Geoff Chambers

Testing the thrifty gene hypothesis: the Gly482Ser variant in PPARGC1A is associated with BMI in Tongans

BackgroundThe thrifty gene hypothesis posits that, in populations that experienced periods of feast and famine, natural selection favoured individuals carrying thrifty alleles that promote the storage of fat and energy. Polynesians likely experienced long periods of cold stress and starvation during their settlement of the Pacific and today have high rates of obesity and type 2 diabetes (T2DM), possibly due to past positive selection for thrifty alleles. Alternatively, T2DM risk alleles may simply have drifted to high frequency in Polynesians. To identify thrifty alleles in Polynesians, we previously examined evidence of positive selection on T2DM-associated SNPs and identified a T2DM risk allele at unusually high frequency in Polynesians. We suggested that the risk allele of the Gly482Ser variant in the PPARGC1A gene was driven to high frequency in Polynesians by positive selection and therefore possibly represented a thrifty allele in the Pacific.MethodsHere we examine whether PPARGC1A is a thrifty gene in Pacific populations by testing for an association between Gly482Ser genotypes and BMI in two Pacific populations (Maori and Tongans) and by evaluating the frequency of the risk allele of the Gly482Ser variant in a sample of worldwide populations.ResultsWe find that the Gly482Ser variant is associated with BMI in Tongans but not in Maori. In a sample of 58 populations worldwide, we also show that the 482Ser risk allele reaches its highest frequency in the Pacific.ConclusionThe association between Gly482Ser genotypes and BMI in Tongans together with the worldwide frequency distribution of the Gly482Ser risk allele suggests that PPARGC1A remains a candidate thrifty gene in Pacific populations.

Complete Mitochondrial Genome Sequencing Reveals Novel Haplotypes in a Polynesian Population

The high risk of metabolic disease traits in Polynesians may be partly explained by elevated prevalence of genetic variants involved in energy metabolism. The genetics of Polynesian populations has been shaped by island hoping migration events which have possibly favoured thrifty genes. The aim of this study was to sequence the mitochondrial genome in a group of Maoris in an effort to characterise genome variation in this Polynesian population for use in future disease association studies. We sequenced the complete mitochondrial genomes of 20 non-admixed Maori subjects using Affymetrix technology. DNA diversity analyses showed the Maori group exhibited reduced mitochondrial genome diversity compared to other worldwide populations, which is consistent with historical bottleneck and founder effects. Global phylogenetic analysis positioned these Maori subjects specifically within mitochondrial haplogroup - B4a1a1. Interestingly, we identified several novel variants that collectively form new and unique Maori motifs – B4a1a1c, B4a1a1a3 and B4a1a1a5. Compared to ancestral populations we observed an increased frequency of non-synonymous coding variants of several mitochondrial genes in the Maori group, which may be a result of positive selection and/or genetic drift effects. In conclusion, this study reports the first complete mitochondrial genome sequence data for a Maori population. Overall, these new data reveal novel mitochondrial genome signatures in this Polynesian population and enhance the phylogenetic picture of maternal ancestry in Oceania. The increased frequency of several mitochondrial coding variants makes them good candidates for future studies aimed at assessment of metabolic disease risk in Polynesian populations.

'Mutiny on the Bounty': The genetic history of Norfolk Island reveals extreme gender-biased admixture

BackgroundThe Pacific Oceania region was one of the last regions of the world to be settled via human migration. Here we outline a settlement of this region that has given rise to a uniquely admixed population. The current Norfolk Island population has arisen from a small number of founders with mixed Caucasian and Polynesian ancestry, descendants of a famous historical event. The ‘Mutiny on the Bounty’ has been told in history books, songs and the big screen, but recently this story can be portrayed through comprehensive molecular genetics. Written history details betrayal and murder leading to the founding of Pitcairn Island by European mutineers and the Polynesian women who left Tahiti with them. Investigation of detailed genealogical records supports historical accounts.FindingsUsing genetics, we show distinct maternal Polynesian mitochondrial lineages in the present day population, as well as a European centric Y-chromosome phylogeny. These results comprehensively characterise the unique gender-biased admixture of this genetic isolate and further support the historical records relating to Norfolk Island.ConclusionsOur results significantly refine previous population genetic studies investigating Polynesian versus Caucasian diversity in the Norfolk Island population and add information that is beneficial to future disease and gene mapping studies.

Dating nodes on molecular phylogenies: older or younger than the Earth itself?

In his recent critique of molecular biogeography, Heads (2005, p. 66) quotes us (Smissen, Garnock-Jones and Chambers, 2003) out of context and selectively. He wrote: ‘‘For example, Smissen et al. (2003) based node calibrations in Scleranthus (Caryophyllaceae) on fossil ages and concluded that the genus diverged within the last 10 million years , whereas this should have been given as at or before 10 million years ago . (This mistake leads inevitably to others: the authors find themselves forced to admit that Clearly, Scleranthus is capable of long-distance dispersal [from Europe to Australasia, direct!] despite lacking any obvious adaptations to facilitate it .)’’ We agree with Head’s general points that dating nodes in molecular phylogenies is a difficult process of approximation with most data, and that the inadequacy of the fossil record, and the apparent variation in rates of substitution, both among lineages and over time, present major impediments to accurate dating. The limitations of our date estimates, which we feel are honestly and clearly stated for all to read in our paper, were offset by the orders-of-magnitude discrepancies between the sequence divergences we observed and predictions based on vicariance hypotheses explaining the biogeography of Scleranthus. In fact, as is discussed in our paper, our conclusion that Scleranthus is capable of long-distance dispersal is based on the observation that conspecific samples from Australia and New Zealand differ by as little as one substituted site in ITS sequences. Were these populations sundered by the opening of the Tasman Sea, for the sake of argument, this difference of approximately 0.002 substitutions per site (using Kimura 2P distance estimates: Kimura, 1980) yields a substitution rate of the order of 2.0 · 10 substitutions per site per year (conservatively assuming a date 60 Myr before present for this vicariance event). If this was then extrapolated to the tribal-level divergences (around 0.4 substitutions per site) within the Caryophyllaceae that we used as a calibration for our dating, then the Caryophyllaceae are projected to be in excess of 10 billion years old. With regard to the Eurasia ⁄Australasia disjunction in the global distribution of Scleranthus, we did not, as Heads implies, conclude that this was necessarily the product of long-distance dispersal, although we included this as a possible explanation. As we pointed out, it is quite plausible that the range of Scleranthus or its progenitors was once greater than observed today, so that the disjunction could be the result of range reduction, and neither tectonic vicariance nor longdistance dispersal is required. The Mesozoic vicariance events suggested to us by Heads (pers. comm., 1995), however, appear quite inconsistent with the low divergence between sequences from Eurasian and Australasian clades.