Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not ...present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.
Northeastern Siberia has been inhabited by humans for more than 40,000 years but its deep population history remains poorly understood. Here we investigate the late Pleistocene population history of ...northeastern Siberia through analyses of 34 newly recovered ancient genomes that date to between 31,000 and 600 years ago. We document complex population dynamics during this period, including at least three major migration events: an initial peopling by a previously unknown Palaeolithic population of 'Ancient North Siberians' who are distantly related to early West Eurasian hunter-gatherers; the arrival of East Asian-related peoples, which gave rise to 'Ancient Palaeo-Siberians' who are closely related to contemporary communities from far-northeastern Siberia (such as the Koryaks), as well as Native Americans; and a Holocene migration of other East Asian-related peoples, who we name 'Neo-Siberians', and from whom many contemporary Siberians are descended. Each of these population expansions largely replaced the earlier inhabitants, and ultimately generated the mosaic genetic make-up of contemporary peoples who inhabit a vast area across northern Eurasia and the Americas.
In order to explore the diversity and selective signatures of duplication and deletion human copy-number variants (CNVs), we sequenced 236 individuals from 125 distinct human populations. We observed ...that duplications exhibit fundamentally different population genetic and selective signatures than deletions and are more likely to be stratified between human populations. Through reconstruction of the ancestral human genome, we identify megabases of DNA lost in different human lineages and pinpoint large duplications that introgressed from the extinct Denisova lineage now found at high frequency exclusively in Oceanic populations. We find that the proportion of CNV base pairs to single-nucleotide-variant base pairs is greater among non-Africans than it is among African populations, but we conclude that this difference is likely due to unique aspects of non-African population history as opposed to differences in CNV load.
European population history has been shaped by migrations of people, and their subsequent admixture. Recently, ancient DNA has brought new insights into European migration events linked to the advent ...of agriculture, and possibly to the spread of Indo-European languages. However, little is known about the ancient population history of north-eastern Europe, in particular about populations speaking Uralic languages, such as Finns and Saami. Here we analyse ancient genomic data from 11 individuals from Finland and north-western Russia. We show that the genetic makeup of northern Europe was shaped by migrations from Siberia that began at least 3500 years ago. This Siberian ancestry was subsequently admixed into many modern populations in the region, particularly into populations speaking Uralic languages today. Additionally, we show that ancestors of modern Saami inhabited a larger territory during the Iron Age, which adds to the historical and linguistic information about the population history of Finland.
Mitochondrial dysfunction affects cellular energy metabolism, but less is known about the consequences for cytoplasmic biosynthetic reactions. We report that mtDNA replication disorders caused by ...TWINKLE mutations—mitochondrial myopathy (MM) and infantile onset spinocerebellar ataxia (IOSCA)—remodel cellular dNTP pools in mice. MM muscle shows tissue-specific induction of the mitochondrial folate cycle, purine metabolism, and imbalanced and increased dNTP pools, consistent with progressive mtDNA mutagenesis. IOSCA-TWINKLE is predicted to hydrolyze dNTPs, consistent with low dNTP pools and mtDNA depletion in the disease. MM muscle also modifies the cytoplasmic one-carbon cycle, transsulfuration, and methylation, as well as increases glucose uptake and its utilization for de novo serine and glutathione biosynthesis. Our evidence indicates that the mitochondrial replication machinery communicates with cytoplasmic dNTP pools and that upregulation of glutathione synthesis through glucose-driven de novo serine biosynthesis contributes to the metabolic stress response. These results are important for disorders with primary or secondary mtDNA instability and offer targets for metabolic therapy.
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•mtDNA replication dysfunction disturbs the cellular folate-driven one-carbon cycle•mtDNA depletion disorders show low and imbalanced dNTP pools•Multiple mtDNA deletion disorders show imbalanced and high dNTP pools•De novo serine biosynthesis drives glutathione production in mitochondrial disease
Nikkanen et al. report that mtDNA replication defects induce a cell-autonomous metabolic stress response in mice, with a widespread imbalance of folate-dependent biosynthetic pathways, including mutagenic dNTP pools, upregulated de novo serine and glutathione synthesis, and deficient metabolite methylation. One-carbon metabolic remodeling is also observed in human patients.
