Researchers gain genome-wide insights into patterns of the world's human population structures

Deep mining of data offers information on human evolution and relationships among populations.

Through sophisticated statistical analyses and advanced computer simulations, researchers are learning more about the genomic patterns of human population structure around the world.

Revealing such patterns provides insights into the history of human evolution, the predominant evolutionary forces that shaped local populations, and the relationships among populations.

"Studying genomic patterns of human population structure also has practical applications in disease-gene mapping," noted Dr. Joshua M. Akey, University of Washington (UW) assistant professor of genome sciences. Akey is senior author of new genomic research findings about the fine-scale structure of diverse human populations. The results will be published May 15 in the American Journal of Human Genetics. The lead authors were Shameek Biswas and Dr. Laura B. Scheinfeldt, both of the UW Department of Genome Sciences.

A statistical method called principle component analysis allows researchers to look through a thick, voluminous fog of genetic data and see significant variations. The UW researchers applied this method to a data set of almost 650,000 SNPs (pronounced "snips").

A single nucleotide polymorphism is a genetic variation in which the DNA code differs by only one "letter" in the same DNA sequence from two individuals of the same species. The data set of 650,000 SNPs came from 944 unrelated persons representing 52 broadly classified populations living in several regions on seven continental groups: Africa, America, Central and South East Asia, East Asia, Europe, Middle East, and Oceania. This global sampling came from The Human Genome Diversity Project - Center for the Study of Human Polymorphisms

Most previous genomic studies of this nature have focused on broad-scale patterns of structure among geographically diverse populations, the UW researchers noted. These studies concluded that 85 to 95 percent of human genetic variation can be attributed to differences among individuals, and 5 to 15 percent is due to differences between populations.

In contrast to these broad-scale patterns, more recently researchers have tried to look at fine-scale population structure. Usually these studies focus on only the two or three top- ranking axes of genetic variation emerging from the statistical analysis. For example, studies of European individuals have shown a strong correlation between the top two axes of genetic variation and the actual geographical location of the sampling.

In their newly published findings, UW researchers demonstrated that substantial information on population structure is hidden more deeply in the genomic data. They were able to identify 18 significant, informative axes of variation. Some of these distinguished particular populations.

The UW researchers also conservatively estimated the set of all of the SNPs, or specific, tiny DNA code differences, matching each of the most informative axes of variation. These variations represent numerous fixed positions on the human genome where different biomarkers can sit and thereby form a "genomic signature" of population structure. They also allow for more detailed inferences, the UW researchers noted, about the evolutionary forces that shape the fine-scaled patterns of human population structure.

"The genome-wide distribution of these markers," Akey believes, "can largely be accounted for by genetic drift." Genetic drift is gradual accumulation of random changes in the gene pool of small populations. Akey added that some of these variations, however, do cluster in regions of the human genome considered to be targets of recent adaptive evolution.

The researchers also observed patterns of human genetic variation that correlated with geography in essentially every continental group. While such geographical patterns have been described in European samples, the researchers think that the extent to which such geographic correlations might be found in other continents may not be fully appreciated.

In mentioning the limitations of his study approach, Akey cautioned that there are still questions about the best way to design human population genetics research in terms of sampling individuals and populations, but that progress is likely.

"Now that we have increasingly dense catalogs of genetic variation," Akey wrote, "the details of human population structure are becoming more tractable. The testing of increasingly refined hypotheses about human population structure should yield new insights into the history and relationships among human genomes."

Eurekalert 2009.

High population density triggers cultural explosions

Increasing population density, rather than boosts in human brain power, appears to have catalysed the emergence of modern human behaviour, according to a new study by UCL (University College London) scientists published in the journal Science. High population density leads to greater exchange of ideas and skills and prevents the loss of new innovations. It is this skill maintenance, combined with a greater probability of useful innovations, that led to modern human behaviour appearing at different times in different parts of the world.

In the study, the UCL team found that complex skills learnt across generations can only be maintained when there is a critical level of interaction between people. Using computer simulations of social learning, they showed that high and low-skilled groups could coexist over long periods of time and that the degree of skill they maintained depended on local population density or the degree of migration between them. Using genetic estimates of population size in the past, the team went on to show that density was similar in sub-Saharan Africa, Europe and the Middle-East when modern behaviour first appeared in each of these regions. The paper also points to evidence that population density would have dropped for climatic reasons at the time when modern human behaviour temporarily disappeared in sub-Saharan Africa.

