Anna L. Gosling

The Genetic Diversity of the Nguni Breed of African Cattle (Bos spp.): Complete Mitochondrial Genomes of Haplogroup T1

Domesticated cattle were commonplace in northern Africa by about 7,000 years ago. Archaeological evidence, however, suggests they were not established in southern Africa until much later, no earlier than 2,000 years ago. Genetic reconstructions have started to shed light on the movement of African cattle, but efforts have been frustrated by a lack of data south of Ethiopia and the nature of the mitochondrial haplogroup T1 which is almost fixed across the continent. We sequenced 35 complete mitochondrial genomes from a South African herd of Nguni cattle, a breed historically associated with Bantu speaking farmers who were among the first to bring cattle to southern Africa. As expected, all individuals in the study were found to be members of haplogroup T1. Only half of the sub-haplogroups of T1 (T1a-T1f) are represented in our sample and the overwhelming majority (94%) in this study belong to subhaplogroup T1b. A previous study of African cattle found frequencies of T1b of 27% in Egypt and 69% in Ethiopia. These results are consistent with serial multiple founder effects significantly shaping the gene pool as cattle were moved from north to south across the continent. Interestingly, these mitochondrial data give no indication that the impacts of the founder effects were ameliorated by gene flow from recently introduced Indian cattle breeds.

Hyperuricaemia in the Pacific: why the elevated serum urate levels?

Pacific Island populations, particularly those of Polynesian descent, have a high prevalence of hyperuricaemia and gout. This is due to an inherently higher urate level among these populations with a demonstrated genetic predisposition. While an excess of urate can cause pathology, urate is also important for human health. It has been implicated as an antioxidant, has a neuroprotective role and is involved in innate immune responses. This paper provides a brief review of urate levels worldwide, with a particular focus on island Southeast Asia and the Pacific. We then present possible evolutionary explanations for the elevated serum urate levels among Pacific populations in the context of the physiological importance of urate and of the settlement history of the region. Finally, we propose that ancestry may play a significant role in hyperuricaemia in these populations and that exposure to malaria prior to population expansion into the wider Pacific may have driven genetic selection for variants contributing to high serum urate.

A European Mitochondrial Haplotype Identified in Ancient Phoenician Remains from Carthage, North Africa.

While Phoenician culture and trade networks had a significant impact on Western civilizations, we know little about the Phoenicians themselves. In 1994, a Punic burial crypt was discovered on Byrsa Hill, near the entry to the National Museum of Carthage in Tunisia. Inside this crypt were the remains of a young man along with a range of burial goods, all dating to the late 6th century BCE. Here we describe the complete mitochondrial genome recovered from the Young Man of Byrsa and identify that he carried a rare European haplogroup, likely linking his maternal ancestry to Phoenician influenced locations somewhere on the North Mediterranean coast, the islands of the Mediterranean or the Iberian Peninsula. This result not only provides the first direct ancient DNA evidence of a Phoenician individual but the earliest evidence of a European mitochondrial haplogroup, U5b2c1, in North Africa.

Pacific Populations, Metabolic Disease and ‘Just-So Stories’: A Critique of the ‘Thrifty Genotype’ Hypothesis in Oceania

Pacific populations have long been observed to suffer a high burden of metabolic disease, including obesity, type 2 diabetes and gout. The ‘Thrifty Genotype’ hypothesis has frequently been used to explain this high prevalence of disease. Here, the ‘Thrifty Genotype’ hypothesis and the evolutionary background of Pacific populations are examined. We question its relevance not only in the Pacific region but more generally. Not only has the hypothesis not been explicitly tested, but most archaeological and anthropological data from the Pacific fundamentally do not support its application.

Revisiting the Kalahari debate in the highlands: ancient DNA provides new faunal identifications at Sehonghong, Lesotho

ABSTRACT Large numbers of domestic stock have been reported among the faunal remains recovered from archaeological sites with predominantly forager-associated material culture in the highlands of Lesotho. These remains, in conjunction with the presence of artefacts of apparent agropastoralist origin, have led to the suggestion that either a process of neolithisation saw the adoption of livestock-keeping by traditionally foraging peoples, or that extensive contact and trade occurred between foraging groups in the mountains and distant agropastoralist communities. We present here ancient DNA evidence that the frequency of domestic stock in the faunal assemblages has been significantly overestimated and that, as a consequence, the nature of the relationships between highland foragers and agropastoralists has been misconstrued.

Mitochondrial genetic variation and gout in Māori 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 Māori and Pacific (Polynesian) people in Aotearoa New Zealand associate with susceptibility to gout. Methods 437 whole mitochondrial genomes from Māori 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 Māori 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 (β=0.003, P=7.1×10–7; β=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-1β in gout.

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

Abstract 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.