Smallpox holds a unique position in the history of medicine. It was the first disease for which a vaccine was developed and remains the only human disease eradicated by vaccination. Although there ...have been claims of smallpox in Egypt, India, and China dating back millennia 1–4, the timescale of emergence of the causative agent, variola virus (VARV), and how it evolved in the context of increasingly widespread immunization, have proven controversial 4–9. In particular, some molecular-clock-based studies have suggested that key events in VARV evolution only occurred during the last two centuries 4–6 and hence in apparent conflict with anecdotal historical reports, although it is difficult to distinguish smallpox from other pustular rashes by description alone. To address these issues, we captured, sequenced, and reconstructed a draft genome of an ancient strain of VARV, sampled from a Lithuanian child mummy dating between 1643 and 1665 and close to the time of several documented European epidemics 1, 2, 10. When compared to vaccinia virus, this archival strain contained the same pattern of gene degradation as 20th century VARVs, indicating that such loss of gene function had occurred before ca. 1650. Strikingly, the mummy sequence fell basal to all currently sequenced strains of VARV on phylogenetic trees. Molecular-clock analyses revealed a strong clock-like structure and that the timescale of smallpox evolution is more recent than often supposed, with the diversification of major viral lineages only occurring within the 18th and 19th centuries, concomitant with the development of modern vaccination.
•Variola virus genome was reconstructed from a 17th century mummified child•The archival strain is basal to all 20th century strains, with same gene degradation•Molecular-clock analyses show that much of variola virus evolution occurred recently
Using ancient DNA sequences of variola virus recovered from the mummified remains of a 17th century child, Duggan et al. reconstruct the evolutionary history of smallpox. With the ancient strain, the genetic diversification of the smallpox virus is found to be more recent than previously supposed and concurrent with the onset of widespread vaccination.
Ten millennia of hepatitis B virus evolution Barquera, Rodrigo; Rohrlach, Adam B; Aron, Franziska ...
Science (American Association for the Advancement of Science),
2021-Oct-08, Volume:
374, Issue:
6564
Journal Article
Peer reviewed
Open access
Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data ...from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for ~4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic.
We assessed the distribution of SARS-CoV-2 at autopsy in 22 deceased persons with confirmed COVID-19. SARS-CoV-2 was found by PCR (2/22, 9.1%) and by culture (1/22, 4.5%) in skull sawdust, suggesting ...that live virus is present in tissues postmortem, including bone. Occupational exposure risk is low with appropriate personal protective equipment.We assessed the distribution of SARS-CoV-2 at autopsy in 22 deceased persons with confirmed COVID-19. SARS-CoV-2 was found by PCR (2/22, 9.1%) and by culture (1/22, 4.5%) in skull sawdust, suggesting that live virus is present in tissues postmortem, including bone. Occupational exposure risk is low with appropriate personal protective equipment.
Background:
The reduction of child and adolescent deaths (defined as decedents aged 0–19 years) remains a crucial public health priority also in high-income countries such as Finland. There is ...evidence of a relationship between socioeconomic gradients and child mortality, but the association is considered complex and relatively poorly understood. Exploiting a Finnish dataset with nationwide coverage, the present study aimed to shed light on the sociodemographic predictors of child and adolescent mortality at the municipality level.
Methods:
A public database of Statistics Finland was queried for municipality-level data on sociodemographic traits and child and adolescent deaths in Finland during the years 2011–2018. The sociodemographic indicators included total population size, child and adolescent population size, sex distribution, mean age, education, unemployment, median income, population density, rurality, percentage of individuals living in their birth municipality, household size, overcrowded households, foreign language speakers, divorce rate, car ownership rate, and crime rate. The sociodemographic indicators were modeled against child and adolescent mortality by means of generalized estimating equations.
Results:
A total of 2,371 child and adolescent deaths occurred during the 8-year study period, yielding an average annual mortality rate of 26.7 per 100,000 individuals. Despite a fluctuating trend, the average annual decline in child and adolescent deaths was estimated to be 3% (95% confidence interval 1–5%). Of the sociodemographic indicators, population density was associated with higher child and adolescent mortality (rate ratio 1.03, 95% confidence interval 1.01–1.06), whereas the percentage of foreign language speakers was associated with lower child and adolescent mortality (0.96, 0.93–0.99).
Conclusion:
Densely populated areas should be the primary focus of efforts to reduce child and adolescent mortality. Of note is also the apparently protective effect of foreign language speakers for premature mortality. Future studies are welcomed to scrutinize the mediating pathways and individual-level factors behind the associations detected in this study.
Abstract In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci ...(DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.
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