Genetic Detectives

Want to find out where you fit on the human family tree? The UA's Human Origins Genotyping Laboratory is on the case

Matt Kaplan and I go way back—some 10,000 years or so, according to our common Y chromosome.

Kaplan, the director of research at the UA's Human Origins Genotyping Laboratory, and I are both members of Y chromosome haplogroup J2 (M172), which means we—like every other human male alive today—had a common ancestor somewhere around northeast Africa's Rift Valley roughly 60,000 to 100,000 years ago, according the best guess of some scientists. Our Y chromosome ancestor, along with his traveling companions, left Africa approximately 50,000 years ago. That man ended up being the ancestor not only of Kaplan and me, but of all non-African males alive today.

How did one man end up as the Eurasian Adam when there were an estimated 10,000 Homo sapiens walking the Earth? Kaplan says it's because the Y chromosome is only passed down from father to son, and subtle mutations on the chromosome make it an ideal tracker for following the migration of mankind across the globe.

"Every generation, some men don't have sons," Kaplan says. "That's the end of their Y chromosome line. They may have daughters, so it's not like all of their genetic lines are dying out. It's just the lineage of the Y chromosome."

Women carry a similar genetic marker, their mitochondrial DNA. It is handed down only by a mother to her children; since her sons will not pass it on, the mitochondrial line allows scientists to track maternal lines back in time.

My paternal ancestors migrated into the Middle East 40,000 years ago and settled somewhere in the Fertile Crescent between the Mediterranean Sea and the Persian Gulf.

"Back that deep in time, pretty much everyone was a hunter-gatherer," Kaplan says.

But sometime over the next 30,000 years, our ancestors were among the people who first learned how to grow food along the floodplain of the Euphrates and Tigris rivers.

"When I think J2, it's the origin of agriculture," Kaplan says.

The launch of agriculture also played a key role in the building of towns and cities, and the birth of civilization as people settled into one place and developed more complex social relationships.

About 10,000 years ago, people from my genetic line moved north into the Mediterranean region, including southern Italy and southern Spain, while others expanded across north Africa.

"When I meet Europeans who are J2s, it speaks usually to Middle Eastern or Mediterranean ancestry," Kaplan says. "My first guess usually is, 'Oh, you're Eastern European Jewish.' Another way to have it is to be of Mediterranean ancestry. You have your Italians and that whole part of Europe."

With my shaky understanding of my family tree on my father's side—I've always heard it was some mix of German, French and English—I can't say how the J2 marker got into my genes, but one of my ancestors must have continued to be a man on the move in the roughly 10,000 years between the end of my genetic test's history and today.

I'm one of more than 300,000 people across the globe who have swabbed the inside of their cheeks and sent the cells in to the Genographic Project, an ambitious international effort of the National Geographic Society and IBM that hopes to put together an ever-growing database of DNA samples to better understand the migrations of humans tens of thousands of years ago.

The Genographic Project grew out of The Journey of Man, a book and documentary film by population geneticist Spencer Wells that tracked down Y-chromosomal Adam—the most recent common ancestor of all men now on the planet, who likely lived in Africa 60,000 to 100,000 years ago—and Mitochondrial Eve, the most recent common ancestor of all women on the planet, who lived in Africa an estimated 150,000 years ago.

"The Genographic Project is the next step," Kaplan says. "It's not just the academic experience. Now it can be the journey of you. It's one thing to read about prehistory or watch a movie about prehistory, but it's a whole other dimension to say, 'Where do I fit into this living, breathing database?'"

Using a kit that costs about $100, participants in the Genographic Project can uncover their own genetic odyssey by scraping the inside of their cheek with a small brush that's deposited into a vial and dropped into the mail to the National Geographic Society.

The samples all end up right here at the UA's Human Origins Genotyping Laboratory, located not far from University Medical Center in the Thomas W. Keating Bioresearch Building that also serves as headquarters for the BIO5 Institute.

