Genetic Detectives

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
Amazon.com 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?'”

This article appears in Dec 10-16, 2009.