Publications

the complete mitochondrial dna genome of an unknown hominin from southern siberia.	with the exception of neanderthals, from which dna sequences of numerous individuals have now been determined, the number and genetic relationships of other hominin lineages are largely unknown. here we report a complete mitochondrial (mt) dna sequence retrieved from a bone excavated in 2008 in denisova cave in the altai mountains in southern siberia. it represents a hitherto unknown type of hominin mtdna that shares a common ancestor with anatomically modern human and neanderthal mtdnas about 1 ...	2010	20336068
the denisova hominin need not be an out of africa story.		2011	21129766
genetic history of an archaic hominin group from denisova cave in siberia.	using dna extracted from a finger bone found in denisova cave in southern siberia, we have sequenced the genome of an archaic hominin to about 1.9-fold coverage. this individual is from a group that shares a common origin with neanderthals. this population was not involved in the putative gene flow from neanderthals into eurasians; however, the data suggest that it contributed 4-6% of its genetic material to the genomes of present-day melanesians. we designate this hominin population 'denisovans ...	2010	21179161
ancient origin of a deletion in human bst2/tetherin that confers protection against viral zoonoses.	bst2/tetherin is an antiviral factor that blocks the release of enveloped virions from infected cells. recent data suggest that efficient bst2 antagonism was a prerequisite for the global spread of hiv/aids. most simian immunodeficiency viruses (sivs), including the direct precursors of hiv, use their nef protein to antagonize bst2 of their respective host species. human bst2, however, contains a five amino acid deletion in its cytoplasmic domain that confers resistance to nef. thus, this antivi ...	2011	21796732
on characterizing adaptive events unique to modern humans.	ever since the first draft of the human genome was completed in 2001 there has been increased interest in identifying genetic changes that are uniquely human, which could account for our distinct morphological and cognitive capabilities with respect to other apes. recently, draft sequences of two extinct hominin genomes, a neanderthal and denisovan, have been released. these two genomes provide a much greater resolution to identify human-specific genetic differences than the chimpanzee, our clos ...	2011	21803765
cross-comparison of the genome sequences from human, chimpanzee, neanderthal and a denisovan hominin identifies novel potentially compensated mutations.	the recent publication of the draft genome sequences of the neanderthal and a ~50,000-year-old archaic hominin from denisova cave in southern siberia has ushered in a new age in molecular archaeology. we previously cross-compared the human, chimpanzee and neanderthal genome sequences with respect to a set of disease-causing/disease-associated missense and regulatory mutations (human gene mutation database) and succeeded in identifying genetic variants which, although apparently pathogenic in hum ...	2011	21807602
Learning about human population history from ancient and modern genomes.	Genome-wide data, both from SNP arrays and from complete genome sequencing, are becoming increasingly abundant and are now even available from extinct hominins. These data are providing new insights into population history; in particular, when combined with model-based analytical approaches, genome-wide data allow direct testing of hypotheses about population history. For example, genome-wide data from both contemporary populations and extinct hominins strongly support a single dispersal of mode ...	2011	21850041
the shaping of modern human immune systems by multiregional admixture with archaic humans.	whole genome comparisons identified introgression from archaic to modern humans. our analysis of highly polymorphic human leukocyte antigen (hla) class i, vital immune system components subject to strong balancing selection, shows how modern humans acquired the hla-b*73 allele in west asia through admixture with archaic humans called denisovans, a likely sister group to the neandertals. virtual genotyping of denisovan and neandertal genomes identified archaic hla haplotypes carrying functionally ...	2011	21868630
paleoanthropology. who were the denisovans?		2011	21868646
paleoanthropology. a denisovan legacy in the immune system?		2011	21868647
denisova admixture and the first modern human dispersals into southeast asia and oceania.	it has recently been shown that ancestors of new guineans and bougainville islanders have inherited a proportion of their ancestry from denisovans, an archaic hominin group from siberia. however, only a sparse sampling of populations from southeast asia and oceania were analyzed. here, we quantify denisova admixture in 33 additional populations from asia and oceania. aboriginal australians, near oceanians, polynesians, fijians, east indonesians, and mamanwa (a "negrito" group from the philippine ...	2011	21944045
archaic human ancestry in east asia.	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 huma ...	2011	22042846
genetic and phenotypic consequences of introgression between humans and neanderthals.	strong evidence for introgression of neanderthal genes into parts of the modern human gene pool has recently emerged. the evidence indicates that some populations of modern humans have received infusions of genes from two different groups of neanderthals. one of these neanderthal groups lived in the middle east and central europe and the other group (the denisovans) is known to have lived in central asia and was probably more widespread. this review examines two questions. first, how were these ...	2011	22099691
paleogenomics of archaic hominins.	in order to understand the genetic basis for the evolutionary success of modern humans, it is necessary to compare their genetic makeup to that of closely related species. unfortunately, our closest living relatives, the chimpanzees, are evolutionarily quite distant. with the advent of ancient dna study and more recently paleogenomics - the study of the genomes of ancient organisms - it has become possible to compare human genomes to those of much more closely related groups. our closest known r ...	2011	22192823
