Flores Island, Indonesia, was inhabited by the small-bodied hominin species
, which has an unknown evolutionary relationship to modern humans. This island is also home to an extant human pygmy ...population. Here we describe genome-scale single-nucleotide polymorphism data and whole-genome sequences from a contemporary human pygmy population living on Flores near the cave where
was found. The genomes of Flores pygmies reveal a complex history of admixture with Denisovans and Neanderthals but no evidence for gene flow with other archaic hominins. Modern individuals bear the signatures of recent positive selection encompassing the FADS (fatty acid desaturase) gene cluster, likely related to diet, and polygenic selection acting on standing variation that contributed to their short-stature phenotype. Thus, multiple independent instances of hominin insular dwarfism occurred on Flores.
This study aimed to evaluate the association of SNPs of the IL-1 family with the clinical severity of knee OA. This case‒control study was performed among 100 healthy knees and 130 osteoarthritis ...(OA) knees of people aged ≥ 50 years with a BMI ≥ 25 kg/m
. The possible correlations among clinical findings, radiographic evaluations, serum levels of IL-1R1 and IL-1Ra, and genotype analyses were evaluated. Three SNPs of IL-1R1, rs871659, rs3771202, and rs3917238, were associated with primary knee OA. Females with IL-1R1 SNP rs871659 allele A had a higher prevalence of primary knee OA. No correlation was found between SNPs of IL-1R1 and IL-1RN and clinical or radiologic severity or serum concentrations of IL-1R1 and IL-1Ra (p > 0.05). BMI and IL-1R1 rs3917238 genotype C/C were correlated with moderate-severe VAS scores. A correlation was also found between the EQ-5D-3L self-care dimension and obesity and between the EQ-5D-3L pain and usual activity dimensions and age ≥ 60 and obesity (p < 0.05). Radiologic severity was only associated with age ≥ 60 years (p < 0.05). We found the IL-1R1 SNPs rs871659, rs3771202, and rs3917238 to be predisposing factors for primary knee osteoarthritis. The clinical findings, radiographic severity, and serum concentrations of IL-1R1 and IL-1Ra were not correlated with these gene polymorphisms.
Indonesia, an island nation linking mainland Asia with the Pacific world, hosts a wide range of linguistic, ethnic and genetic diversity. Despite the complexity of this cultural environment, genetic ...studies in Indonesia remain surprisingly sparse. Here, we report mitochondrial DNA (mtDNA) and associated Y-chromosome diversity for the largest cohort of Indonesians examined to date-2740 individuals from 70 communities spanning 12 islands across the breadth of the Indonesian archipelago. We reconstruct 50 000 years of population movements, from mitochondrial lineages reflecting the very earliest settlers in island southeast Asia, to Neolithic population dispersals. Historic contacts from Chinese, Indians, Arabs and Europeans comprise a noticeable fraction of Y-chromosome variation, but are not reflected in the maternally inherited mtDNA. While this historic immigration favored men, patterns of genetic diversity show that women moved more widely in earlier times. However, measures of population differentiation signal that Indonesian communities are trending away from the matri- or ambilocality of early Austronesian societies toward the more common practice of patrilocal residence today. Such sex-specific dispersal patterns remain even after correcting for the different mutation rates of mtDNA and the Y chromosome. This detailed palimpsest of Indonesian genetic diversity is a direct outcome of the region's complex history of immigration, transitory migrants and populations that have endured in situ since the region's first settlement.
Primaquine is the only widely used drug that prevents Plasmodium vivax malaria relapses, but adherence to the standard 14-day regimen is poor. We aimed to assess the efficacy of a shorter course (7 ...days) of primaquine for radical cure of vivax malaria.
We did a randomised, double-blind, placebo-controlled, non-inferiority trial in eight health-care clinics (two each in Afghanistan, Ethiopia, Indonesia, and Vietnam). Patients (aged ≥6 months) with normal glucose-6-phosphate dehydrogenase (G6PD) and presenting with uncomplicated vivax malaria were enrolled. Patients were given standard blood schizontocidal treatment and randomly assigned (2:2:1) to receive 7 days of supervised primaquine (1·0 mg/kg per day), 14 days of supervised primaquine (0·5 mg/kg per day), or placebo. The primary endpoint was the incidence rate of symptomatic P vivax parasitaemia during the 12-month follow-up period, assessed in the intention-to-treat population. A margin of 0·07 recurrences per person-year was used to establish non-inferiority of the 7-day regimen compared with the 14-day regimen. This trial is registered at ClinicalTrials.gov (NCT01814683).
