NEW YORK (GenomeWeb News) – Three new genomic studies are providing clues about relationships between populations around the world, highlighting the relationships and genetic diversity that exists within and between human populations.
Two of the papers appeared in Nature yesterday, while a third appeared in today’s edition of Science. The research supports the previously held notion that humans originated in East Africa, migrating outward until they reached all parts of the globe. But the genetic work brings a new level of precision to human migration studies, with each group finding subtle and intriguing details that shed light on different aspects of human genetic variation and ancestry.
The first study, led by University of Michigan geneticist, biostatistician, and evolutionary biologist Noah Rosenberg and National Institute of Aging molecular geneticist Andrew Singleton, was based on the analysis of more than 500,000 SNPs and nearly 400 copy number variants — sections of DNA that are repeated or duplicated in the genome — for 485 individuals. These samples, representing individuals from 29 different populations around the world, were obtained as part of the Human Genome Diversity Project.
After genotyping the samples using Illumina Infinium HumanHap550 BeadChips, they compared their results to haplotype clustering data created using fastPHASE software as well as copy number variation data. Though there were subtle differences depending on the type of analysis, their results reveal serial founder effects in human populations. In other words, as human populations moved further and further from East Africa, each group ended up with a smaller overall number of genetic changes — a subset of those that once existed in the founder population.
For instance, the research suggests East Africans are the most genetically diverse, while Native American genomes exhibit the lowest genetic diversity. Middle Eastern, Asian, and European populations, on the other hand, fall somewhere in between. “Diversity has eroded through the migration process,” Rosenberg explained.
By following this decline in diversity, the team was able to retrace global human migration patterns. Consistent with previous archeological date, language studies, and smaller genetic studies of mitochondrial DNA or autosomal or sex chromosomes, the research suggests humans originated in Africa, migrating first to the Middle East, then to Europe, Asia, the Pacific Islands, and — eventually — the Americas.
A second study, also appearing in Nature, found similar genetic diversity in those of African descent. Co-senior authors Carlos Bustamante, a biostatistician and computational biologist at Cornell University, and Andrew Clark, a Cornell University molecular biologist and geneticist, and their colleagues used comparative genomics to analyze 39,440 autosomal SNPs in 10,150 sequences from 15 African-Americans and 20 European-Americans.
Using the PolyPhen computer algorithm, they also assessed how many of the nucleic acid changes in each population were likely to produce amino acid changes that were “possibly” or “probably” damaging.
Surprisingly, while they found that the overall genetic diversity was higher in those of African descent, they found that those of European descent had more genetic variations that were predicted to be damaging. The authors attribute this to differences in population age and suggest European populations may have undergone a more recent population bottleneck — a decrease in population that leads to the selection of certain genetic traits — than their African ancestors.
“Since we tend to think of European populations as quite large, we did not expect to see a significant difference in the distribution of neutral and deleterious variation between the two populations,” Bustamante said in a statement.
Finally, in the largest of the three studies, a group of researchers based primarily at the Stanford Human Genome Center assessed 642,690 SNPs from 938 individuals from 51 populations. Their results, published today in Science, provide a peek into the genetic variation both on a global scale as well as within relatively small geographic areas.
“By measuring the genetic variation at each of the loci — which is now made possible by very recent technology to do this fast and cheap and accurately — we were able to get a picture of the genetic differences and similarities between people in these populations from around the world in much, much, much greater detail than had been measured before,” senior author Richard Myers, a geneticist at Stanford University said in Science magazine’s weekly podcast.
Like Rosenberg and Singleton’s group, the team relied on samples collected through the Human Genome Diversity Project. Again, they found the highest genetic diversity in sub-Saharan Africa. Specifically, they found evidence for decreasing haplotype heterozygosity in populations as they moved further and further away from Addis Ababa, Ethiopia.
They also found genetic evidence for differences in ancestry within populations. For instance, some individuals from the Middle East, such as Palestinians, Druze, and Bedouins, had ancestors from the Middle East as well as Europe and parts of South and Central Asia.
The results of these studies, while intriguing from a human ancestry perspective, may also provide insights into interpreting the genetics of some diseases, since they provide a framework for understanding genetic variation.
“One of the biggest problems … is that when you don’t take population or geographic origin into account in a large genetic study for studying something like heart disease — one of the complex traits — for instance, you end up confounding the study such that you don’t actually get real signals,” Myers said in the Science podcast.