Building capacity to conduct genetic epidemiology research on hyperuricaemia and gout in an Indigenous community in Guam.

Background: Gout, the most common inflammatory arthritis disease, and hyperuricaemia onset are influenced by environmental and genetic factors. We sought to investigate these factors in an Indigenous community in Guam. Methods: In this cross-sectional study, the University of Guam led the qualitative inquiry with the native community, training (pre-screening of participants, data collection methods, and biospecimen handling), study implementation (outreach and recruitment, data collection, and DNA extraction and quantification), and qualitative and epidemiologic data analyses. Recruitment targets were based on demographic representation in current census data. The University of Otago collaborated on ethics guidance, working with Indigenous communities, and led the genetic sequencing and genetic data analysis. Participants were recruited in Guam from Fall 2019 to Spring 2022. Results: Of the 359 participants, most self-identified as Native CHamorus (61.6%) followed by Other Micronesians (22.0%), and Filipinos (15.6%). The prevalence of metabolic conditions from highest to lowest were obesity (55.6%), hyperuricaemia (36.0%), hypertension (27.8%), gout (23.0%), diabetes (14.9%), cardiovascular disease (8.4%), kidney disease (7.3%), and liver disease (3.4%). Compared to Filipinos and Other Micronesians, significantly more CHamorus had hyperuricaemia (42.1% versus 26.8% in Filipinos and 25.3% in Other Micronesians), gout (28.5% versus 21.4% and 8.9%), diabetes (19.5% versus 8.9% and 6.3%), and hypertension (33.9% versus 19.6% and 16.5%). Conclusions: We estimated the prevalence of metabolic conditions, especially gout and hyperuricaemia, and found statistical differences among major ethnic groups in Guam, all while obtaining the Indigenous community's feedback on the genetic study and building gout research capacity. The results of ongoing genetic sequencing will be used to understand molecular causes of gout in Guam.

Community partnerships are fundamental to ethical ancient DNA research.

The ethics of the scientific study of Ancestors has long been debated by archaeologists, bioanthropologists, and, more recently, ancient DNA (aDNA) researchers. This article responds to the article "Ethics of DNA research on human remains: five globally applicable guidelines" published in 2021 in Nature by a large group of aDNA researchers and collaborators. We argue that these guidelines do not sufficiently consider the interests of community stakeholders, including descendant communities and communities with potential, but yet unestablished, ties to Ancestors. We focus on three main areas of concern with the guidelines. First is the false separation of "scientific" and "community" concerns and the consistent privileging of researcher perspectives over those of community members. Second, the commitment of the guidelines' authors to open data ignores the principles and practice of Indigenous Data Sovereignty. Further, the authors argue that involving community members in decisions about publication and data sharing is unethical. We argue that excluding community perspectives on "ethical" grounds is convenient for researchers, but it is not, in fact, ethical. Third, we stress the risks of not consulting communities that have established or potential ties to Ancestors, using two recent examples from the literature. Ancient DNA researchers cannot focus on the lowest common denominator of research practice, the bare minimum that is legally necessary. Instead, they should be leading multidisciplinary efforts to create processes to ensure communities from all regions of the globe are identified and engaged in research that affects them. This will often present challenges, but we see these challenges as part of the research, rather than a distraction from the scientific endeavor. If a research team does not have the capacity to meaningfully engage communities, questions must be asked about the value and benefit of their research.

Ancient and modern mitogenomes from Central Argentina: new insights into population continuity, temporal depth and migration in South America.

The inverted triangle shape of South America places Argentina territory as a geographical crossroads between the two principal peopling streams that followed either the Pacific or the Atlantic coasts, which could have then merged in Central Argentina (CA). Although the genetic diversity from this region is therefore crucial to decipher past population movements in South America, its characterization has been overlooked so far. We report 92 modern and 22 ancient mitogenomes spanning a temporal range of 5000 years, which were compared with a large set of previously reported data. Leveraging this dataset representative of the mitochondrial diversity of the subcontinent, we investigate the maternal history of CA populations within a wider geographical context. We describe a large number of novel clades within the mitochondrial DNA tree, thus providing new phylogenetic interpretations for South America. We also identify several local clades of great temporal depth with continuity until the present time, which stem directly from the founder haplotypes, suggesting that they originated in the region and expanded from there. Moreover, the presence of lineages characteristic of other South American regions reveals the existence of gene flow to CA. Finally, we report some lineages with discontinuous distribution across the Americas, which suggest the persistence of relic lineages likely linked to the first population arrivals. The present study represents to date the most exhaustive attempt to elaborate a Native American genetic map from modern and ancient complete mitochondrial genomes in Argentina and provides relevant information about the general process of settlement in South America.

