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ancestral origins and genetic history of tibetan highlanders.the origin of tibetans remains one of the most contentious puzzles in history, anthropology, and genetics. analyses of deeply sequenced (30×-60×) genomes of 38 tibetan highlanders and 39 han chinese lowlanders, together with available data on archaic and modern humans, allow us to comprehensively characterize the ancestral makeup of tibetans and uncover their origins. non-modern human sequences compose ∼6% of the tibetan gene pool and form unique haplotypes in some genomic regions, where denisov ...201627569548
divergent ah receptor ligand selectivity during hominin evolution.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 d ...201627486223
opsin gene repertoires in northern archaic hominids.the neanderthals' northern distribution, hunting techniques, and orbit breadths suggest that they were more active in dim light than modern humans. we surveyed visual opsin genes from four neanderthals and two other archaic hominids to see if they provided additional support for this hypothesis. this analysis was motivated by the observation that alleles responsible for anomalous trichromacy in humans are more common in northern latitudes, by data suggesting that these variants might enhance vis ...201627463216
the origin and evolution of homo sapiens.if we restrict the use of homo sapiens in the fossil record to specimens which share a significant number of derived features in the skeleton with extant h. sapiens, the origin of our species would be placed in the african late middle pleistocene, based on fossils such as omo kibish 1, herto 1 and 2, and the levantine material from skhul and qafzeh. however, genetic data suggest that we and our sister species homo neanderthalensis shared a last common ancestor in the middle pleistocene approxima ...201627298468
ancient dna and human history.we review studies of genomic data obtained by sequencing hominin fossils with particular emphasis on the unique information that ancient dna (adna) can provide about the demographic history of humans and our closest relatives. we concentrate on nuclear genomic sequences that have been published in the past few years. in many cases, particularly in the arctic, the americas, and europe, adna has revealed historical demographic patterns in a way that could not be resolved by analyzing present-day g ...201627274045
neandertals revised.the last decade has seen a significant growth of our knowledge of the neandertals, a population of pleistocene hunter-gatherers who lived in (western) eurasia between ∼400,000 and 40,000 y ago. starting from a source population deep in the middle pleistocene, the hundreds of thousands of years of relative separation between african and eurasian groups led to the emergence of different phenotypes in late pleistocene europe and africa. both recently obtained genetic evidence and archeological data ...201627274044
neanderthal genomics suggests a pleistocene time frame for the first epidemiologic transition.high quality altai neanderthal and denisovan genomes are revealing which regions of archaic hominin dna have persisted in the modern human genome. a number of these regions are associated with response to infection and immunity, with a suggestion that derived neanderthal alleles found in modern europeans and east asians may be associated with autoimmunity. as such neanderthal genomes are an independent line of evidence of which infectious diseases neanderthals were genetically adapted to. sympat ...201627063929
why are there no persisting hybrids of humans with denisovans, neanderthals, or anyone else? 201627044111
the combined landscape of denisovan and neanderthal ancestry in present-day humans.some present-day humans derive up to ∼5% [1] of their ancestry from archaic denisovans, an even larger proportion than the ∼2% from neanderthals [2]. we developed methods that can disambiguate the locations of segments of denisovan and neanderthal ancestry in present-day humans and applied them to 257 high-coverage genomes from 120 diverse populations, among which were 20 individual oceanians with high denisovan ancestry [3]. in oceanians, the average size of denisovan fragments is larger than n ...201627032491
the out of africa hypothesis and the ancestry of recent humans: cherchez la femme (et l'homme).the out of africa hypothesis (ooah) has been a mainstay in the discussion of human evolution since its presentation in the 1980's. however, recent advances in palaeontology and molecular genetics have made it possible to examine the hypothesis in a manner that was inconceivable at the time of its proposal. the palaeontological progress relates to early homo finds in the caucasus, denisova finds in the altai mountains and neanderthal finds in a wide range of localities from the altai mountains, t ...201626995655
excavating neandertal and denisovan dna from the genomes of melanesian individuals.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 3 ...201626989198
