We report a method called ContamLD for estimating autosomal ancient DNA (aDNA) contamination by measuring the breakdown of linkage disequilibrium in a sequenced individual due to the introduction of ...contaminant DNA. ContamLD leverages the idea that contaminants should have haplotypes uncorrelated to those of the studied individual. Using simulated data, we confirm that ContamLD accurately infers contamination rates with low standard errors: for example, less than 1.5% standard error in cases with less than 10% contamination and 500,000 sequences covering SNPs. This method is optimized for application to aDNA, taking advantage of characteristic aDNA damage patterns to provide calibrated contamination estimates, and is available at https://github.com/nathan-nakatsuka/ContamLD .
Humans settled the Caribbean about 6,000 years ago, and ceramic use and intensified agriculture mark a shift from the Archaic to the Ceramic Age at around 2,500 years ago
. Here we report genome-wide ...data from 174 ancient individuals from The Bahamas, Haiti and the Dominican Republic (collectively, Hispaniola), Puerto Rico, Curaçao and Venezuela, which we co-analysed with 89 previously published ancient individuals. Stone-tool-using Caribbean people, who first entered the Caribbean during the Archaic Age, derive from a deeply divergent population that is closest to Central and northern South American individuals; contrary to previous work
, we find no support for ancestry contributed by a population related to North American individuals. Archaic-related lineages were >98% replaced by a genetically homogeneous ceramic-using population related to speakers of languages in the Arawak family from northeast South America; these people moved through the Lesser Antilles and into the Greater Antilles at least 1,700 years ago, introducing ancestry that is still present. Ancient Caribbean people avoided close kin unions despite limited mate pools that reflect small effective population sizes, which we estimate to be a minimum of 500-1,500 and a maximum of 1,530-8,150 individuals on the combined islands of Puerto Rico and Hispaniola in the dozens of generations before the individuals who we analysed lived. Census sizes are unlikely to be more than tenfold larger than effective population sizes, so previous pan-Caribbean estimates of hundreds of thousands of people are too large
. Confirming a small and interconnected Ceramic Age population
, we detect 19 pairs of cross-island cousins, close relatives buried around 75 km apart in Hispaniola and low genetic differentiation across islands. Genetic continuity across transitions in pottery styles reveals that cultural changes during the Ceramic Age were not driven by migration of genetically differentiated groups from the mainland, but instead reflected interactions within an interconnected Caribbean world
.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
More than two hundred papers have reported genome-wide data from ancient humans. While the raw data for the vast majority are fully publicly available testifying to the commitment of the ...paleogenomics community to open data, formats for both raw data and meta-data differ. There is thus a need for uniform curation and a centralized, version-controlled compendium that researchers can download, analyze, and reference. Since 2019, we have been maintaining the Allen Ancient DNA Resource (AADR), which aims to provide an up-to-date, curated version of the world's published ancient human DNA data, represented at more than a million single nucleotide polymorphisms (SNPs) at which almost all ancient individuals have been assayed. The AADR has gone through six public releases at the time of writing and review of this manuscript, and crossed the threshold of >10,000 individuals with published genome-wide ancient DNA data at the end of 2022. This note is intended as a citable descriptor of the AADR.
Ancient DNA sampling methods-although optimized for efficient DNA extraction-are destructive, relying on drilling or cutting and powdering (parts of) bones and teeth. As the field of ancient DNA has ...grown, so have concerns about the impact of destructive sampling of the skeletal remains from which ancient DNA is obtained. Due to a particularly high concentration of endogenous DNA, the cementum of tooth roots is often targeted for ancient DNA sampling, but destructive sampling methods of the cementum often result in the loss of at least one entire root. Here, we present a minimally destructive method for extracting ancient DNA from dental cementum present on the surface of tooth roots. This method does not require destructive drilling or grinding, and, following extraction, the tooth remains safe to handle and suitable for most morphological studies, as well as other biochemical studies, such as radiocarbon dating. We extracted and sequenced ancient DNA from 30 teeth (and nine corresponding petrous bones) using this minimally destructive extraction method in addition to a typical tooth sampling method. We find that the minimally destructive method can provide ancient DNA that is of comparable quality to extracts produced from teeth that have undergone destructive sampling processes. Further, we find that a rigorous cleaning of the tooth surface combining diluted bleach and UV light irradiation seems sufficient to minimize external contaminants usually removed through the physical removal of a superficial layer when sampling through regular powdering methods.