Between July 20, 2014, and Nov 25, 2017, 2336 patients were enrolled. The incidence rate of symptomatic recurrent P vivax malaria was 0·18 (95% CI 0·15 to 0·21) recurrences per person-year for 935 patients in the 7-day primaquine group and 0·16 (0·13 to 0·18) for 937 patients in the 14-day primaquine group, a difference of 0·02 (−0·02 to 0·05, p=0·3405). The incidence rate for 464 patients in the placebo group was 0·96 (95% CI 0·83 to 1·08) recurrences per person-year. Potentially drug-related serious adverse events within 42 days of starting treatment were reported in nine (1·0%) of 935 patients in the 7-day group, one (0·1%) of 937 in the 14-day group and none of 464 in the control arm. Four of the serious adverse events were significant haemolysis (three in the 7-day group and one in the 14-day group).
In patients with normal G6PD, 7-day primaquine was well tolerated and non-inferior to 14-day primaquine. The short-course regimen might improve adherence and therefore the effectiveness of primaquine for radical cure of P vivax malaria.
UK Department for International Development, UK Medical Research Council, UK National Institute for Health Research, and the Wellcome Trust through the Joint Global Health Trials Scheme (MR/K007424/1) and the Bill & Melinda Gates Foundation (OPP1054404).
New Guineans represent one of the oldest locally continuous populations outside Africa, harboring among the greatest linguistic and genetic diversity on the planet. Archeological and genetic evidence ...suggest that their ancestors reached Sahul (present day New Guinea and Australia) by at least 55,000 years ago (kya). However, little is known about this early settlement phase or subsequent dispersal and population structuring over the subsequent period of time. Here we report 379 complete Papuan mitochondrial genomes from across Papua New Guinea, which allow us to reconstruct the phylogenetic and phylogeographic history of northern Sahul. Our results support the arrival of two groups of settlers in Sahul within the same broad time window (50-65 kya), each carrying a different set of maternal lineages and settling Northern and Southern Sahul separately. Strong geographic structure in northern Sahul remains visible today, indicating limited dispersal over time despite major climatic, cultural, and historical changes. However, following a period of isolation lasting nearly 20 ky after initial settlement, environmental changes postdating the Last Glacial Maximum stimulated diversification of mtDNA lineages and greater interactions within and beyond Northern Sahul, to Southern Sahul, Wallacea and beyond. Later, in the Holocene, populations from New Guinea, in contrast to those of Australia, participated in early interactions with incoming Asian populations from Island Southeast Asia and continuing into Oceania.
Indonesia, an island nation as large as continental Europe, hosts a sizeable proportion of global human diversity, yet remains surprisingly undercharacterized genetically. Here, we substantially ...expand on existing studies by reporting genome-scale data for nearly 500 individuals from 25 populations in Island Southeast Asia, New Guinea, and Oceania, notably including previously unsampled islands across the Indonesian archipelago. We use high-resolution analyses of haplotype diversity to reveal fine detail of regional admixture patterns, with a particular focus on the Holocene. We find that recent population history within Indonesia is complex, and that populations from the Philippines made important genetic contributions in the early phases of the Austronesian expansion. Different, but interrelated processes, acted in the east and west. The Austronesian migration took several centuries to spread across the eastern part of the archipelago, where genetic admixture postdates the archeological signal. As with the Neolithic expansion further east in Oceania and in Europe, genetic mixing with local inhabitants in eastern Indonesia lagged behind the arrival of farming populations. In contrast, western Indonesia has a more complicated admixture history shaped by interactions with mainland Asian and Austronesian newcomers, which for some populations occurred more than once. Another layer of complexity in the west was introduced by genetic contact with South Asia and strong demographic events in isolated local groups.
Borneo was a crossroad of ancient dispersals, with some of the earliest Southeast Asian human remains and rock art. The island is home to traditionally hunter-gatherer Punan communities, whose ...origins, whether of subsistence reversion or long-term foraging, are unclear. The connection between its past and present-day agriculturalist inhabitants, who currently speak Austronesian languages and have composite and complex genetic ancestry, is equally opaque. Here, we analyze the genetic ancestry of the northeastern Bornean Punan Batu (who still practice some mobile hunting and gathering), Tubu, and Aput. We find deep ancestry connections, with a shared Asian signal outgrouping modern and ancient Austronesian-ancestry proxies, suggesting a time depth of more than 7,500 years. They also largely lack the mainland Southeast Asian signals of agricultural Borneans, who are themselves genetically heterogeneous. Our results support long-term inhabitation of Borneo by some Punan ancestors and reveal unexpected complexity in the origins and dispersal of Austronesian-expansion-related ancestry.