nuclear dna sequences from the middle pleistocene sima de los huesos hominins.a unique assemblage of 28 hominin individuals, found in sima de los huesos in the sierra de atapuerca in spain, has recently been dated to approximately 430,000 years ago. an interesting question is how these middle pleistocene hominins were related to those who lived in the late pleistocene epoch, in particular to neanderthals in western eurasia and to denisovans, a sister group of neanderthals so far known only from southern siberia. while the sima de los huesos hominins share some derived mor ...201626976447
the uromodulin gene locus shows evidence of pathogen adaptation through human evolution.common variants in the umod gene encoding uromodulin, associated with risk of hypertension and ckd in the general population, increase umod expression and urinary excretion of uromodulin, causing salt-sensitive hypertension and renal lesions. to determine the effect of selective pressure on variant frequency, we investigated the allelic frequency of the lead umod variant rs4293393 in 156 human populations, in eight ancient human genomes, and in primate genomes. the t allele of rs4293393, associa ...201626966016
erratum for the report "ancient ethiopian genome reveals extensive eurasian admixture in eastern africa" (previously titled "ancient ethiopian genome reveals extensive eurasian admixture throughout the african continent") by m. gallego llorente, e. r. jones, a. eriksson, v. siska, k. w. arthur, j. w. arthur, m. c. curtis, j. t. stock, m. coltorti, p. pieruccini, s. stretton, f. brock, t. higham, y. park, m. hofreiter, d. g. bradley, j. bhak, r. pinhasi, a. manica.in the report “ancient ethiopian genome reveals extensive eurasian admixture in eastern africa,” the results were affected by a bioinformatics error. a script necessary to convert the input produced by samtools v0.1.19 to be compatible with plink was not run when merging the ancient genome, mota, with the contemporary populations snp panel, leading to homozygote positions to the human reference genome being dropped as missing data (the analysis of admixture with neandertals and denisovans was no ...201626912899
the evolutionary history of genes involved in spoken and written language: beyond foxp2.humans possess a communication system based on spoken and written language. other animals can learn vocalization by imitation, but this is not equivalent to human language. many genes were described to be implicated in language impairment (li) and developmental dyslexia (dd), but their evolutionary history has not been thoroughly analyzed. herein we analyzed the evolution of ten genes involved in dd and li. results show that the evolutionary history of li genes for mammals and aves was comparabl ...201626912479
epigenetics: it's getting old. past meets future in paleoepigenetics.recent years have witnessed the rise of ancient dna (adna) technology, allowing comparative genomics to be carried out at unprecedented time resolution. while it is relatively straightforward to use adna to identify recent genomic changes, it is much less clear how to utilize it to study changes in epigenetic regulation. here we review recent works demonstrating that highly degraded adna still contains sufficient information to allow reconstruction of epigenetic signals, including dna methylatio ...201626898827
model-based analyses of whole-genome data reveal a complex evolutionary history involving archaic introgression in central african pygmies.comparisons of whole-genome sequences from ancient and contemporary samples have pointed to several instances of archaic admixture through interbreeding between the ancestors of modern non-africans and now extinct hominids such as neanderthals and denisovans. one implication of these findings is that some adaptive features in contemporary humans may have entered the population via gene flow with archaic forms in eurasia. within africa, fossil evidence suggests that anatomically modern humans (am ...201626888264
ancient gene flow from early modern humans into eastern neanderthals.it has been shown that neanderthals contributed genetically to modern humans outside africa 47,000-65,000 years ago. here we analyse the genomes of a neanderthal and a denisovan from the altai mountains in siberia together with the sequences of chromosome 21 of two neanderthals from spain and croatia. we find that a population that diverged early from other modern humans in africa contributed genetically to the ancestors of neanderthals from the altai mountains roughly 100,000 years ago. by cont ...201626886800
tlrs of our fathers.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.201626885854
analysis of ancient dna in microbial ecology.the development of next-generation sequencing has led to a breakthrough in the analysis of ancient genomes, and the subsequent genomic analyses of the skeletal remains of ancient humans have revolutionized the knowledge of the evolution of our species, including the discovery of a new hominin, and demonstrated admixtures with more distantly related archaic populations such as neandertals and denisovans. moreover, it has also yielded novel insights into the evolution of ancient pathogens. the ana ...201626791510
introgression of neandertal- and denisovan-like haplotypes contributes to adaptive variation in human toll-like receptors.pathogens and the diseases they cause have been among the most important selective forces experienced by humans during their evolutionary history. although adaptive alleles generally arise by mutation, introgression can also be a valuable source of beneficial alleles. archaic humans, who lived in europe and western asia for more than 200,000 years, were probably well adapted to this environment and its local pathogens. it is therefore conceivable that modern humans entering europe and western as ...201626748514