evolution of siglec-11 and siglec-16 genes in hominins.	we previously reported a human-specific gene conversion of siglec11 by an adjacent paralogous pseudogene (siglec16p), generating a uniquely human form of the siglec-11 protein, which is expressed in the human brain. here, we show that siglec-11 is expressed exclusively in microglia in all human brains studied-a finding of potential relevance to brain evolution, as microglia modulate neuronal survival, and siglec-11 recruits shp-1, a tyrosine phosphatase that modulates microglial biology. followi ...	2012	22383531
[adaptive evolution of the homo mitochondrial genome].	adaptive evolution of 12 protein-coding mitochondrial genes in members of genus homo (denisova hominin (h. sp. altai), neandertals (h. neanderthalensis) and modern humans (h. sapiens)) has been evaluated by assessing the pattern of changes in the physicochemical properties of amino acid replacements during the primate evolution. it has been found that in the homo molecular adaptation (positive destabilizing selection) become apparent in the form of 12 radical amino acid replacements accompanied ...	2012	22393781
human evolution out of africa: the role of refugia and climate change.	although an african origin of the modern human species is generally accepted, the evolutionary processes involved in the speciation, geographical spread, and eventual extinction of archaic humans outside of africa are much debated. an additional complexity has been the recent evidence of limited interbreeding between modern humans and the neandertals and denisovans. modern human migrations and interactions began during the buildup to the last glacial maximum, starting about 100,000 years ago. by ...	2012	22422974
specific inactivation of two immunomodulatory siglec genes during human evolution.	sialic acid-recognizing ig-like lectins (siglecs) are signaling receptors that modulate immune responses, and are targeted for interactions by certain pathogens. we describe two primate siglecs that were rendered nonfunctional by single genetic events during hominin evolution after our common ancestor with the chimpanzee. siglec13 was deleted by an alu-mediated recombination event, and a single base pair deletion disrupted the orf of siglec17. siglec-13 is expressed on chimpanzee monocytes, inna ...	2012	22665810
neandertal and denisovan retroviruses.		2012	22677281
the status of homo heidelbergensis (schoetensack 1908).	the species homo heidelbergensis is central to many discussions about recent human evolution. for some workers, it was the last common ancestor for the subsequent species homo sapiens and homo neanderthalensis; others regard it as only a european form, giving rise to the neanderthals. following the impact of recent genomic studies indicating hybridization between modern humans and both neanderthals and "denisovans", the status of these as separate taxa is now under discussion. accordingly, clari ...	2012	22718477
a high-coverage genome sequence from an archaic denisovan individual.	we present a dna library preparation method that has allowed us to reconstruct a high-coverage (30×) genome sequence of a denisovan, an extinct relative of neandertals. the quality of this genome allows a direct estimation of denisovan heterozygosity indicating that genetic diversity in these archaic hominins was extremely low. it also allows tentative dating of the specimen on the basis of "missing evolution" in its genome, detailed measurements of denisovan and neandertal admixture into presen ...	2012	22936568
unexpectedly many extinct hominins.	recent studies indicate that neanderthal and denisova hominins may have been separate species, while debate continues on the status of homo floresiensis. the decade-long debate between "splitters," who recognize over 20 hominin species, and "lumpers," who maintain that all these fossils belong to just a few lineages, illustrates that we do not know how many extinct hominin species to expect. here, we present probability distributions for the number of speciation events and the number of contempo ...	2012	22946817
the apolipoprotein e (apoe) gene appears functionally monomorphic in chimpanzees (pan troglodytes).	the human apolipoprotein e (apoe) gene is polymorphic, with three primary alleles (e2, e3, e4) that differ at two key non-synonymous sites. these alleles are functionally different in how they bind to lipoproteins, and this genetic variation is associated with phenotypic variation for several medical traits, including cholesterol levels, cardiovascular health, alzheimer's disease risk, and longevity. the relative frequencies of these alleles vary across human populations, and the evolution and m ...	2012	23112842
archaic human genomics.	for much of the 20th century, the predominant view of human evolutionary history was derived from the fossil record. homo erectus was seen arising in africa from an earlier member of the genus and then spreading throughout the old world and into the oceania. a regional continuity model of anagenetic change from h. erectus via various intermediate archaic species into the modern humans in each of the regions inhabited by h. erectus was labeled the multiregional model of human evolution (mre). a c ...	2012	23124308
human brain evolution: transcripts, metabolites and their regulators.	what evolutionary events led to the emergence of human cognition? although the genetic differences separating modern humans from both non-human primates (for example, chimpanzees) and archaic hominins (neanderthals and denisovans) are known, linking human-specific mutations to the cognitive phenotype remains a challenge. one strategy is to focus on human-specific changes at the level of intermediate phenotypes, such as gene expression and metabolism, in conjunction with evolutionary changes in g ...	2013	23324662