First mitochondrial genome of the Caucasian squirrel Sciurus anomalus (Rodentia, Sciuridae).

The Caucasian Squirrel, Sciurus anomalus, is the only representative of the Sciuridae family in the Eastern Mediterranean region. In this study, the mitochondrial genome of the Sciurus anomalus species was generated, and we investigate its phylogenetic position within the Sciuridae family. The generated mitogenome sequence is 16,234 bp. It is composed of a control region and a conserved set of 37 genes containing 13 protein-coding genes, 22 tRNA genes and 2 rRNA genes.

First mitochondrial genome of the marbled polecat Vormela peregusna (Carnivora, Mustelidae).

The marbled polecat, Vormela peregusna, is one of the least studied species in the Mustelidae family, especially with regard to phylogeography and genetic diversity. In this study, we determined the mitochondrial genome sequence of V. peregusna and investigated its position within the Mustelidae phylogeny. The generated mitogenome is 15,982 bp in length; it consists of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and a control region.

Autosomal genetics and Y-chromosome haplogroup L1b-M317 reveal Mount Lebanon Maronites as a persistently non-emigrating population.

Currently, there are 18 different religious communities living in Lebanon. While evolving primarily within Lebanon, these communities show a level of local isolation as demonstrated previously from their Y-haplogroup distributions. In order to trace the origins and migratory patterns that may have led to the genetic isolation and autosomal clustering in some of these communities we analyzed Y-chromosome STR and SNP sample data from 6327 individuals, in addition to whole genome autosomal sample data from 609 individuals, from Mount Lebanon and other surrounding communities. We observed Y chromosome L1b Levantine STR branching that occurred around 5000 years ago. Autosomal DNA analyses suggest that the North Lebanese Mountain Maronite community possesses an ancestral Fertile Crescent genetic component distinct from other populations in the region. We suggest that the Levantine L1b group split from the Caucasus ancestral group around 7300 years ago and migrated to the Levant. This event was distinct from the earlier expansions from the Caucasus region that contributed to the wider Levantine populations. Differential cultural adaption by populations from the North Lebanese Mountains are clearly aligned with the L1b haplotype STR haplogroup clusters, indicating pre-existing and persistent cultural barriers marked by the transmission of L1b lineages. Our findings highlight the value of uniparental haplogroups and STR haplotype data for elucidating biosocial events among these populations.

A multi-isotope, multi-tissue study of colonial origins and diet in New Zealand.

OBJECTIVES: Colonial period New Zealand was lauded as a land of plenty, where colonists could improve their station in life and secure a future for their families. Our understanding of colonial experience, however, is often shaped by historical records which communicate a state-sponsored version of history. This study aims to reconstruct the lives of settlers using isotopic evidence from the colonial skeletons themselves. MATERIALS AND METHODS: We use skeletal remains from recently excavated colonial sites in Otago (South Island, New Zealand) to illustrate the information that can be gleaned from the isotopic analysis of individuals. We use 87 Sr/86 Sr to identify European settlers, and δ13 C and δ15 N from collagen and hair keratin, as well as dental enamel carbonate δ13 C to trace dietary change over their life-courses. RESULTS: Strontium isotope analysis shows that all adults in our sample are non-local. Dietary isotopes show that while most individuals had relatively consistent childhood diet, one individual with more rural origins likely had seasonal use of resources during childhood. While some members of the population seem to have increased their meat intake in the new colony most do not have clear evidence for this. DISCUSSION: We show the diversity of human experience in first-generation New Zealanders both prior to emigration and in the new colony. Despite colonial propaganda claiming that circumstances in New Zealand were improved for all settlers, we have little evidence for this, aside from among individuals of potentially high status.

A tale of textiles: Genetic characterization of historical paper mulberry barkcloth from Oceania.

Humans introduced paper mulberry (Broussonetia papyrifera) from Taiwan into the Pacific over 5000 years ago as a fiber source to make barkcloth textiles that were, and still are, important cultural artifacts throughout the Pacific. We have used B. papyrifera, a species closely associated to humans, as a proxy to understand the human settlement of the Pacific Islands. We report the first genetic analysis of paper mulberry textiles from historical and archaeological contexts (200 to 50 years before present) and compare our results with genetic data obtained from contemporary and herbarium paper mulberry samples. Following stringent ancient DNA protocols, we extracted DNA from 13 barkcloth textiles. We confirmed that the fiber source is paper mulberry in nine of the 13 textiles studied using the nuclear ITS-1 marker and by statistical estimates. We detected high genetic diversity in historical Pacific paper mulberry barkcloth with a set of ten microsatellites, showing new alleles and specific genetic patterns. These genetic signatures allow tracing connections to plants from the Asian homeland, Near and Remote Oceania, establishing links not observed previously (using the same genetic tools) in extant plants or herbaria samples. These results show that historic barkcloth textiles are cultural materials amenable to genetic analysis to reveal human history and that these artifacts may harbor evidence of greater genetic diversity in Pacific B. papyrifera in the past.

