A genetic tree as a movie: Moving beyond the still portrait of ancestry

(Press-News.org) ANN ARBOR—University of Michigan researchers have developed a statistical method that can be used for such wide-ranging applications as tracing your ancestry, modeling disease spread and studying how animals spread through geographic regions.

One of the method's applications is to give a more complete sense of human ancestry, says Gideon Bradburd, U-M professor of ecology and evolutionary biology. For example, when you send your DNA off for a personalized ancestry report, the report you get back is only a very small view of your family tree pinned in a specific point and space in time. 

These types of genetic reports reflect the amount of a person's genome that they've inherited from individuals living in a specific area at a specific point in the past. If your ancestry report says that you're 50% Irish, that means you have a lot of second through fourth cousins who currently live in Ireland, says Bradburd. But in reality, your family tree is much more like a movie than this snapshot. 

The statistical method developed by Bradburd and fellow U-M researchers Michael Grundler and Jonathan Terhorst can give people a "movie" version of their ancestry, showing where their ancestors originated and how they moved across the globe. The method uses modern genetic sequence samples, estimates all of the locations of an individual's genetic ancestors, identifies the average location of those individuals based on assumptions about how people move, and tracks it back over centuries.

The researchers' method can be used for more than tracing human ancestry. It can also be used to track the emergence of viruses, the divergence of animal populations and other genealogical tracking. Their results are published in the journal Science.

"There's ways in which consumer ancestry reports are interesting, and certainly it's powerful to learn about your history, especially for folks who've been adopted or orphaned or are disconnected from their family," Bradburd said. "But there are other ways in which these ancestry reports can be really problematic. They really reify notions of the biological essentialism of race because they're presenting these categories of Irish, for example, as if they're ideals, that they're real and unchanging through time."

But researchers know this isn't the case. A field, forged by Nobel Prize-winning geneticist Svante Pääbo, developed the tools to genotype ancient DNA. This allows researchers to trace waves of human populations as they spread throughout the world—particularly in Eurasia, where most of this type of genetic sequencing has been happening, Bradburd says. This has allowed researchers to see how human groups enter and leave geographic regions through time.

"Because the genetic flavor of a location changes so much through time, we know it's meaningless to say, 'This is what it means to be Irish,'" Bradburd said. "It's not just that being 'genetically Irish' doesn't mean anything; it also means that you are everything."

Bradburd points to a thought experiment in human biology: imagine two biological parents and four biological grandparents. This doubles every generation, and it only has to double a relatively small number of generations before there are more people in that direct lineage than there have ever been humans alive on Earth.

This also means that you don't have to go very far back in time to discover that many people share many ancestors.

"Because our pedigrees explode so quickly, they also must collapse in the same sense that you and I must share many, many relatives at many points back in time, and that's true for every person alive on Earth," Bradburd said. "We're all extraordinarily closely related to each other."

The ancestry reports are accurate, Bradburd said, but specifically when they are tied to a time period. 

"The ancestry reports aren't wrong, but they're leaving out a very important component, which is the 'when' you have Irish ancestry," Bradburd said. "Because we know the modern human lineage arose in Africa, it is as accurate to say that you have 100% African ancestry at a deeper time horizon."

The statistical method, called Gaia (geographic ancestry inference algorithm), starts by making a very simple assumption about how individuals move: that typically they move locally. The method combines that assumption with the location of modern-day individuals and a genetic structure that relates them called the ancestral recombination graph.

With those two pieces of information and the simple model of how individuals move, the researchers can compute the "most parsimonious locations of ancestors," Bradburd says. The researchers then can propagate that information back through the past.

Bradburd's work is answering a call from the National Academy of Sciences, urging researchers working on human population genetics to move away from race-based labels. While the sociological realities of race are undeniable, racial categories do not make good predictions about genetic variation, he says.

Because of the disconnect between race and genetics, racial labels can often be imprecise: two people might share the same label, but be much more closely or less closely related to each other. In addition, because the genetics in a certain geographic area can shift so much over time, geographic and national labels can also be misleading, Bradburd says. 

"Saying you're 'genetically Irish' makes it seem like 'Irish' has always meant the same thing, and genetically we know that is not true and also that anyone who is Irish—meaning they inherited parts of their genome from people who lived in Ireland—is only Irish with respect to a specific time horizon," he said. "That these race labels gloss over both of these important pieces of information is a big loss of specificity and also poses a very real danger to the weaponization of science for political means."

The method Bradburd's team developed can be applied to systems other than human genetics. Researchers can use this method to look at the genetic distribution of the organisms they study. Researchers can also use this method to learn about the migration of organisms—human and otherwise, Bradburd says.

For example, researchers have been able to look at measures of genetic similarity of population between two locations and infer that they are more or less closely connected by migration, or more or less isolated from each other. But this tool allows researchers to pin a timeline on when these movements happened.

And this tool can apply in this case to more than tracing human genetics—it can be used to help determine when a disease might have emerged from a specific region of the world, for example. The U-M group is working with researchers in Australia to learn how mosquitoes colonized islands of the South Pacific, and with researchers in Michigan and Ohio to understand the history and dispersal of the Massasauga rattlesnake.

"It's one of the things I'm quite excited about with this—you can use this method to identify dispersal patterns through time and between specific locations," Bradburd said. "Notions of ancestry don't have to be static. Instead, you should think of them as being dynamic, and interesting and understandable more as a movie than as a picture."

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