Each week, anywhere from 1,200 to 4,000 of the vials arrive at the lab. A crew of undergraduates zap each one with a scanner gun. A computer program tells the students how to place the sample into a square rack and records the coordinates so the computer will be able to track the samples through the rest of the testing process.

The samples will be injected with an enzyme to break the cheek cells down before they're mixed with silica, washed in several chemical baths, diluted to a standard level and heated repeatedly until a DNA strand unzips and begins copying itself. The samples are then filtered through a sequencer that delivers a colorful report that can unlock the codes that reveal deep ancestry.

While the undergraduates do their share of grunt work, most of the steps are performed by state-of-the-art robots that have been customized to handle the task of tracking hundreds of thousands of samples. Various safeguards have been built into the process to indicate if something has gone astray. The system is so sophisticated that if a problem arises, a text message goes out to lab workers, who can then check the lab via a remote camera.

"We have a very agile, very creative computing group who really make the most out of our robotics," says Kaplan.

That means that researchers don't have to spend as much time processing their samples.

"There's a lot less stupid time spent with Excel spreadsheets filled with samples and more time spent looking at results," Kaplan says.

The Genographic Project is the Human Origins Genotyping Laboratory's biggest client and provides the volume of work that made construction of the new lab possible. But the lab also serves a wide range of clients as one of the top commercial DNA labs in the world.

Taking advantage of advances in technology, the lab, which is part of the UA's Arizona Research Laboratories, has come a long way from a small unit in the BioWest Building under the leadership of Michael Hammer, who has spent nearly two decades developing the UA's genetics program. One of the lab's first clients was Family Tree DNA, a private company that has developed an extensive database that helps people determine their genealogical background.

In the lab's earlier days, workers tried to adapt labs to accommodate new equipment by drilling holes through countertops, remembers senior research specialist Barbara Fransway.

Fransway is the laboratory supervisor for the DNA Shoah Project, which seeks to use genetic links to connect families who were separated in the Holocaust and educate future generations about the horrors of the Nazi extermination project.

"The main goal is to reunite families that were separated in the Holocaust, but that's not an easy task," Fransway says. "We're racing against time."

In conjunction with the DNA Shoah Project, Fransway is working with students from Palo Verde High School. Earlier this year, the school won a $265,000 Innovations in Education grant from Hewlett-Packard. Students will have a chance to get hands-on experience analyzing DNA samples of Holocaust survivors as part of Palo Verde's Annealing Project, which will also include interviews with Holocaust survivors and the development of an online archive.

"It allows them to contribute to an ongoing scientific project," Fransway says.

Fransway, who sees helping kids get engaged in science as part of the lab's mission, also teaches a one-week CSI class every summer that helps high school students understand how law-enforcement agencies use DNA to nab criminals. Her efforts led to her being named the 2009 Bioscience Educator of the Year by AZBio, a consortium of business, research, education and government organizations involved in the state's bioscience industry.

Fransway shares a cubicle with Taylor Edwards, an assistant staff scientist who helps manage the flow of DNA testing at the lab.

A conservation biologist by training, Edwards has spent years studying desert tortoises and serves as the outgoing president of the Tucson Herpetological Society.

"I have an affinity for working with creepy-crawly critters," says Edwards, who is now using the lab to conduct tests on tortoise DNA to better understand its range and breeding patterns.

"When you start studying something like that, that lives for so long, and you want to ask questions about how often they move between mountain ranges, it's too long of a time scale," Edwards says. "DNA was the way to go, because you can look at past histories of gene flow and learn if different populations share genes or if they are distinct from each other."

With just a small blood sample, Edwards can learn how different tortoise populations are related. His hypothesis: There are three distinct species of desert tortoise: the Mojave desert tortoise, a Sonoran desert tortoise and a Sinaloan desert tortoise.