molecular evolution of wdr62, a gene that regulates neocorticogenesis.human brain evolution is characterized by dramatic expansion in cerebral cortex size. wdr62 (wd repeat domain 62) is one of the important gene in controlling human cortical development. mutations in wdr62 lead to primary microcephaly, a neurodevelopmental disease characterized by three to four fold reduction in cerebral cortex size of affected individuals. this study analyzes comparative protein evolutionary rate to provide a useful insight into the molecular evolution of wdr62 and hence pinpoin ...201627114917
one pedigree we all may have come from - did adam and eve have the chromosome 2 fusion?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.201627708712
denisovans, melanesians, europeans, and neandertals: the confusion of dna assumptions and the biological species concept.a number of recent articles have appeared on the denisova fossil remains and attempts to produce dna sequences from them. one of these recently appeared in science by vernot et al. (science 352:235-239, 2016). we would like to advance an alternative interpretation of the data presented. one concerns the problem of contamination/degradation of the determined dna sequenced. just as the publication of the first neandertal sequence included an interpretation that argued that neandertals had not cont ...201627517578
hominin interbreeding and the evolution of human variation.mitochondrial eve confirms the "out of africa" theory, but the evidence also supports interbreeding between homo sapiens and other hominins: neanderthals, denisovans, and homo heidelbergensis. this article explains how interbreeding between early h. sapiens and archaic hominins occurred. the availability of edible insects in east asia aided the spread of the unaggressive, highly cooperative neanderthals, who interbred with h. sapiens in asia, resulting in a higher admixture of neanderthal dna in ...201627429943
paleogenetics and past infections: the two faces of the coin of human immune evolution.with the advent of next-generation sequencing, paleogenetics has considerably expanded over the past few years and notably encompassed the characterization of the genomes of archaic humans who lived more than 30,000 years ago. these paleogenetics investigations have revealed that admixture between modern and archaic humans occurred, with neanderthals having contributed to 1.5% to 2.1% of modern eurasian genomes, and denisovans to 3% to 6% of modern melanesian genomes and to approximately 0.2% of ...201627337483
genetic evidence of human adaptation to a cooked diet.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 ...201626979798
transmission between archaic and modern human ancestors during the evolution of the oncogenic human papillomavirus 16.every human suffers through life a number of papillomaviruses (pvs) infections, most of them asymptomatic. a notable exception are persistent infections by human papillomavirus 16 (hpv16), the most oncogenic infectious agent for humans and responsible for most infection-driven anogenital cancers. oncogenic potential is not homogeneous among hpv16 lineages, and genetic variation within hpv16 exhibits some geographic structure. however, an in-depth analysis of the hpv16 evolutionary history was st ...201728025273
neanderthals and denisovans as biological invaders. 201728860198
the mobile element locator tool (melt): population-scale mobile element discovery and biology.mobile element insertions (meis) represent ~25% of all structural variants in human genomes. moreover, when they disrupt genes, meis can influence human traits and diseases. therefore, meis should be fully discovered along with other forms of genetic variation in whole genome sequencing (wgs) projects involving population genetics, human diseases, and clinical genomics. here, we describe the mobile element locator tool (melt), which was developed as part of the 1000 genomes project to perform me ...201728855259
the mitonuclear dimension of neanderthal and denisovan ancestry in modern human genomes.some human populations interbred with neanderthals and denisovans, resulting in substantial contributions to modern-human genomes. therefore, it is now possible to use genomic data to investigate mechanisms that shaped historical gene flow between humans and our closest hominin relatives. more generally, in eukaryotes, mitonuclear interactions have been argued to play a disproportionate role in generating reproductive isolation. there is no evidence of mtdna introgression into modern human popul ...201728854627
detecting ancient positive selection in humans using extended lineage sorting.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 ...201728784836
early history of neanderthals and denisovans.extensive dna sequence data have made it possible to reconstruct human evolutionary history in unprecedented detail. we introduce a method to study the past several hundred thousand years. our results show that (i) the neanderthal-denisovan lineage declined to a small size just after separating from the modern lineage, (ii) neanderthals and denisovans separated soon thereafter, and (iii) the subsequent neanderthal population was large and deeply subdivided. they also (iv) support previous estima ...201728784789