linking dopamine neurotransmission and neurogenesis: the evolutionary history of the ntad (ncam1-ttc12-ankk1-drd2) gene cluster.	genetic studies have long suggested the important role of the drd2 gene in psychiatric disorders and behavior. further research has shown a conjoined effect of genes in the chr11q22-23 region, which includes the ncam1, ttc12, ankk1 and drd2 genes, or ntad cluster. despite a growing need to unravel the role of this cluster, few studies have taken into account interspecies and evolutionary approaches. this study shows that behaviorally relevant snps from the ntad cluster, such as rs1800497 (taq1a) ...	2012	23412349
hiv infection reveals widespread expansion of novel centromeric human endogenous retroviruses.	human endogenous retroviruses (hervs) make up 8% of the human genome. the herv-k (hml-2) family is the most recent group of these viruses to have inserted into the genome, and we have detected the activation of herv-k (hml-2) proviruses in the blood of patients with hiv-1 infection. we report that hiv-1 infection activates expression of a novel herv-k (hml-2) provirus, termed k111, present in multiple copies in the centromeres of chromosomes throughout the human genome yet not annotated in the m ...	2013	23657884
the genochip: a new tool for genetic anthropology.	the genographic project is an international effort aimed at charting human migratory history. the project is nonprofit and nonmedical, and, through its legacy fund, supports locally led efforts to preserve indigenous and traditional cultures. although the first phase of the project was focused on uniparentally inherited markers on the y-chromosome and mitochondrial dna (mtdna), the current phase focuses on markers from across the entire genome to obtain a more complete understanding of human gen ...	2013	23666864
continuity of microblade technology in the indian subcontinent since 45 ka: implications for the dispersal of modern humans.	we extend the continuity of microblade technology in the indian subcontinent to 45 ka, on the basis of optical dating of microblade assemblages from the site of mehtakheri, (22° 13' 44″ n lat 76° 01' 36″ e long) in madhya pradesh, india. microblade technology in the indian subcontinent is continuously present from its first appearance until the iron age (~3 ka), making its association with modern humans undisputed. it has been suggested that microblade technology in the indian subcontinent was d ...	2013	23840912
neanderthal and denisova genetic affinities with contemporary humans: introgression versus common ancestral polymorphisms.	analyses of the genetic relationships among modern humans, neanderthals and denisovans have suggested that 1-4% of the non-sub-saharan african gene pool may be neanderthal derived, while 6-8% of the melanesian gene pool may be the product of admixture between the denisovans and the direct ancestors of melanesians. in the present study, we analyzed single nucleotide polymorphism (snp) diversity among a worldwide collection of contemporary human populations with respect to the genetic constitution ...	2013	23872234
adaptive introgression in animals: examples and comparison to new mutation and standing variation as sources of adaptive variation.	adaptive genetic variation has been thought to originate primarily from either new mutation or standing variation. another potential source of adaptive variation is adaptive variants from other (donor) species that are introgressed into the (recipient) species, termed adaptive introgression. here, the various attributes of these three potential sources of adaptive variation are compared. for example, the rate of adaptive change is generally thought to be faster from standing variation, slower fr ...	2013	23906376
the cognitive ability of extinct hominins: bringing down the hierarchy using genomic evidences.	the availability of the full genomes of homo sapiens, homo neanderthalensis, and denisovans, as well as modern bioinformatic tools, are opening new possibilities for the understanding of the differences and similarities present in these taxa.	2013	23907779
using the neanderthal and denisova genetic data to understand the common mapt 17q21 inversion in modern humans.	the polymorphic inversion on 17q21, that includes the mapt gene, represents a unique locus in the human genome characterized by a large region with strong linkage disequilibrium. two distinct haplotypes, h1 and h2, exist in modern humans, and h1 has been unequivocally related to several neurodegenerative disorders. recent data indicate that recurrent inversions of this genomic region have occurred through primate evolution, with the h2 haplotype being the ancestral state. neandertals harbored th ...	2012	23959642
hominin evolution and gene flow in the pleistocene africa.	africa demonstrates a complex process of the hominin evolution with a series of adaptive radiations during several millions of years that led to diverse morphological forms. recently, hammer et al. (2011) and harvati et al. (2011) provided integrated morphological and genetic evidence of interbreeding between modern humans and unknown archaic hominins in africa as recently as 35,000 years ago. however, a genetic evidence of hybridization between hominin lineages during the lower and middle pleis ...	2013	23980394
paleontology. did the denisovans cross wallace's line?		2013	24136958
neanderthal and denisovan retroviruses in modern humans.		2013	24262833
introduction: revisiting the "negrito" hypothesis: a transdisciplinary approach to human prehistory in southeast asia.	the "negrito" hypothesis predicts that a shared phenotype among various contemporary groups of hunter-gatherers in southeast asia--dark skin, short stature, tight curly hair--is due to common descent from a region-wide, pre-neolithic substrate of humanity. the alternative is that their distinctive phenotype results from convergent evolution. the core issues of the negrito hypothesis are today more relevant than ever to studies of human evolution, including the out-of-africa migration, admixture ...	2013	24297218