"That kind of taxonomy is relevant to conservation, because if you think something has a range that's this big, and all of a sudden, you realize that what you're trying to conserve has a smaller range, it changes your strategies a little bit, because you have fewer individuals than you thought you did," he says.

This new kind of conservation biology has also lured Hans-Werner Herrmann to the lab. Herrmann, a German native who has long been fascinated by reptiles and amphibians, is conducting a range of studies, including surveys of the genetic makeup of the endangered Chiricahua leopard frog.

"Some of the populations have disappeared completely, and others are in urgent need of help," says Herrmann, who works with a small statue of Darwin looking over his shoulder. "So before we take action, we need to understand what's happening on the ground."

By testing the genetic makeup of the leopard frogs, Herrmann can help Arizona Game and Fish officials decide the best way to combine dwindling populations of the tiny amphibian.

Herrmann is also working on a study of three different rattlesnake species in the Picacho Peak area to learn how manmade barriers such as Interstate 10 and the Central Arizona Project canal have fragmented habitats.

He and his team go out on summer nights and capture rattlesnakes, place microchips in them for tracking purposes and draw a small sample of blood for DNA testing to better understand how the snakes are related.

Herrmann next hopes to launch a project with the United Nations to track the origins of bushmeat in Africa. Bushmeat, which is meat from wild animals that is sold in markets for human consumption, often includes endangered species.

If he can secure United Nations funding, Herrmann hopes to travel to markets in Africa to take samples that will be linked to a GPS signal. Then he hopes to follow the trail of the bushmeat's DNA into smaller markets to better understand what animals are being captured and where they are being hunted. With genetic data, he will be able to identify which species are doing fine and which are being over-hunted. Ultimately, he hopes to develop an extensive database that will help African officials better manage wildlife.

It's an ambitious—and expensive—undertaking.

"It helps that the biotechnology field takes giant steps," Herrmann says. "In the last decade, we had a drop in the cost of gene sequencing of four orders of magnitude."

Kaplan, who traveled to Cameroon last year to get a first-hand look at the bushmeat crisis, says the project's real goal is "sustainability and letting scientists say, 'Yes,' because right now, bushmeat is regulated in the just-say-no fashion. Maybe we can say: You know what? Why don't you leave the mountain gorillas and the chimps alone, and why don't you eat the—they call them grass cutters, which are these big rats."

That, in turn, would allow African officials to better direct limited resources.

"Enforcement would be better-suited on things that matter, with a lot less effort directed toward things that don't," Kaplan says. "Our goal is not to come in and tell people what to do. ... We just wish to help, and in our field, we can do that by providing genetic data."

Besides its efforts in conservation biology, the lab is moving in other directions, including work with transgenic mice and whiteflies to help scientists conduct research.

To better aid clients, a sister laboratory, the University of Arizona Genetics Core, is developing an online shopping cart similar to so researchers can electronically order data sorted in different ways.

It's all cutting-edge science, but Kaplan suggests it can be pretty simple at the end of the day.

"We do a lot of really high-tech stuff and have all these robots and lasers," Kaplan says. "On the other hand, we move a lot of tiny volumes of clear liquids from one tube to another, and we heat it up, and we cool it down, and something happens, we hope."

The UA's Human Origins Genotyping Laboratory does the DNA analysis for public participants in the Genographic Project, which lets people around the world take a genetic test to learn their place on the human family tree.

The Genographic Project grew out of The Journey of Man, a book and documentary film by population geneticist Spencer Wells that traced the migration of mankind out of Africa and across the globe using markers in the Y chromosome for men, and in the mitochondrial DNA for women. The above map shows the migration of the Y chromosome in blue, and mitochondrial DNA in orange.

"The Genographic Project is the next step," says Matt Kaplan, director of research at the Human Origins Genotyping Laboratory. "It's not just the academic experience. Now it can be the journey of you. It's one thing to read about prehistory or watch a movie about prehistory, but it's a whole other dimension to say, 'Where do I fit into this living, breathing database?'"


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