson, David Reich, Evan E Eichler, Montgomery Slatkin, Mikkel H Schierup, Aida M Andrés, Janet Kelso, Matthias Meyer, Svante Pääbo
To date, the only Neandertal genome that has been sequenced to high quality is from an individual found in Southern Siberia. We sequenced the genome of a female Neandertal from ~50,000 years ago from Vindija Cave, Croatia, to ~30-fold genomic coverage. She carried 1.6 differences per 10,000 base pairs between the two copies of her genome, fewer than present-day humans, suggesting that Neandertal populations were of small size. Our analyses indicate that she was more closely related to the Neandertals that mixed with the ancestors of present-day humans living outside of sub-Saharan Africa than the previously sequenced Neandertal from Siberia, allowing 10 to 20% more Neandertal DNA to be identified in present-day humans, including variants involved in low-density lipoprotein cholesterol concentrations, schizophrenia, and other diseases...
November 3, 2017: Science
https://www.readbyqxmd.com/read/28890534/harnessing-ancient-genomes-to-study-the-history-of-human-adaptation
#4
REVIEW
Stephanie Marciniak, George H Perry
The past several years have witnessed an explosion of successful ancient human genome-sequencing projects, with genomic-scale ancient DNA data sets now available for more than 1,100 ancient human and archaic hominin (for example, Neandertal) individuals. Recent 'evolution in action' analyses have started using these data sets to identify and track the spatiotemporal trajectories of genetic variants associated with human adaptations to novel and changing environments, agricultural lifestyles, and introduced or co-evolving pathogens...
November 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/28720580/detecting-ancient-positive-selection-in-humans-using-extended-lineage-sorting
#5
Stéphane Peyrégne, Michael James Boyle, Michael Dannemann, Kay Prüfer
Natural selection that affected modern humans early in their evolution has likely shaped some of the traits that set present-day humans apart from their closest extinct and living relatives. The ability to detect ancient natural selection in the human genome could provide insights into the molecular basis for these human-specific traits. Here, we introduce a method for detecting ancient selective sweeps by scanning for extended genomic regions where our closest extinct relatives, Neandertals and Denisovans, fall outside of the present-day human variation...
September 2017: Genome Research
https://www.readbyqxmd.com/read/28622932/an-evolutionary-medicine-perspective-on-neandertal-extinction
#6
Alexis P Sullivan, Marc de Manuel, Tomas Marques-Bonet, George H Perry
The Eurasian sympatry of Neandertals and anatomically modern humans - beginning at least 45,000 years ago and possibly lasting for more than 5000 years - has sparked immense anthropological interest into the factors that potentially contributed to Neandertal extinction. Among many different hypotheses, the "differential pathogen resistance" extinction model posits that Neandertals were disproportionately affected by exposure to novel infectious diseases that were transmitted during the period of spatiotemporal sympatry with modern humans...
July 2017: Journal of Human Evolution
https://www.readbyqxmd.com/read/28366169/functional-implications-of-neandertal-introgression-in-modern-humans
#7
Michael Dannemann, Kay Prüfer, Janet Kelso
BACKGROUND: Admixture between early modern humans and Neandertals approximately 50,000-60,000 years ago has resulted in 1.5-4% Neandertal ancestry in the genomes of present-day non-Africans. Evidence is accumulating that some of these archaic alleles are advantageous for modern humans, while others are deleterious; however, the major mechanism by which these archaic alleles act has not been fully explored. RESULTS: Here we assess the contributions of introgressed non-synonymous and regulatory variants to modern human protein and gene expression variation...
April 3, 2017: Genome Biology
https://www.readbyqxmd.com/read/28044971/-innate-immunity-and-human-diseases-from-archaic-introgression-to-natural-selection
#8
REVIEW
Matthieu Deschamps, Lluís Quintana-Murci
Throughout evolution, humans have had to face strong variation in environmental conditions, with pathogens being among the strongest threats that our species has encountered. The use of population genetic approaches provides novel insights into how natural selection imposed by pathogen pressures, in its different forms and intensities, has shaped the patterns of diversity of the human genome at the population level. These studies help to distinguish genes playing essential, non-redundant functions in host defence from genes variation in which has conferred selective advantages to specific human populations and/or has been acquired through admixture with archaic hominins, such as Neandertals...
December 2016: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/27768888/genetic-adaptation-and-neandertal-admixture-shaped-the-immune-system-of-human-populations
#9
Hélène Quach, Maxime Rotival, Julien Pothlichet, Yong-Hwee Eddie Loh, Michael Dannemann, Nora Zidane, Guillaume Laval, Etienne Patin, Christine Harmant, Marie Lopez, Matthieu Deschamps, Nadia Naffakh, Darragh Duffy, Anja Coen, Geert Leroux-Roels, Frederic Clément, Anne Boland, Jean-François Deleuze, Janet Kelso, Matthew L Albert, Lluis Quintana-Murci
Humans differ in the outcome that follows exposure to life-threatening pathogens, yet the extent of population differences in immune responses and their genetic and evolutionary determinants remain undefined. Here, we characterized, using RNA sequencing, the transcriptional response of primary monocytes from Africans and Europeans to bacterial and viral stimuli-ligands activating Toll-like receptor pathways (TLR1/2, TLR4, and TLR7/8) and influenza virus-and mapped expression quantitative trait loci (eQTLs)...