hunter-gatherers in southeast asia: from prehistory to the present.	anatomically modern hunter-gatherers expanded from africa into southeast asia at least 50,000 years ago, where they probably encountered and interacted with populations of homo erectus and homo floresiensis and the recently discovered denisovans. simulation studies suggest that these hunter-gatherers may well have followed a coastal route that ultimately led to the settlement of sahul, while archaeology confirms that they also crossed significant seas and explored well into the interior. they al ...	2013	24297219
a mitochondrial genome sequence of a hominin from sima de los huesos.	excavations of a complex of caves in the sierra de atapuerca in northern spain have unearthed hominin fossils that range in age from the early pleistocene to the holocene. one of these sites, the 'sima de los huesos' ('pit of bones'), has yielded the world's largest assemblage of middle pleistocene hominin fossils, consisting of at least 28 individuals dated to over 300,000 years ago. the skeletal remains share a number of morphological features with fossils classified as homo heidelbergensis an ...	2014	24305051
human evolution. elusive denisovans sighted in oldest human dna.		2013	24311652
neanderthal introgression at chromosome 3p21.31 was under positive natural selection in east asians.	studies of the neanderthal and denisovan genomes demonstrate archaic hominin introgression in eurasians. here, we present evidence of neanderthal introgression within the chromosome 3p21.31 region, occurring with a high frequency in east asians (ranging from 49.4% to 66.5%) and at a low frequency in europeans. we also detected a signal of strong positive selection in this region only in east asians. our data indicate that likely candidate targets of selection include rs12488302-t and its associa ...	2014	24336922
identification of putative target genes of the transcription factor runx2.	comparisons of the genomes of neandertals and denisovans with present-day human genomes have suggested that the gene runx2, which encodes a transcription factor, may have been positively selected during early human evolution. here, we overexpress runx2 in ten human cell lines and identify genes that are directly or indirectly affected by runx2 expression. we find a number of genes not previously known to be affected by runx2 expression, in particular birc3, genes encoded on the mitochondrial gen ...	2013	24349465
the complete genome sequence of a neanderthal from the altai mountains.	we present a high-quality genome sequence of a neanderthal woman from siberia. we show that her parents were related at the level of half-siblings and that mating among close relatives was common among her recent ancestors. we also sequenced the genome of a neanderthal from the caucasus to low coverage. an analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among neanderthals, denisovans a ...	2014	24352235
a penile spine/vibrissa enhancer sequence is missing in modern and extinct humans but is retained in multiple primates with penile spines and sensory vibrissae.	previous studies show that humans have a large genomic deletion downstream of the androgen receptor gene that eliminates an ancestral mammalian regulatory enhancer that drives expression in developing penile spines and sensory vibrissae. here we use a combination of large-scale sequence analysis and pcr amplification to demonstrate that the penile spine/vibrissa enhancer is missing in all humans surveyed and in the neandertal and denisovan genomes, but is present in dna samples of chimpanzees an ...	2013	24367647
loss of olfactory receptor function in hominin evolution.	the mammalian sense of smell is governed by the largest gene family, which encodes the olfactory receptors (ors). the gain and loss of or genes is typically correlated with adaptations to various ecological niches. modern humans have 853 or genes but 55% of these have lost their function. here we show evidence of additional or loss of function in the neanderthal and denisovan hominin genomes using comparative genomic methodologies. ten neanderthal and 8 denisovan ors show evidence of loss of fun ...	2014	24392153
pseudogenization of testis-specific lfg5 predates human/neanderthal divergence.	recent reviews discussed the critical roles of apoptosis in human spermatogenesis and infertility. these reviews highlight the fasl-induced caspase cascade in apoptosis lending importance to our discovery of the pseudogene status of the lfg5 gene in modern humans, neanderthal and the denisovan. this gene is a member of the ancient and highly conserved apoptosis lifeguard family. this pseudogenization is the result of a premature stop codon at the 3'-end of exon 8 not found in any other ortholog. ...	2014	24599118
searching for signatures of cold adaptations in modern and archaic humans: hints from the brown adipose tissue genes.	adaptation to low temperatures has been reasonably developed in the human species during the colonization of the eurasian landmass subsequent to out of africa migrations of anatomically modern humans. in addition to morphological and cultural changes, also metabolic ones are supposed to have favored human isolation from cold and body heat production and this can be hypothesized also for most neandertal and at least for some denisovan populations, which lived in geographical areas that strongly e ...	2014	24667833
a 400,000-year-old mitochondrial genome questions phylogenetic relationships amongst archaic hominins: using the latest advances in ancient genomics, the mitochondrial genome sequence of a 400,000-year-old hominin has been deciphered.	by combining state-of-the-art approaches in ancient genomics, meyer and co-workers have reconstructed the mitochondrial sequence of an archaic hominin that lived at sierra de atapuerca, spain about 400,000 years ago. this achievement follows recent advances in molecular anthropology that delivered the genome sequence of younger archaic hominins, such as neanderthals and denisovans. molecular phylogenetic reconstructions placed the atapuercan as a sister group to denisovans, although its morpholo ...	2014	24706482