Exploitation and utilization of tropical rainforests indicated in dental calculus of ancient Oceanic Lapita culture colonists.

Remote Oceania, which largely consists of islands covered in tropical forests, was the last region on earth to be successfully colonized by humans, beginning 3,000 years ago. We examined human dental calculus from burials in an ancient Lapita culture cemetery to gain insight into the early settlement of this previously untouched tropical environment, specifically on the island of Efate in Vanuatu. Dental calculus is an ideal material to analyse questions of human and plant interactions due to the ingestion of plant-derived microparticles that become incorporated into the calculus as it forms throughout a person's life. Most of the microparticles identified here are from tree and shrub resources, including a ~2,900 calibrated (cal) BP example of banana in Remote Oceania, providing direct evidence for the importance of forests and arboriculture during the settlement of Remote Oceania.

Human mediated translocation of Pacific paper mulberry [Broussonetia papyrifera (L.) L'Hér. ex Vent. (Moraceae)]: Genetic evidence of dispersal routes in Remote Oceania.

Paper mulberry, Broussonetia papyrifera (L.) L'Hér. ex Vent. (Moraceae), a dioecious species, was transported by humans from Taiwan to the islands of Remote Oceania. Its introduction and cultivation in Remote Oceania was intentional due to its cultural importance as a fiber source for barkcloth textiles. The aim of this study was to explore the genetic diversity and structure of paper mulberry populations within Remote Oceania in order to infer dispersal patterns that may reflect past human interaction among island groups. We present the integrated analysis of 380 samples (313 contemporary and 67 herbarium specimens) collected in Near and Remote Oceania. Genetic characterization was based on a set of ten microsatellites developed for B. papyrifera and complemented with the analysis of the ribosomal internal transcribed spacer ITS-1 sequence, a sex marker and the chloroplast ndhF-rpl32 intergenic spacer. Microsatellite data identify a total of 64 genotypes, despite this being a clonally propagated crop, and show three major dispersal hubs within Remote Oceania, centered on the islands of Fiji, Tonga, and Pitcairn. Of 64 genotypes identified, 55 correspond to genotypes associated to female-sexed plants that probably descend from plants introduced by the prehistoric Austronesian-speaking voyagers. The ratio of accessions to genotypes between herbarium and contemporary samples, suggests recent loss of genetic diversity. In addition to the chloroplast haplotypes described previously, we detected two new haplotypes within Remote Oceania both originating in Taiwan. This is the first study of a commensal species to show genetic structuring within Remote Oceania. In spite of the genetic bottleneck, the presence of only one sex, a timespan of less than 5000 years, and asexual propagation of this crop in Remote Oceania, we detect genetic diversity and regional structuring. These observations suggest specific migration routes between island groups within Remote Oceania.

Correction: Investigating the Global Dispersal of Chickens in Prehistory Using Ancient Mitochondrial DNA Signatures.

[This corrects the article DOI: 10.1371/journal.pone.0039171.].

People from Ibiza: an unexpected isolate in the Western Mediterranean.

In this study, we seek to understand and to correlate the genetic patterns observed in the population of the island of Ibiza in the Western Mediterranean basin with past events. Genome-wide genotypes of 189 samples representing 13 of 17 regions in Spain have been analyzed, in addition to 105 samples from the Levant, 157 samples from North Africa, and one ancient sample from the Phoenician Cas Molí site in Ibiza. Before the Catalans conquered the island in 1235 CE, Ibiza (Eivissa) had already been influenced by several cultures, starting with the Phoenicians, then the Carthaginians, followed by the Umayyads. The impact of these various cultures on the genetic structure of the islanders is still unexplored. Our results show a clear distinction between Ibiza and the rest of Spain. To investigate whether this was due to the Phoenician colonization or to more recent events, we compared the genomes of current Ibizans to that of an ancient Phoenician sample from Ibiza and to both modern Levantine and North African genomes. We did not identify any trace of Phoenician ancestry in the current Ibizans. Interestingly, the analysis of runs of homozygosity and changes in the effective population size through time support the idea that drift has shaped the genetic structure of current Ibizans. In addition to the small carrying capacity of the island, Ibiza experienced a series of dramatic demographic changes due to several instances of famine, war, malaria and plague that could have significantly contributed to its current genetic differentiation.