the osteoarthritis and height gdf5 locus yields its secrets.a new study reports molecular characterization of the gdf5 locus, which is associated with osteoarthritis risk and adult height in humans. this study provides evidence of positive selection for short stature at gdf5 in modern humans, as well as in archaic neandertals and denisovans.201728747750
human occupation of northern australia by 65,000 years ago.the time of arrival of people in australia is an unresolved question. it is relevant to debates about when modern humans first dispersed out of africa and when their descendants incorporated genetic material from neanderthals, denisovans and possibly other hominins. humans have also been implicated in the extinction of australia's megafauna. here we report the results of new excavations conducted at madjedbebe, a rock shelter in northern australia. artefacts in primary depositional context are c ...201728726833
detecting ancient positive selection in humans using extended lineage sorting.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 ...201728720580
a fourth denisovan individual.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 (denisova 2), discovere ...201728695206
deeply divergent archaic mitochondrial genome provides lower time boundary for african gene flow into neanderthals.ancient dna is revealing new insights into the genetic relationship between pleistocene hominins and modern humans. nuclear dna indicated neanderthals as a sister group of denisovans after diverging from modern humans. however, the closer affinity of the neanderthal mitochondrial dna (mtdna) to modern humans than denisovans has recently been suggested as the result of gene flow from an african source into neanderthals before 100,000 years ago. here we report the complete mtdna of an archaic femu ...201728675384
ancient selection for derived alleles at a gdf5 enhancer influencing human growth and osteoarthritis risk.variants in gdf5 are associated with human arthritis and decreased height, but the causal mutations are still unknown. we surveyed the gdf5 locus for regulatory regions in transgenic mice and fine-mapped separate enhancers controlling expression in joints versus growing ends of long bones. a large downstream regulatory region contains a novel growth enhancer (grow1), which is required for normal gdf5 expression at ends of developing bones and for normal bone lengths in vivo. human grow1 contains ...201728671685
a tale of agriculturalists and hunter-gatherers: exploring the thrifty genotype hypothesis in native south americans.to determine genetic differences between agriculturalist and hunter-gatherer southern native american populations for selected metabolism-related markers and to test whether neel's thrifty genotype hypothesis (tgh) could explain the genetic patterns observed in these populations.201728464262
neandertal and denisovan dna from pleistocene sediments.although a rich record of pleistocene human-associated archaeological assemblages exists, the scarcity of hominin fossils often impedes the understanding of which hominins occupied a site. using targeted enrichment of mitochondrial dna, we show that cave sediments represent a rich source of ancient mammalian dna that often includes traces of hominin dna, even at sites and in layers where no hominin remains have been discovered. by automation-assisted screening of numerous sediment samples, we de ...201728450384
meiotic genes are enriched in regions of reduced archaic ancestry.about 1-6% of the genetic ancestry of modern humans today originates from admixture with archaic humans. it has recently been shown that autosomal genomic regions with a reduced proportion of neanderthal and denisovan ancestries are significantly enriched in genes that are more expressed in testis than in other tissues. to determine whether a cellular segregation pattern would exist, we combined maps of archaic introgression with a cross-analysis of three transcriptomic datasets deciphering the ...201728444387
an updated age for the xujiayao hominin from the nihewan basin, north china: implications for middle pleistocene human evolution in east asia.the xujiayao site in the nihewan basin (north china) is one of the most important paleolithic sites in east asia. twenty homo fossils, which were previously assigned to an archaic homo sapiens group, have been excavated along with more than 30,000 lithic artifacts and ∼5000 mammalian fossil specimens. dating of the xujiayao hominin has been pursued since its excavation in the 1970s, but its age has remained controversial because of limitations of the dating techniques that have been applied to a ...201728434540
elucidating the origin of hla-b*73 allelic lineage: did modern humans benefit by archaic introgression?a previous study reported that some of the human leukocyte antigen (hla) alleles and haplotypes in present-day humans were acquired by admixture with archaic humans; specifically, an exceptionally diverged hla-b*73 allele was proposed to be transmitted from denisovans, although the dna sequence of hla-b*73 has not been detected in the denisovan genome. here, we argue against the hypothesis that hla-b*73 introgressed from denisovans into early modern humans. a phylogenetic analysis revealed that ...201727695917