the shape of the human language-ready brain.	our core hypothesis is that the emergence of our species-specific language-ready brain ought to be understood in light of the developmental changes expressed at the levels of brain morphology and neural connectivity that occurred in our species after the split from neanderthals-denisovans and that gave us a more globular braincase configuration. in addition to changes at the cortical level, we hypothesize that the anatomical shift that led to globularity also entailed significant changes at the ...	2014	24772099
reconstructing the dna methylation maps of the neandertal and the denisovan.	ancient dna sequencing has recently provided high-coverage archaic human genomes. however, the evolution of epigenetic regulation along the human lineage remains largely unexplored. we reconstructed the full dna methylation maps of the neandertal and the denisovan by harnessing the natural degradation processes of methylated and unmethylated cytosines. comparing these ancient methylation maps to those of present-day humans, we identified ~2000 differentially methylated regions (dmrs). particular ...	2014	24786081
insights into the genetic structure and diversity of 38 south asian indians from deep whole-genome sequencing.	south asia possesses a significant amount of genetic diversity due to considerable intergroup differences in culture and language. there have been numerous reports on the genetic structure of asian indians, although these have mostly relied on genotyping microarrays or targeted sequencing of the mitochondria and y chromosomes. asian indians in singapore are primarily descendants of immigrants from dravidian-language-speaking states in south india, and 38 individuals from the general population u ...	2014	24832686
did neanderthals and denisovans have our de novo genes?		2014	24952670
primate evolution of the recombination regulator prdm9.	the prdm9 gene encodes a protein with a highly variable tandem-repeat zinc finger (zf) dna-binding domain that plays a key role in determining sequence-specific hotspots of meiotic recombination genome wide. here we survey the diversity of the prdm9 zf domain by sequencing this region in 64 primates from 18 species, revealing 68 unique alleles across all groups. we report ubiquitous positive selection at nucleotide positions corresponding to dna contact residues and the expansion of zfs within c ...	2014	25001002
altitude adaptation in tibetans caused by introgression of denisovan-like dna.	as modern humans migrated out of africa, they encountered many new environmental conditions, including greater temperature extremes, different pathogens and higher altitudes. these diverse environments are likely to have acted as agents of natural selection and to have led to local adaptations. one of the most celebrated examples in humans is the adaptation of tibetans to the hypoxic environment of the high-altitude tibetan plateau. a hypoxia pathway gene, epas1, was previously identified as hav ...	2014	25043035
novel denisovan and neanderthal retroviruses.	following the recent availability of high-coverage genomes for denisovan and neanderthal hominids, we conducted a screen for endogenized retroviruses, identifying six novel, previously unreported herv-k(hml2) elements (herv-k is human endogenous retrovirus k). these elements are absent from the human genome (hg38) and appear to be unique to archaic hominids. these findings provide further evidence supporting the recent activity of the herv-k(hml2) group, which has been implicated in human diseas ...	2014	25142605
a test for ancient selective sweeps and an application to candidate sites in modern humans.	we introduce a new method to detect ancient selective sweeps centered on a candidate site. we explored different patterns produced by sweeps around a fixed beneficial mutation, and found that a particularly informative statistic measures the consistency between majority haplotypes near the mutation and genotypic data from a closely related population. we incorporated this statistic into an approximate bayesian computation (abc) method that tests for sweeps at a candidate site. we applied this me ...	2014	25172957
preserving immune diversity through ancient inheritance and admixture.	the progress of genomic technologies is allowing researchers to scan the genomes of different species for the occurrence of natural selection at an unprecedented level of resolution. these studies show that genes involved in immune processes are preferential targets of different forms of selection, some of which act to preserve immune diversity over time. recent work in humans shows that this can be achieved either by inheriting advantageous immune variation from distant ancestral species, throu ...	2014	25190608
the evolution of cancer-related genes in hominoids.	the evolution of cancer suppression is essential for the maintenance of multicellularity. the lack of correlation between body size and cancer risk across species, known as peto's paradox, suggests that genetic variation in cancer resistance is sufficient to compensate for increases of cell numbers in bigger animals. to assess evolutionary dynamics of cancer-related genes, we analyzed ka, ks,and ka/ks values in 120 oncogenes and tumor suppressor genes (tsg) among seven hominoid species, includin ...	2015	25249249
epigenetic information from ancient dna provides new insights into human evolution. commentary on gokhman d et al. (2014): reconstructing the dna methylation maps of the neanderthal and the denisovan. science 344:523-527.		2014	25277105
ancient humans and the origin of modern humans.	recent advances in sequencing technologies and molecular methods have facilitated the sequencing of dna from ancient human remains which has, in turn, provided unprecedented insight into human history. within the past 4 years the genomes of neandertals and denisovans, as well as the genomes of at least two early modern humans, have been sequenced. these sequences showed that there have been several episodes of admixture between modern and archaic groups; including admixture from neandertals into ...	2014	25286439