Ancient DNA of Phoenician remains indicates discontinuity in the settlement history of Ibiza.

Ibiza was permanently settled around the 7th century BCE by founders arriving from west Phoenicia. The founding population grew significantly and reached its height during the 4th century BCE. We obtained nine complete mitochondrial genomes from skeletal remains from two Punic necropoli in Ibiza and a Bronze Age site from Formentara. We also obtained low coverage (0.47X average depth) of the genome of one individual, directly dated to 361-178 cal BCE, from the Cas Molí site on Ibiza. We analysed and compared ancient DNA results with 18 new mitochondrial genomes from modern Ibizans to determine the ancestry of the founders of Ibiza. The mitochondrial results indicate a predominantly recent European maternal ancestry for the current Ibizan population while the whole genome data suggest a significant Eastern Mediterranean component. Our mitochondrial results suggest a genetic discontinuity between the early Phoenician settlers and the island's modern inhabitants. Our data, while limited, suggest that the Eastern or North African influence in the Punic population of Ibiza was primarily male dominated.

Genomic medicine must reduce, not compound, health inequities: the case for hauora-enhancing genomic resources for New Zealand.

Precision medicine seeks to draw on data from both individuals and populations across disparate domains to influence and support diagnosis, management and prevention in healthcare at the level of the individual patient and their family/whanau. Central to this initiative is incorporating the effects of the inherent variation that lies within genomes and can influence health outcomes. Identifying and interpreting such variation requires an accurate, valid and representative dataset to firstly define what variants are present and then assess the potential relevance for the health of a person, their family/whanau and the wider community to which they belong. Globally the variation embedded within genomes differs enormously and has been shaped by the size, constitution, historical origins and evolutionary history of their source populations. Maori, and more broadly Pacific peoples, differ substantially in terms of genomic variation compared to the more closely studied European and Asian populations. In the absence of accurate genomic information from Maori and Pacific populations, the precise interpretation of genomic data and the success and benefits of genomic medicine will be disproportionately less for those Maori and Pacific peoples. In this viewpoint article we, as a group of healthcare professionals, researchers and scientists, present a case for assembling genomic resources that catalogue the characteristics of the genomes of New Zealanders, with an emphasis on peoples of Maori and Polynesian ancestry, as a healthcare imperative. In proposing the creation of these resources, we note that their governance and management must be led by iwi and Maori and Pacific representatives. Assembling a genomic resource must be informed by cultural concepts and values most especially understanding that, at a physical and spiritual level, whakapapa is embodied within the DNA of a person. Therefore DNA and genomic data that connects to whakapapa (genealogy) is considered a taonga (something precious and significant), and its storage, utilisation and interpretation is a culturally significant activity. Furthermore, such resources are not proposed to primarily enable comparisons between those with Maori and broader Pacific ancestries and other Aotearoa peoples but to place an understanding of the genetic contributors to their health outcomes in a valid context. Ongoing oversight and governance of such taonga by Maori and Pacific representatives will maximise hauora (health) while also minimising the risk of misuse of this information.

The evolutionary history and human settlement of Australia and the Pacific.

Understanding the timing and processes involved in the human settlement of Australia and the Pacific has significance for addressing some key debates relating to human origins and population expansions worldwide. Despite this, for many years, Pacific populations were seriously under-represented in genetic studies of human origins. The last 15 years, however, have seen some major genetic studies involving Australian and Pacific populations which have shed light on their origins and interactions, and the last five years have seen some major developments that are challenging long-held concepts of Pacific settlement.

Walking backwards into the future: the need for a holistic evolutionary approach in Pacific health research.

CONTEXT: The Pacific region has had a complex human history. It has been subject to multiple major human dispersal and colonisation events, including some of the earliest Out-of-Africa migrations, the so-called Austronesian expansion of people out of Island Southeast Asia, and the more recent arrival of Europeans. Despite models of island isolation, evidence suggests significant levels of interconnectedness that vary in direction and frequency over time. The Pacific Ocean covers a vast area and its islands provide an array of different physical environments with variable pathogen loads and subsistence opportunities. These diverse environments likely caused Pacific peoples to adapt (both genetically and culturally) in unique ways. Differences in genetic background, in combination with adaptation, likely affect their susceptibility to non-communicable diseases. OBJECTIVES: Here we provide an overview of some of the key issues in the natural and human history of the Pacific region which are likely to impact human health. We argue that understanding the evolutionary and cultural history of Pacific peoples is essential for the generation of testable hypotheses surrounding potential causes of elevated disease susceptibility among Pacific peoples.