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•Northeast Bornean Punan communities show strong genetic ancestry connections•These communities outgroup modern and ancient Austronesian genetic proxies•Results support long-term occupation of Borneo by Punan-related people•Results are also inconsistent with recent subsistence reversion among Punan peoples
Anthropologists have long debated the origins of the traditional Punan hunter-gatherers of Borneo. Kusuma et al. show unique genetic ancestry shared between communities, supporting their long-term habitation on the island and rejecting the idea that they are agriculturalists who underwent recent subsistence reversion.
Indonesia is the world's fourth most populous country, host to striking levels of human diversity, regional patterns of admixture, and varying degrees of introgression from both Neanderthals and ...Denisovans. However, it has been largely excluded from the human genomics sequencing boom of the last decade. To serve as a benchmark dataset of molecular phenotypes across the region, we generated genome-wide CpG methylation and gene expression measurements in over 100 individuals from three locations that capture the major genomic and geographical axes of diversity across the Indonesian archipelago. Investigating between- and within-island differences, we find up to 10.55% of tested genes are differentially expressed between the islands of Sumba and New Guinea. Variation in gene expression is closely associated with DNA methylation, with expression levels of 9.80% of genes correlating with nearby promoter CpG methylation, and many of these genes being differentially expressed between islands. Genes identified in our differential expression and methylation analyses are enriched in pathways involved in immunity, highlighting Indonesia's tropical role as a source of infectious disease diversity and the strong selective pressures these diseases have exerted on humans. Finally, we identify robust within-island variation in DNA methylation and gene expression, likely driven by fine-scale environmental differences across sampling sites. Together, these results strongly suggest complex relationships between DNA methylation, transcription, archaic hominin introgression and immunity, all jointly shaped by the environment. This has implications for the application of genomic medicine, both in critically understudied Indonesia and globally, and will allow a better understanding of the interacting roles of genomic and environmental factors shaping molecular and complex phenotypes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Traces of interbreeding of Neanderthals and Denisovans with modern humans in the form of archaic DNA have been detected in the genomes of present-day human populations outside sub-Saharan Africa. Up ...to now, only nuclear archaic DNA has been detected in modern humans; we therefore attempted to identify archaic mitochondrial DNA (mtDNA) residing in modern human nuclear genomes as nuclear inserts of mitochondrial DNA (NUMTs).
We analysed 221 high-coverage genomes from Oceania and Indonesia using an approach which identifies reads that map both to the nuclear and mitochondrial DNA. We then classified reads according to the source of the mtDNA, and found one NUMT of Denisovan mtDNA origin, present in 15 analysed genomes; analysis of the flanking region suggests that this insertion is more likely to have happened in a Denisovan individual and introgressed into modern humans with the Denisovan nuclear DNA, rather than in a descendant of a Denisovan female and a modern human male.
Here we present our pipeline for detecting introgressed NUMTs in next generation sequencing data that can be used on genomes sequenced in the future. Further discovery of such archaic NUMTs in modern humans can be used to detect interbreeding between archaic and modern humans and can reveal new insights into the nature of such interbreeding events.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The settlement of Sahul, the lost continent of Oceania, remains one of the most ancient and debated human migrations. Modern New Guineans inherited a unique genetic diversity tracing back ...50,000 years, and yet there is currently no model reconstructing their past population dynamics. We generated 58 new whole-genome sequences from Papua New Guinea, filling geographical gaps in previous sampling, specifically to address alternative scenarios of the initial migration to Sahul and the settlement of New Guinea. Here, we present the first genomic models for the settlement of northeast Sahul considering one or two migrations from Wallacea. Both models fit our data set, reinforcing the idea that ancestral groups to New Guinean and Indigenous Australians split early, potentially during their migration in Wallacea where the northern route could have been favored. The earliest period of human presence in Sahul was an era of interactions and gene flow between related but already differentiated groups, from whom all modern New Guineans, Bismarck islanders, and Indigenous Australians descend. The settlement of New Guinea was probably initiated from its southeast region, where the oldest archaeological sites have been found. This was followed by two migrations into the south and north lowlands that ultimately reached the west and east highlands. We also identify ancient gene flows between populations in New Guinea, Australia, East Indonesia, and the Bismarck Archipelago, emphasizing the fact that the anthropological landscape during the early period of Sahul settlement was highly dynamic rather than the traditional view of extensive isolation.
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