the red queen model of recombination hotspots evolution in the light of archaic and modern human genomes.	recombination is an essential process in eukaryotes, which increases diversity by disrupting genetic linkage between loci and ensures the proper segregation of chromosomes during meiosis. in the human genome, recombination events are clustered in hotspots, whose location is determined by the prdm9 protein. there is evidence that the location of hotspots evolves rapidly, as a consequence of changes in prdm9 dna-binding domain. however, the reasons for these changes and the rate at which they occu ...	2014	25393762
leukotriene signaling in the extinct human subspecies homo denisovan and homo neanderthalensis. structural and functional comparison with homo sapiens.	mammalian lipoxygenases (loxs) have been implicated in cell differentiation and in the biosynthesis of pro- and anti-inflammatory lipid mediators. the initial draft sequence of the homo neanderthalensis genome (coverage of 1.3-fold) suggested defective leukotriene signaling in this archaic human subspecies since expression of essential proteins appeared to be corrupted. meanwhile high quality genomic sequence data became available for two extinct human subspecies (h. neanderthalensis, homo denis ...	2015	25447821
[mitochondrial dna polymorphisms shared between modern humans and neanderthals: adaptive convergence or evidence for interspecific hybridization?].	an analysis of the variability of the nucleotide sequences in the mitochondrial genome of modern humans, neanderthals, denisovans, and other primates has shown that there are shared polymorphisms at positions 2758 and 7146 between modern homo sapiens (in phylogenetic cluster l2'3'4'5'6) and homo neanderthalensis (in the group of european neanderthals younger than 48000 years). it is suggested that the convergence may be due to adaptive changes in the mitochondrial genomes of modern humans and ne ...	2013	25486780
almost 20 years of neanderthal palaeogenetics: adaptation, admixture, diversity, demography and extinction.	nearly two decades since the first retrieval of neanderthal dna, recent advances in next-generation sequencing technologies have allowed the generation of high-coverage genomes from two archaic hominins, a neanderthal and a denisovan, as well as a complete mitochondrial genome from remains which probably represent early members of the neanderthal lineage. this genomic information, coupled with diversity exome data from several neanderthal specimens is shedding new light on evolutionary processes ...	2015	25487326
[mitochondrial dna polymorphisms shared between modern humans and neanderthals: adaptive convergence or evidence for interspecific hybridization?].	an analysis of the variability of the nucleotide sequences in the mitochondrial genome of modern humans, neanderthals, denisovans, and other primates has shown that there are shared polymorphisms at positions 2758 and 7146 between modern homo sapiens (in phylogenetic cluster l2'3'4'5'6) and homo neanderthalensis (in the group of european neanderthals younger than 48000 years). it is suggested that the convergence may be due to adaptive changes in the mitochondrial genomes of modern humans and ne ...	2013	25508911
[mutation process in the protein-coding genes of human mitochondrial genome in context of evolution of the genus].	the human mitochondrial genome, although it has a small size, is characterized by high level of variation, non-uniformly distributed in groups of nucleotide positions that differ in the degree of variability. considering the mutation process in human mtdna relative to the mitochondrial genomes of the genus homo-neandertals, denisova hominin and other primate species, it appears that more than half (56.5%) variable positions in the human mtdna protein-coding genes are characterized by back (rever ...	2014	25509854
the evolution and functional impact of human deletion variants shared with archaic hominin genomes.	allele sharing between modern and archaic hominin genomes has been variously interpreted to have originated from ancestral genetic structure or through non-african introgression from archaic hominins. however, evolution of polymorphic human deletions that are shared with archaic hominin genomes has yet to be studied. we identified 427 polymorphic human deletions that are shared with archaic hominin genomes, approximately 87% of which originated before the human-neandertal divergence (ancient) an ...	2015	25556237
insights into hominin phenotypic and dietary evolution from ancient dna sequence data.	nuclear genome sequence data from neandertals, denisovans, and archaic anatomically modern humans can be used to complement our understanding of hominin evolutionary biology and ecology through i) direct inference of archaic hominin phenotypes, ii) indirect inference of those phenotypes by identifying the effects of previously-introgressed alleles still present among modern humans, or iii) determining the evolutionary timing of relevant hominin-specific genetic changes. here we review and reanal ...	2015	25563409
bias in estimators of archaic admixture.	this article evaluates bias in one class of methods used to estimate archaic admixture in modern humans. these methods study the pattern of allele sharing among modern and archaic genomes. they are sensitive to "ghost" admixture, which occurs when a population receives archaic dna from sources not acknowledged by the statistical model. the effect of ghost admixture depends on two factors: branch-length bias and population-size bias. branch-length bias occurs because a given amount of admixture h ...	2015	25575941