October 20, 2016: Cell
https://www.readbyqxmd.com/read/27708712/one-pedigree-we-all-may-have-come-from-did-adam-and-eve-have-the-chromosome-2-fusion
#10
Paweł Stankiewicz
BACKGROUND: In contrast to Great Apes, who have 48 chromosomes, modern humans and likely Neandertals and Denisovans have and had, respectively, 46 chromosomes. The reduction in chromosome number was caused by the head-to-head fusion of two ancestral chromosomes to form human chromosome 2 (HSA2) and may have contributed to the reproductive barrier with Great Apes. RESULTS: Next generation sequencing and molecular clock analyses estimated that this fusion arose prior to our last common ancestor with Neandertal and Denisovan hominins ~ 0...
2016: Molecular Cytogenetics
https://www.readbyqxmd.com/read/27486223/divergent-ah-receptor-ligand-selectivity-during-hominin-evolution
#11
Troy D Hubbard, Iain A Murray, William H Bisson, Alexis P Sullivan, Aswathy Sebastian, George H Perry, Nina G Jablonski, Gary H Perdew
We have identified a fixed nonsynonymous sequence difference between humans (Val381; derived variant) and Neandertals (Ala381; ancestral variant) in the ligand-binding domain of the aryl hydrocarbon receptor (AHR) gene. In an exome sequence analysis of four Neandertal and Denisovan individuals compared with nine modern humans, there are only 90 total nucleotide sites genome-wide for which archaic hominins are fixed for the ancestral nonsynonymous variant and the modern humans are fixed for the derived variant...
October 2016: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/27423248/chromosome-specific-centromere-sequences-provide-an-estimate-of-the-ancestral-chromosome-2-fusion-event-in-hominin-genomes
#12
Karen H Miga
Human chromosome 2 is a product of a telomere fusion of two ancestral chromosomes and loss/degeneration of one of the two original centromeres. Genomic signatures of this event are limited to inverted telomeric repeats at the precise site of chromosomal fusion and to the small amount of relic centromeric sequences that remain on 2q21.2. Unlike the site of fusion, which is enriched for sequences that are shared elsewhere in the human genome, the region of the nonfunctioning and degenerate ancestral centromere appears to share limited similarity with other sites in the human genome, thereby providing an opportunity to study this genomic arrangement in short, fragmented ancient DNA genomic datasets...
January 2017: Journal of Heredity
https://www.readbyqxmd.com/read/27058445/the-divergence-of-neandertal-and-modern-human-y-chromosomes
#13
Fernando L Mendez, G David Poznik, Sergi Castellano, Carlos D Bustamante
Sequencing the genomes of extinct hominids has reshaped our understanding of modern human origins. Here, we analyze ∼120 kb of exome-captured Y-chromosome DNA from a Neandertal individual from El Sidrón, Spain. We investigate its divergence from orthologous chimpanzee and modern human sequences and find strong support for a model that places the Neandertal lineage as an outgroup to modern human Y chromosomes-including A00, the highly divergent basal haplogroup. We estimate that the time to the most recent common ancestor (TMRCA) of Neandertal and modern human Y chromosomes is ∼588 thousand years ago (kya) (95% confidence interval [CI]: 447-806 kya)...
April 7, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/26989198/excavating-neandertal-and-denisovan-dna-from-the-genomes-of-melanesian-individuals
#14
Benjamin Vernot, Serena Tucci, Janet Kelso, Joshua G Schraiber, Aaron B Wolf, Rachel M Gittelman, Michael Dannemann, Steffi Grote, Rajiv C McCoy, Heather Norton, Laura B Scheinfeldt, David A Merriwether, George Koki, Jonathan S Friedlaender, Jon Wakefield, Svante Pääbo, Joshua M Akey
Although Neandertal sequences that persist in the genomes of modern humans have been identified in Eurasians, comparable studies in people whose ancestors hybridized with both Neandertals and Denisovans are lacking. We developed an approach to identify DNA inherited from multiple archaic hominin ancestors and applied it to whole-genome sequences from 1523 geographically diverse individuals, including 35 previously unknown Island Melanesian genomes. In aggregate, we recovered 1.34 gigabases and 303 megabases of the Neandertal and Denisovan genome, respectively...