Adam Powell, AHRC Centre for the Evolution of Cultural Diversity, says: "Our paper proposes a new model for why modern human behaviour started at different times in different regions of the world, why it disappeared in some places before coming back, and why in all cases it occurred more than 100,000 years after modern humans first appeared.

"By modern human behaviour, we mean a radical jump in technological and cultural complexity, which makes our species unique. This includes symbolic behavior, such as abstract and realistic art, and body decoration using threaded shell beads, ochre or tattoo kits; musical instruments; bone, antler and ivory artefacts; stone blades; and more sophisticated hunting and trapping technology, like bows, boomerangs and nets.

Professor Stephen Shennan, UCL Institute of Archaeology, says: "Modern humans have been around for at least 160,000 to 200,000 years but there is no archaeological evidence of any technology beyond basic stone tools until around 90,000 years ago. In Europe and western Asia this advanced technology and behaviour explodes around 45,000 years ago when humans arrive there, but doesn't appear in eastern and southern Asia and Australia until much later, despite a human presence. In sub-Saharan Africa the situation is more complex. Many of the features of modern human behaviour – including the first abstract art – are found some 90,000 years ago but then seem to disappear around 65,000 years ago, before re-emerging some 40,000 years ago.

"Scientists have offered many suggestions as to why these cultural explosions occurred where and when they did, including new mutations leading to better brains, advances in language, and expansions into new environments that required new technologies to survive. The problem is that none of these explanations can fully account for the appearance of modern human behaviour at different times in different places, or its temporary disappearance in sub-Saharan Africa."

Dr Mark Thomas, UCL Genetics, Evolution and Environment, says: "When we think of how we came to be the sophisticated creatures we are, we often imagine some sudden critical change, a bit like when the black monolith appears in the film 2001: A Space Odyssey. In reality, there is no evidence of a big change in our biological makeup when we started behaving in an intelligent way. Our model can explain this even if our mental capacities are the same today as they were when we first originated as a species some 200,000 years ago.

"Ironically, our finding that successful innovation depends less on how smart you are than how connected you are seems as relevant today as it was 90,000 years ago.

Eurekalert 17/06/09

New 'molecular clock' aids dating of human migration history

Researchers at the University of Leeds have devised a more accurate method of dating ancient human migration – even when no corroborating archaeological evidence exists.

Estimating the chronology of population migrations throughout mankind's early history has always been problematic. The most widely used genetic method works back to find the last common ancestor of any particular set of lineages using samples of mitochondrial DNA (mtDNA), but this method has recently been shown to be unreliable, throwing 20 years of research into doubt.

The new method refines the mtDNA calculation by taking into account the process of natural selection - which researchers realised was skewing their results - and has been tested successfully against known colonisation dates confirmed by archaeological evidence, such as in Polynesia in the Pacific (approximately 3,000 years ago), and the Canary Islands (approximately 2,500 years ago).

Says PhD student Pedro Soares who devised the new method: "Natural selection's very gradual removal of harmful gene mutations in the mtDNA produces a time-dependent effect on how many mutations you see in the family tree. What we've done is work out a formula that corrects this effect so that we now have a reliable way of dating genetic lineages.

"This means that we can put a timescale on any part of the particular family tree, right back to humanity's last common maternal ancestor, known as 'Mitochondrial Eve', who lived some 200,000 years ago. In fact we can date any migration for which we have available data," he says.

Moreover, working with a published database of more than 2,000 fully sequenced mtDNA samples, Soares' calculation, for the first time, uses data from the whole of the mtDNA molecule. This means that the results are not only more accurate, but also more precise, giving narrower date ranges.

The new method has already yielded some surprising findings. Says archaogeneticist Professor Martin Richards, who supervised Soares: "We can settle the debate regarding mankind's expansion through the Americas. Researchers have been estimating dates from mtDNA that are too old for the archaeological evidence, but our calculations confirm the date to be some 15,000 years ago, around the time of the first unequivocal archaeological remains.

"Furthermore, we can say with some confidence that the estimate of humanity's 'out of Africa' migration was around 60-70,000 years ago – some 10-20,000 years earlier than previously thought."

The team has devised a simple calculator into which researchers can feed their data and this is being made freely available on the University of Leeds website.

Eurekalert 17/06/09