Proprotein convertase subtilisin kexin-like 9 (PCSK9) promotes the degradation of low density lipoprotein receptor (LDLR) and plays an important role in regulating plasma LDL-cholesterol levels. We ...have shown that the epidermal growth factor precursor homology domain A (EGF-A) of the LDLR is critical for PCSK9 binding at the cell surface (pH 7.4). Here, we further characterized the role of EGF-A in binding of PCSK9 to the LDLR. We found that PCSK9 efficiently bound to the LDLR but not to other LDLR family members. Replacement of EGF-A in the very low density lipoprotein receptor (VLDLR) with EGF-A of the LDLR promoted the degradation of the mutant VLDLR induced by PCSK9. Furthermore, we found that PCSK9 bound to recombinant EGF-A in a pH-dependent manner with stronger binding at pH 6.0. We also identified amino acid residues in EGF-A of the LDLR important for PCSK9 binding. Mutations G293H, D299V, L318D, and L318H reduced PCSK9 binding to the LDLR at neutral pH without effect at pH 6.0, while mutations R329P and E332G reduced PCSK9 binding at both pH values. Thus, our findings reveal that EGF-A of the LDLR is critical for PCSK9 binding at the cell surface (neutral pH) and at the acidic endosomal environment (pH 6.0), but different determinants contribute to efficient PCSK9 binding in different pH environments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract The purpose of this study is to investigate unique features of body segments in fall and activities of daily living (ADL) to make automatic detection of fall in its descending phase before ...the impact. Thus, fall-related injuries can be prevented or reduced by deploying feedback systems before the impact. In this study, the authors propose the following hypothesis: (1) thigh segment normally does not go beyond certain threshold angle to forward and sideways directions in ADL and (2) even if it does, the angular characteristics measured at torso and thigh differ from one another in ADL whereas in the case of fall, they become congruent. These two factors can be used to distinguish fall from ADL in its inception. Vicon 3-D motion analysis system was used in this study. High level of correlation between thigh and torso segments (corr > 0.99) was found for fall activities and low correlation coefficients (mean corr for lateral movements is 0.2338 and for sagittal movements is −0.665) were observed in ADL. By applying the hypothesis, all simulated falls could be detected with no false alarms and around 700 ms lead-time before the impact was achieved in pre-impact fall detection. It is the longest lead-time obtained so far in pre-impact fall detection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Relatively little is known about Nubia's genetic landscape prior to the influence of the Islamic migrations that began in the late 1st millennium CE. Here, we increase the number of ancient ...individuals with genome-level data from the Nile Valley from three to 69, reporting data for 66 individuals from two cemeteries at the Christian Period (~650-1000 CE) site of Kulubnarti, where multiple lines of evidence suggest social stratification. The Kulubnarti Nubians had ~43% Nilotic-related ancestry (individual variation between ~36-54%) with the remaining ancestry consistent with being introduced through Egypt and ultimately deriving from an ancestry pool like that found in the Bronze and Iron Age Levant. The Kulubnarti gene pool - shaped over a millennium - harbors disproportionately female-associated West Eurasian-related ancestry. Genetic similarity among individuals from the two cemeteries supports a hypothesis of social division without genetic distinction. Seven pairs of inter-cemetery relatives suggest fluidity between cemetery groups. Present-day Nubians are not directly descended from the Kulubnarti Nubians, attesting to additional genetic input since the Christian Period.
The strategy of in-solution enrichment for hundreds of thousands of single-nucleotide polymorphisms (SNPs) has been used to analyze >70% of individuals with genome-scale ancient DNA published to ...date. This approach makes it economical to study ancient samples with low proportions of human DNA and increases the rate of conversion of sampled remains into interpretable data. So far, nearly all such data have been generated using a set of bait sequences targeting about 1.24 million SNPs (the "1240k reagent"), but synthesis of the reagent has been cost-effective for only a few laboratories. In 2021, two companies, Daicel Arbor Biosciences and Twist Bioscience, made available assays that target the same core set of SNPs along with supplementary content. We test all three assays on a common set of 27 ancient DNA libraries and show that all three are effective at enriching many hundreds of thousands of SNPs. For all assays, one round of enrichment produces data that are as useful as two. In our testing, the "Twist Ancient DNA" assay produces the highest coverages, greatest uniformity on targeted positions, and almost no bias toward enriching one allele more than another relative to shotgun sequencing. We also identify hundreds of thousands of targeted SNPs for which there is minimal allelic bias when comparing 1240k data to either shotgun or Twist data. This facilitates coanalysis of the large data sets that have been generated using 1240k and Twist capture, as well as shotgun sequencing approaches.
We report an ancient genome from the Indus Valley Civilization (IVC). The individual we sequenced fits as a mixture of people related to ancient Iranians (the largest component) and Southeast Asian ...hunter-gatherers, a unique profile that matches ancient DNA from 11 genetic outliers from sites in Iran and Turkmenistan in cultural communication with the IVC. These individuals had little if any Steppe pastoralist-derived ancestry, showing that it was not ubiquitous in northwest South Asia during the IVC as it is today. The Iranian-related ancestry in the IVC derives from a lineage leading to early Iranian farmers, herders, and hunter-gatherers before their ancestors separated, contradicting the hypothesis that the shared ancestry between early Iranians and South Asians reflects a large-scale spread of western Iranian farmers east. Instead, sampled ancient genomes from the Iranian plateau and IVC descend from different groups of hunter-gatherers who began farming without being connected by substantial movement of people.
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•The individual was from a population that is the largest source of ancestry for South Asians•Iranian-related ancestry in South Asia split from Iranian plateau lineages >12,000 years ago•First farmers of the Fertile Crescent contributed little to no ancestry to later South Asians
A genome from the Indus Valley Civilization is from a population that is the largest source for South Asians. The population has no detectable ancestry from Steppe pastoralists or from Anatolian and Iranian farmers, suggesting farming in South Asia arose from local foragers rather than from large-scale migration from the West.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
How food production first entered eastern Africa ~5000 years ago and the extent to which people moved with livestock is unclear. We present genome-wide data from 41 individuals associated with Later ...Stone Age, Pastoral Neolithic (PN), and Iron Age contexts in what are now Kenya and Tanzania to examine the genetic impacts of the spreads of herding and farming. Our results support a multiphase model in which admixture between northeastern African-related peoples and eastern African foragers formed multiple pastoralist groups, including a genetically homogeneous PN cluster. Additional admixture with northeastern and western African-related groups occurred by the Iron Age. These findings support several movements of food producers while rejecting models of minimal admixture with foragers and of genetic differentiation between makers of distinct PN artifacts.
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