or2m3: a highly specific and narrowly tuned human odorant receptor for the sensitive detection of onion key food odorant 3-mercapto-2-methylpentan-1-ol.the detection of key food odorants appears to be an important capability of odorant receptors. here, thiols occupy an outstanding position among the 230 known key food odorants because of their very low odor thresholds. members of the homologous series of 3-mercapto-2-methylalkan-1-ols have been described as onion key food odorants or food constituents and are detected at logarithmically different thresholds. 3-mercapto-2-methylpentan-1-ol being the only key food odorant within this series also ...201727916748
fire usage and ancient hominin detoxification genes: protective ancestral variants dominate while additional derived risk variants appear in modern humans.studies of the defence capacity of ancient hominins against toxic substances may contribute importantly to the reconstruction of their niche, including their diets and use of fire. fire usage implies frequent exposure to hazardous compounds from smoke and heated food, known to affect general health and fertility, probably resulting in genetic selection for improved detoxification. to investigate whether such genetic selection occurred, we investigated the alleles in neanderthals, denisovans and ...201727655273
discerning the origins of the negritos, first sundaland people: deep divergence and archaic admixture.human presence in southeast asia dates back to at least 40,000 years ago, when the current islands formed a continental shelf called sundaland. in the philippine islands, peninsular malaysia, and andaman islands, there exist indigenous groups collectively called negritos whose ancestry can be traced to the "first sundaland people." to understand the relationship between these negrito groups and their demographic histories, we generated genome-wide single nucleotide polymorphism data in the phili ...201728854687
evolutionary history of tibetans inferred from whole-genome sequencing.the indigenous people of the tibetan plateau have been the subject of much recent interest because of their unique genetic adaptations to high altitude. recent studies have demonstrated that the tibetan epas1 haplotype is involved in high altitude-adaptation and originated in an archaic denisovan-related population. we sequenced the whole-genomes of 27 tibetans and conducted analyses to infer a detailed history of demography and natural selection of this population. we detected evidence of popul ...201728448578
cognitive functions: human vs. animal - 4:1 advantage |-fam72-srgap2-|.with the advent of computational genomics, an intensive search is underway for unique biomarkers for homo sapiens that could be used to differentiate taxa within the hominoidea, in particular to distinguish homo from the apes (pan, gorilla, pongo, and hylobates) and species or subspecies within the genus homo (h. sapiens, h. heidelbergensis, h. neanderthalensis, h. erectus, and the denisovans). here, we suggest that the |-fam72-srgap2-| (family with sequence similarity 72/slit-robo rho gtpase ac ...201728255958
gain-of-function egln1 prolyl hydroxylase (phd2 d4e:c127s) in combination with epas1 (hif-2α) polymorphism lowers hemoglobin concentration in tibetan highlanders.tibetans have lived at high altitude for generations and are thought to be genetically adapted to hypoxic environments. most are protected from hypoxia-induced polycythemia, and a haplotype of epas1, encoding hypoxia-inducible factor (hif-2α), has been associated with lower hemoglobin levels. we earlier reported a tibetan-specific egln1 haplotype encoding phd2 which abrogates hif augmentation in hypoxia. we genotyped 347 tibetan individuals from varying altitudes for both the tibetan-specific eg ...201728233034
evolutionary selected tibetan variants of hif pathway and risk of lung cancer.tibetans existed in high altitude for ~25 thousand years and have evolutionary selected unique haplotypes assumed to be beneficial to hypoxic adaptation. egln1/phd2 and epas1/hif-2α, both crucial components of hypoxia sensing, are the two best-established loci contributing to high altitude adaptation. the co-adapted tibetan-specific haplotype encoding for phd2:p.[d4e/c127s] promotes increased hif degradation under hypoxic conditions. the tibetan-specific 200 kb epas1 haplotype introgressed from ...201728036300
archaic adaptive introgression in tbx15/wars2.a recent study conducted the first genome-wide scan for selection in inuit from greenland using single nucleotide polymorphism chip data. here, we report that selection in the region with the second most extreme signal of positive selection in greenlandic inuit favored a deeply divergent haplotype that is closely related to the sequence in the denisovan genome, and was likely introgressed from an archaic population. the region contains two genes, wars2 and tbx15, and has previously been associat ...201728007980
chromosome-specific centromere sequences provide an estimate of the ancestral chromosome 2 fusion event in hominin genomes.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 ancestr ...201727423248
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