Mitochondrial genetic variation and gout in Maori and Pacific people living in Aotearoa New Zealand.

OBJECTIVE: Mitochondria have an important role in the induction of the NLRP3 inflammasome response central in gout. The objective was to test whether mitochondrial genetic variation and copy number in New Zealand Maori and Pacific (Polynesian) people in Aotearoa New Zealand associate with susceptibility to gout. METHODS: 437 whole mitochondrial genomes from Maori and Pacific people (predominantly men) from Aotearoa New Zealand (327 people with gout, 110 without gout) were sequenced. Mitochondrial DNA copy number variation was determined by assessing relative read depth using data produced from whole genome sequencing (32 cases, 43 controls) and targeted resequencing of urate loci (151 cases, 222 controls). Quantitative PCR was undertaken for replication of copy number findings in an extended sample set of 1159 Maori and Pacific men and women (612 cases, 547 controls). RESULTS: There was relatively little mitochondrial genetic diversity, with around 96% of those sequenced in this study belonging to the B4a1a and derived sublineages. A B haplogroup heteroplasmy in hypervariable region I was found to associate with a higher risk of gout among the mitochondrial sequenced sample set (position 16181: OR=1.57, P=0.001). Increased copies of mitochondrial DNA were found to protect against gout risk with the effect being consistent when using hyperuricaemic controls across each of the three independent sample sets (OR=0.89, P=0.007; OR=0.90, P=0.002; OR=0.76, P=0.03). Paradoxically, an increase of mitochondrial DNA also associated with an increase in gout flare frequency in people with gout in the two larger sample sets used for the copy number analysis (ß=0.003, P=7.1×10-7; ß=0.08, P=1.2×10-4). CONCLUSION: Association of reduced copy number with gout in hyperuricaemia was replicated over three Polynesian sample sets. Our data are consistent with emerging research showing that mitochondria are important for the colocalisation of the NLRP3 and ASC inflammasome subunits, a process essential for the generation of interleukin-1ß in gout.

Continuity and Admixture in the Last Five Millennia of Levantine History from Ancient Canaanite and Present-Day Lebanese Genome Sequences.

The Canaanites inhabited the Levant region during the Bronze Age and established a culture that became influential in the Near East and beyond. However, the Canaanites, unlike most other ancient Near Easterners of this period, left few surviving textual records and thus their origin and relationship to ancient and present-day populations remain unclear. In this study, we sequenced five whole genomes from ∼3,700-year-old individuals from the city of Sidon, a major Canaanite city-state on the Eastern Mediterranean coast. We also sequenced the genomes of 99 individuals from present-day Lebanon to catalog modern Levantine genetic diversity. We find that a Bronze Age Canaanite-related ancestry was widespread in the region, shared among urban populations inhabiting the coast (Sidon) and inland populations (Jordan) who likely lived in farming societies or were pastoral nomads. This Canaanite-related ancestry derived from mixture between local Neolithic populations and eastern migrants genetically related to Chalcolithic Iranians. We estimate, using linkage-disequilibrium decay patterns, that admixture occurred 6,600-3,550 years ago, coinciding with recorded massive population movements in Mesopotamia during the mid-Holocene. We show that present-day Lebanese derive most of their ancestry from a Canaanite-related population, which therefore implies substantial genetic continuity in the Levant since at least the Bronze Age. In addition, we find Eurasian ancestry in the Lebanese not present in Bronze Age or earlier Levantines. We estimate that this Eurasian ancestry arrived in the Levant around 3,750-2,170 years ago during a period of successive conquests by distant populations.

Mapping Post-Glacial expansions: The Peopling of Southwest Asia.

Archaeological, palaeontological and geological evidence shows that post-glacial warming released human populations from their various climate-bound refugia. Yet specific connections between these refugia and the timing and routes of post-glacial migrations that ultimately established modern patterns of genetic variation remain elusive. Here, we use Y-chromosome markers combined with autosomal data to reconstruct population expansions from regional refugia in Southwest Asia. Populations from three regions in particular possess distinctive autosomal genetic signatures indicative of likely refugia: one, in the north, centered around the eastern coast of the Black Sea, the second, with a more Levantine focus, and the third in the southern Arabian Peninsula. Modern populations from these three regions carry the widest diversity and may indeed represent the most likely descendants of the populations responsible for the Neolithic cultures of Southwest Asia. We reveal the distinct and datable expansion routes of populations from these three refugia throughout Southwest Asia and into Europe and North Africa and discuss the possible correlations of these migrations to various cultural and climatic events evident in the archaeological record of the past 15,000 years.