OP0158 Mitochondrial Genetic Variation and Susceptibility To Gout in Polynesians

Background Mitochondria appear to play a central role in the induction of an NLRP3 inflammatory response, an immune response critical for the development of gouty pathology. Mitochondria are in part self-encoding, possessing a 16.5 kB circular genome which encodes 36 genes. Therefore mitochondrial genetic variation may contribute to susceptibility to gout. Objectives The objective of this study was to test whether mitochondrial genetic variation and copy number among New Zealand Polynesians may be contributing to susceptibility to gout. The Māori and Pacific (Polynesian) populations of New Zealand exhibit a high prevalence of gout (6 and 8%, respectively). Methods 439 whole mitochondrial genomes belonging to Māori and Pacific men from New Zealand (327 cases, 112 controls) were sequenced to explore whether mitochondrial DNA (mtDNA) variation may contribute risk to gout. mtDNA copy number variation was also investigated by looking at relative read depth using Next Generation Sequencing data produced from whole genome sequencing and resequencing of urate loci. Quantitative PCR was undertaken for replication in an extended sample set of 540 Polynesian male and female cases and 530 controls. Results Within Polynesia, there is relatively little mitochondrial genetic diversity, with around 96% of those sequenced in this study belonging to the B4a1a and derived sub-lineages. A lineage-specific heteroplasmy in hypervariable region I was found to associate with a greater than three-fold higher risk of gout among the mitochondrial sequenced sample set (e.g. heteroplasmy at position 16179: OR 3.28, P=0.009; heteroplasmy at position 16181: 3.86, P=9x10–5; heteroplasmy at position 16182: 3.43, P=0.005). Quantitative PCR of mtDNA from the 1070 Polynesian gout cases and controls showed that individuals with gout possess less mtDNA, on average than healthy controls. With each unit increase in ΔCt (which reflects a decrease in mtDNA content), there was a 33% increase in gout risk (OR 1.33, P=0.003). The effect was stronger when looking at those participants who possessed urate levels exceeding 0.40 mmol L–1 (n=422, OR 1.69, P=0.0005). References It is unclear whether the reduced mtDNA copy number in gout is a result of the gouty pathology directly (i.e. the reduced mtDNA copy number is caused by the inflammatory processes underlying gout) or whether the reduced mtDNA copy number contributes to the risk of gout. The latter possibility is supported by the increase in risk using hyperuricemic controls suggesting that reduced mtDNA copy number plays a role in inflammation. Given emerging research is showing that mitochondria play a central role in the induction of the NLRP3 inflammasome, in particular with the co-localisation of the NLRP3 and ASC sub-units, a process essential for the generation of IL-1β, these observations may be significant. Exploring mitochondrial genetic variation may further elucidate the inflammatory processes underlying gout. Acknowledgement The New Zealand Health Research Council, Lottery Health New Zealand, Arthritis New Zealand and the National Institute of Health (United States) are thanked for funding this study. Disclosure of Interest T. Merriman Grant/research support from: ArdeaBio, A. Gosling: None declared, J. Boocock: None declared, N. Dalbeth Grant/research support from: AstraZeneca, Fonterra, ArdeaBio, Consultant for: Menarini, Takeda, Teijin, Pfizer, Crealta, Cymabay, L. Stamp: None declared, E. Stahl: None declared, H. Choi: None declared, L. Matisoo-Smith: None declared

Ancient mitogenomes of Phoenicians from Sardinia and Lebanon: A story of settlement, integration, and female mobility

The Phoenicians emerged in the Northern Levant around 1800 BCE and by the 9th century BCE had spread their culture across the Mediterranean Basin, establishing trading posts, and settlements in various European Mediterranean and North African locations. Despite their widespread influence, what is known of the Phoenicians comes from what was written about them by the Greeks and Egyptians. In this study, we investigate the extent of Phoenician integration with the Sardinian communities they settled. We present 14 new ancient mitogenome sequences from pre-Phoenician (~1800 BCE) and Phoenician (~700–400 BCE) samples from Lebanon (n = 4) and Sardinia (n = 10) and compare these with 87 new complete mitogenomes from modern Lebanese and 21 recently published pre-Phoenician ancient mitogenomes from Sardinia to investigate the population dynamics of the Phoenician (Punic) site of Monte Sirai, in southern Sardinia. Our results indicate evidence of continuity of some lineages from pre-Phoenician populations suggesting integration of indigenous Sardinians in the Monte Sirai Phoenician community. We also find evidence of the arrival of new, unique mitochondrial lineages, indicating the movement of women from sites in the Near East or North Africa to Sardinia, but also possibly from non-Mediterranean populations and the likely movement of women from Europe to Phoenician sites in Lebanon. Combined, this evidence suggests female mobility and genetic diversity in Phoenician communities, reflecting the inclusive and multicultural nature of Phoenician society.

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.