no evidence that selection has been less effective at removing deleterious mutations in europeans than in africans.	non-african populations have experienced size reductions in the time since their split from west africans, leading to the hypothesis that natural selection to remove weakly deleterious mutations has been less effective in the history of non-africans. to test this hypothesis, we measured the per-genome accumulation of nonsynonymous substitutions across diverse pairs of populations. we find no evidence for a higher load of deleterious mutations in non-africans. however, we detect significant diffe ...	2015	25581429
the diverse origins of the human gene pool.	analyses of the genomes of neanderthals and denisovans, the closest evolutionary relatives of present-day humans, suggest that our ancestors were part of a web of now-extinct populations linked by limited, but intermittent or sometimes perhaps even persistent, gene flow.	2015	25982166
mapping the space of genomic signatures.	we propose a computational method to measure and visualize interrelationships among any number of dna sequences allowing, for example, the examination of hundreds or thousands of complete mitochondrial genomes. an "image distance" is computed for each pair of graphical representations of dna sequences, and the distances are visualized as a molecular distance map: each point on the map represents a dna sequence, and the spatial proximity between any two points reflects the degree of structural si ...	2015	26000734
global survey of variation in a human olfactory receptor gene reveals signatures of non-neutral evolution.	allelic variation at 4 loci in the human olfactory receptor gene or7d4 is associated with perceptual variation in the sex steroid-derived odorants, androstenone, and androstadienone. androstadienone has been linked with chemosensory identification whereas androstenone makes pork from uncastrated pigs distasteful ("boar taint"). in a sample of 2224 individuals from 43 populations, we identified 45 or7d4 single nucleotide polymorphisms. coalescent modeling of frequency-site-spectrum-based statisti ...	2015	26072518
a 3.4-kb copy-number deletion near epas1 is significantly enriched in high-altitude tibetans but absent from the denisovan sequence.	tibetan high-altitude adaptation (haa) has been studied extensively, and many candidate genes have been reported. subsequent efforts targeting haa functional variants, however, have not been that successful (e.g., no functional variant has been suggested for the top candidate haa gene, epas1). with winxpcnver, a method developed in this study, we detected in microarray data a tibetan-enriched deletion (ted) carried by 90% of tibetans; 50% were homozygous for the deletion, whereas only 3% carried ...	2015	26073780
denisovan ancestry in east eurasian and native american populations.	although initial studies suggested that denisovan ancestry was found only in modern human populations from island southeast asia and oceania, more recent studies have suggested that denisovan ancestry may be more widespread. however, the geographic extent of denisovan ancestry has not been determined, and moreover the relationship between the denisovan ancestry in oceania and that elsewhere has not been studied. here we analyze genome-wide single nucleotide polymorphism data from 2,493 individua ...	2015	26104010
possible functional links among brain- and skull-related genes selected in modern humans.	the sequencing of the genomes from extinct hominins has revealed that changes in some brain-related genes have been selected after the split between anatomically-modern humans and neanderthals/denisovans. to date, no coherent view of these changes has been provided. following a line of research we initiated in boeckx and benítez-burraco (2014a), we hypothesize functional links among most of these genes and their products, based on the existing literature for each of the gene discussed. the genes ...	2015	26136701
contrasted patterns of variation and evolutionary convergence at the antiviral oas1 gene in old world primates.	the oligoadenylate synthetase 1 (oas1) enzyme acts as an innate sensor of viral infection and plays a major role in the defense against a wide diversity of viruses. polymorphisms at oas1 have been shown to correlate with differential susceptibility to several infections of great public health significance, including hepatitis c virus, sars coronavirus, and west nile virus. population genetics analyses in hominoids have revealed interesting evolutionary patterns. in central african chimpanzee, oa ...	2015	26156123
distribution of hla haplotypes across japanese archipelago: similarity, difference and admixture.	the human leukocyte antigen (hla) region is the most polymorphic region in the human genome. the polymorphic nature of the hla region is thought to have been shaped from balancing selection. the complex migration events during the out-of-africa expansion have influenced geographic patterns of hla allele frequencies and diversities across present-day human populations. differences in the hla allele frequency may contribute geographic differences in the susceptibility to many diseases, such as inf ...	2015	26202576
all-or-(n)one - an epistemological characterization of the human tumorigenic neuronal paralogous fam72 gene loci.	fam72 is a novel neuronal progenitor cell (npc) self-renewal supporting protein expressed under physiological conditions at low levels in other tissues. accumulating data indicate the potential pivotal tumourigenic effects of fam72. our in silico human genome-wide analysis (gwa) revealed that the fam72 gene family consists of four human-specific paralogous members, all of which are located on chromosome (chr) 1. unique asymmetric fam72 segmental gene duplications are most likely to have occurred ...	2015	26206078
archaic inheritance: supporting high-altitude life in tibet.	the tibetan plateau, often called the roof of the world, sits at an average altitude exceeding 4,500 m. because of its extreme altitude, the plateau is one of the harshest human-inhabited environments in the world. this, however, did not impede human colonization, and the tibetan people have made the tibetan plateau their home for many generations. many studies have quantified their markedly different physiological response to altitude and proposed that tibetans were genetically adapted. recentl ...	2015	26294746