April 8, 2016: Science
https://www.readbyqxmd.com/read/26979798/genetic-evidence-of-human-adaptation-to-a-cooked-diet
#15
Rachel N Carmody, Michael Dannemann, Adrian W Briggs, Birgit Nickel, Emily E Groopman, Richard W Wrangham, Janet Kelso
Humans have been argued to be biologically adapted to a cooked diet, but this hypothesis has not been tested at the molecular level. Here, we combine controlled feeding experiments in mice with comparative primate genomics to show that consumption of a cooked diet influences gene expression and that affected genes bear signals of positive selection in the human lineage. Liver gene expression profiles in mice fed standardized diets of meat or tuber were affected by food type and cooking, but not by caloric intake or consumer energy balance...
April 13, 2016: Genome Biology and Evolution
https://www.readbyqxmd.com/read/26937625/ancient-hybridization-and-genomic-stabilization-in-a-swordtail-fish
#16
Molly Schumer, Rongfeng Cui, Daniel L Powell, Gil G Rosenthal, Peter Andolfatto
A rapidly increasing body of work is revealing that the genomes of distinct species often exhibit hybrid ancestry, presumably due to postspeciation hybridization between closely related species. Despite the growing number of documented cases, we still know relatively little about how genomes evolve and stabilize following hybridization, and to what extent hybridization is functionally relevant. Here, we examine the case of Xiphophorus nezahualcoyotl, a teleost fish whose genome exhibits significant hybrid ancestry...
June 2016: Molecular Ecology
https://www.readbyqxmd.com/read/26912863/the-phenotypic-legacy-of-admixture-between-modern-humans-and-neandertals
#17
Corinne N Simonti, Benjamin Vernot, Lisa Bastarache, Erwin Bottinger, David S Carrell, Rex L Chisholm, David R Crosslin, Scott J Hebbring, Gail P Jarvik, Iftikhar J Kullo, Rongling Li, Jyotishman Pathak, Marylyn D Ritchie, Dan M Roden, Shefali S Verma, Gerard Tromp, Jeffrey D Prato, William S Bush, Joshua M Akey, Joshua C Denny, John A Capra
Many modern human genomes retain DNA inherited from interbreeding with archaic hominins, such as Neandertals, yet the influence of this admixture on human traits is largely unknown. We analyzed the contribution of common Neandertal variants to over 1000 electronic health record (EHR)-derived phenotypes in ~28,000 adults of European ancestry. We discovered and replicated associations of Neandertal alleles with neurological, psychiatric, immunological, and dermatological phenotypes. Neandertal alleles together explained a significant fraction of the variation in risk for depression and skin lesions resulting from sun exposure (actinic keratosis), and individual Neandertal alleles were significantly associated with specific human phenotypes, including hypercoagulation and tobacco use...
February 12, 2016: Science
https://www.readbyqxmd.com/read/26885854/tlrs-of-our-fathers
#18
COMMENT
Mihai G Netea, Leo A B Joosten
Two new studies published in The American Journal of Human Genetics (Dannemann et al., 2016; Deschamps et al., 2016) show that introgression of innate immune genes from Neandertals and Denisovans contributed to the modern genome of European and Asian, but not African, populations, and this might partly explain differences in susceptibility to immune-mediated diseases.
February 16, 2016: Immunity
https://www.readbyqxmd.com/read/26852813/virtual-ancestor-reconstruction-revealing-the-ancestor-of-modern-humans-and-neandertals
#19
Aurélien Mounier, Marta Mirazón Lahr
The timing and geographic origin of the common ancestor of modern humans and Neandertals remain controversial. A poor Pleistocene hominin fossil record and the evolutionary complexities introduced by dispersals and regionalisation of lineages have fuelled taxonomic uncertainty, while new ancient genomic data have raised completely new questions. Here, we use maximum likelihood and 3D geometric morphometric methods to predict possible morphologies of the last common ancestor of modern humans and Neandertals from a simplified, fully resolved phylogeny...
February 2016: Journal of Human Evolution
https://www.readbyqxmd.com/read/26849112/a-burden-of-rare-variants-associated-with-extremes-of-gene-expression-in-human-peripheral-blood
#20
Jing Zhao, Idowu Akinsanmi, Dalia Arafat, T J Cradick, Ciaran M Lee, Samridhi Banskota, Urko M Marigorta, Gang Bao, Greg Gibson
In order to evaluate whether rare regulatory variants in the vicinity of promoters are likely to impact gene expression, we conducted a novel burden test for enrichment of rare variants at the extremes of expression. After sequencing 2-kb promoter regions of 472 genes in 410 healthy adults, we performed a quadratic regression of rare variant count on bins of peripheral blood transcript abundance from microarrays, summing over ranks of all genes. After adjusting for common eQTLs and the major axes of gene expression covariance, a highly significant excess of variants with minor allele frequency less than 0...
February 4, 2016: American Journal of Human Genetics
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