Feature: Genetic diversity and human evolution

Read part I of this feature, Exploring the bounds of human genetic diversity.

The greatest surprise to come out of Vanessa Hayes’ study of human genetic diversity was the sheer magnitude of the diversity within the African Bushmen population itself.

Hayes was certainly expecting to see a higher number of variants in the Bushmen genomes; in fact !Gubi, the individual who had his whole genome sequenced, had four million DNA variants, compared to the three million of Craig Venter and two million of James Watson. According to Hayes, this is due to the genetic isolation of the Bushmen, who have had time to accumulate more variants than the more recent European lineages.

But she wasn’t expecting to see such diversity amongst the Bushmen themselves. “What was unexpected was that two bushman, !Gubi and G/aq’o, who live 800 kilometres apart, had more differences between each other than a European has from an Asian. I knew there would be differences, but I didn’t know it would be that extreme.”

The cause of this tremendous diversity simply comes down to isolation. “We think these populations diverged from a common ancestor around 100,000 years ago, so they’ve effectively been living in genetic isolation for 100,000 years,” says Hayes.

“Therefore the difference between these two populations is so great because of their isolation from each other, and from the rest of Africa. Although 800 kilometres is not a lot for us, it’s huge difference for someone who’s a hunter-gatherer. They typically don’t move more than 100 kilometres from where they grow up because they survive off the land and the land changes so dramatically.”

The take home message of this insight into genetic diversity? “The most important thing we learned from this genome is that we are one species, and have to start thinking of ourselves as that, and stop thinking of ourselves as European-centric,” says Hayes.

“If we do that, we won’t understand disease for everybody. For example, !Gubi has variation that appears in the mutation database which says he should not have lived past five years old. Yet here is a man who is about 85 years old, running around the bush, as healthy as can be, has never been to a doctor in his life and even I can’t keep up with him.

“My argument is if we can sequence indigenous people around the world, and start remembering that we are one species that has populated the globe, we can actually start making sense of these databases that we have. We can start making sense of what is phenotypically relevant. We could learn a lot from each other.”

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Genetics the right way around

The southern African genome project, published in Nature in February 2010, stirred up a great deal of interest and garnered a lot of attention for Hayes, with job offers crop- ping up all over the globe.

One of those who took notice was Craig Venter, who presented Hayes with an offer she couldn’t refuse. She’s now heading up the genomics medicine group at the J Craig Venter Institute with a mandate from Venter to continue “doing what she does best”: exploring the extent of human diversity.

But not only the extent of genetic diversity, but also linking that genetic diversity to phenotypic diversity. “The original study that I did was just touching the tip of the iceberg,” says Hayes.

The next step is to explore other populations in Africa and around the world to get a better handle on the extent of genetic diversity, and to start shedding light on things like the story of human migrations around the world throughout history.

Understanding genetic diversity should also lend insights into human disease and disease susceptibility. And this means doing genetics in a slightly different way, says Hayes.

Instead of starting with genotypes and then looking for differences in phenotypes, Hayes suggests we should also be approaching studies from the opposite perspective: looking for extremes in phenotype and only then embarking on a sequencing project.

Using this global genomics approach, her hope is we should be able to gain a better understanding of the true extent of phenotypic and genetic diversity.