human evolution. cave was lasting home to denisovans.		2015	26383930
chromosomal rearrangements as barriers to genetic homogenization between archaic and modern humans.	chromosomal rearrangements, which shuffle dna throughout the genome, are an important source of divergence across taxa. using a paired-end read approach with illumina sequence data for archaic humans, i identify changes in genome structure that occurred recently in human evolution. hundreds of rearrangements indicate genomic trafficking between the sex chromosomes and autosomes, raising the possibility of sex-specific changes. additionally, genes adjacent to genome structure changes in neanderth ...	2015	26399483
brain asymmetry in the white matter making and globularity.	recent studies from the field of language genetics and evolutionary anthropology have put forward the hypothesis that the emergence of our species-specific brain is to be understood not in terms of size, but in light of developmental changes that gave rise to a more globular braincase configuration after the split from neanderthals-denisovans. on the grounds that (i) white matter myelination is delayed relative to other brain structures and, in humans, is protracted compared with other primates ...	2015	26441731
small amounts of archaic admixture provide big insights into human history.	modern humans overlapped in time and space with other hominins, such as neanderthals and denisovans, and limited amounts of hybridization occurred. here, we review recent work that has identified archaic hominin sequence that survives in modern human genomes and what these genomic excavations reveal about human evolutionary history.	2015	26451479
functional analyses of transcription factor binding sites that differ between present-day and archaic humans.	we analyze 25 previously identified transcription factor binding sites that carry dna sequence changes that are present in all or nearly all present-day humans, yet occur in the ancestral state in neandertals and denisovans, the closest evolutionary relatives of humans. when the ancestral and derived forms of the transcription factor binding sites are tested using reporter constructs in 3 neuronal cell lines, the activity of 12 of the derived versions of transcription factor binding sites differ ...	2016	26454764
bayesian analyses of yemeni mitochondrial genomes suggest multiple migration events with africa and western eurasia.	anatomically, modern humans are thought to have migrated out of africa ∼60,000 years ago in the first successful global dispersal. this initial migration may have passed through yemen, a region that has experienced multiple migrations events with africa and eurasia throughout human history. we use bayesian phylogenetics to determine how ancient and recent migrations have shaped yemeni mitogenomic variation.	2016	26567083
nuclear and mitochondrial dna sequences from two denisovan individuals.	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, fro ...	2015	26630009
deciphering the denisovans.		2015	26668361
the evolution of homo sapiens denisova and homo sapiens neanderthalensis mirna targeting genes in the prenatal and postnatal brain.	as the evolution of mirna genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of mirna genes in two archaic hominines, homo sapiens neanderthalensis and homo sapiens denisova, and elucidated the expression of their target mrnas in bain.	2015	26693966
the "globularization hypothesis" of the language-ready brain as a developmental frame for prosodic bootstrapping theories of language acquisition.	in recent research (boeckx and benítez-burraco, 2014a,b) have advanced the hypothesis that our species-specific language-ready brain should be understood as the outcome of developmental changes that occurred in our species after the split from neanderthals-denisovans, which resulted in a more globular braincase configuration in comparison to our closest relatives, who had elongated endocasts. according to these authors, the development of a globular brain is an essential ingredient for the langu ...	2015	26696916
genes regulated by vitamin d in bone cells are positively selected in east asians.	vitamin d and folate are activated and degraded by sunlight, respectively, and the physiological processes they control are likely to have been targets of selection as humans expanded from africa into eurasia. we investigated signals of positive selection in gene sets involved in the metabolism, regulation and action of these two vitamins in worldwide populations sequenced by phase i of the 1000 genomes project. comparing allele frequency-spectrum-based summary statistics between these gene sets ...	2015	26719974
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 ...	2016	26748514
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 ...	2016	26791510
wide distribution and altitude correlation of an archaic high-altitude-adaptive epas1 haplotype in the himalayas.	high-altitude adaptation in tibetans is influenced by introgression of a 32.7-kb haplotype from the denisovans, an extinct branch of archaic humans, lying within the endothelial pas domain protein 1 (epas1), and has also been reported in sherpa. we genotyped 19 variants in this genomic region in 1507 eurasian individuals, including 1188 from bhutan and nepal residing at altitudes between 86 and 4550 m above sea level. derived alleles for five snps characterizing the core denisovan haplotype (agg ...	2016	26883865
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.	2016	26885854
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 ...	2016	26886800
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 ...	2016	26888264
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 ...	2016	26898827
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 ...	2016	26912479
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 ...	2016	26912899