An international team contributed to the research, which compared the DNA sequences of 35 modern people living on islands off the coast of New Guinea with DNA drawn from two early human species: Denisovans, whose remains were found in Siberia, and Neandertals, first discovered in Germany.

“Substantial amounts of Neandertal and Denisovan DNA can now be robustly identified in the genomes of present-day Melanesians, allowing new insights into human evolutionary history,” they write. “As genome-scale data from worldwide populations continues to accumulate, a nearly complete catalog of surviving archaic lineages may soon be within reach.”

Andrew Merriwether, a molecular anthropologist at Binghamton University, collected the modern-day blood samples used in the study about 15 years ago in Melanesia. This is the first time full genomes from those samples have been sequenced.

“I’m surprised that these Neandertal and Denisovan genomes made it out to this remote place,” he says. “We know people have been there for at least 48,000 years because we find human remains that go back that far, but no one has ever been able to connect them to any other place. When you compare most of their genome sequences, they don’t cluster with any other group. They’ve been there and been isolated for a very, very long time.”

Earlier studies have revealed some genetic overlap (about 2 percent) between Neandertals and non-African populations and little or no Neandertal and Denisovan ancestry among Africans. This new research suggests Neandertals and modern human ancestors intersected at least three times. It also found an overlap of between 1.9 and 3.4 percent in the genetic codes of Denisovans and modern-day Melanesians.

Skepticism about the new findings is entirely appropriate, says Merriwether, who specializes in reconstructing the past using samples from contemporary populations and ancient DNA from the archaeological record.

“Ancient DNA is always damaged and broken into small pieces,” he explains. “You only need one molecule of modern DNA to outperform all the ancient DNA.”

An independent laboratory did the sequencing of Merriwether’s samples. That, combined with a powerful new statistical technique that was used in the analysis, finally convinced him that the genetic similarities were real.

The cost and time involved in sequencing a full human genome has dropped dramatically. The first, completed in 2003, took 13 years and cost about $2.7 million. Today, it’s possible to sequence a sample in days for thousands of dollars. Still, this type of research still poses significant challenges.

The human genome contains about 3 billion “letters,” and ancient samples are difficult to work with. When people die, their DNA starts breaking down immediately, Merriwether notes, and it isn’t repaired anymore. Normally, a person’s DNA is fixed thousands of times a minute. Bacteria and fungi contaminate most DNA samples taken from human remains, he says, making up as much as 97 percent of the DNA that’s recovered.

Even collecting the modern samples wasn’t a simple task.

Merriwether and longtime collaborator Jonathan Friedlaender of Temple University obtained blood samples throughout the Bismarck Archipelago in the late 1990s and early 2000s. They traveled with George Koki of the Institute for Medical Research in Papua New Guinea and Heather Norton, then a student at Penn State and now a faculty member at the University of Cincinnati.

“It’s challenging to reach these places,” Merriwether says. “They’re volcanic islands with mountains. It’s also the most linguistically diverse place on Earth.”

How diverse? People in this region speak some 800 languages. A common trading language (Tok Pisin) that’s a mix of Polynesian and English helped make it possible for the anthropologists to communicate with residents.

Because malaria is so prevalent in the region, there are many clinics set up to test and treat people. That also meant Merriwether and his colleagues usually weren’t the first people asking residents of these islands for blood samples.

Studies like this one may enable scientists to answer big questions about human migrations and evolution thousands of years ago.

Merriwether is particularly fascinated by the Denisovan DNA fragments found in the Melanesian genomes. How did ancient humans travel — and cross the ocean — to get to Melanesia and when and where did the Denisovan DNA enter our gene pool? Sequencing of additional DNA samples found in Asia may one day help to answer those questions.

“Most people know back a few generations, maybe five generations,” Merriwether says, “but where did we come from before that? That’s what we want to find out.”

The study’s authors are based at Binghamton University, the University of Washington, the University of Ferrara in Italy, the Max Planck Institute for Evolutionary Anthropology in Germany, the University of Cincinnati, the Coriell Institute for Medical Research, the Institute for Medical Research in Papua New Guinea and Temple University.

Senior Alice Cheung’s dedication to her studies and research is evident through more than just her 4.0 grade point average in cellular and molecular biology. “I was really intrigued by being able to focus on one part of the science,” she says, “and finding out something that no one else has done before.”

Cheung, who is originally from Queens, began her research experience at Binghamton in the lab of anthropologist J. Koji Lum. Lum, who has worked with more than 100 undergraduate researchers, says Cheung stands out for her hard-working attitude and ability to learn quickly.

The project was a collaboration of researchers in anthropology, geology and biology. Cheung’s role was to characterize gypsum crystals according to the microdiversity trapped inside of the salt during its formation. The identification of these organisms would provide the team with information about what the environment was like when that crystal formed. The team then used the same technique and applied it to ancient crystals, hoping to find more clues about what life was like millions of years ago.

The team’s abstract was published in The Geological Society of America Abstracts with Programs. Cheung also presented her findings at an international conference, a rarity among undergraduate researchers.

In the lab, Cheung would extract and sequence DNA from the modern crystals and compare her results with her partner, a geology major, who confirmed the findings under the microscope. When they looked at the ancient crystals, however, they weren’t able to find the same results.

Lum and his team of graduate researchers discovered that what they were originally looking for could not be found. “Although her project did not turn out as hoped,” Lum says, “I think it was a valuable lesson in how science often really works.”

In science, a dead end is really more like an open door. Cheung learned that lesson firsthand when she began working in a new lab with Steven Tammariello, an associate professor of biology. His team uses DNA from horse hair samples to screen for desirable genetic traits.

Cheung is trying to find the short fragment of DNA that codes for jumping ability in horses. The offspring of horses that can jump do not necessarily share the trait, so this science could eventually help horse buyers determine if a horse will be a good fit.

This same science can be applied to sequencing human DNA. Scientists are now able to screen DNA to see if someone is prone to diseases such as Alzheimer’s, which can help a person seek appropriate and timely treatment.

“I did research to help me decide what it was I wanted to do in life,” Cheung says.

And it did just that. Cheung plans to attend medical school and continue participating in research.

D. Andrew Merriwether ambles into his lab wearing a green T-shirt, a weathered Binghamton University ball cap and a graying ponytail. He ignores the birthday cake on the bench (chocolate frosting with peanut butter cups) and pulls up a stool.

He has been doing some fieldwork, he says. For this particular molecular anthropologist, that means he was actually in the field — with his alpaca.

He’s looking for genetic links that cause choanal atresia — a disorder found in both the alpaca and humans in which tissue or bone blocks nasal passages. It’s frequently fatal among the alpaca because babies with the condition can’t breathe while nursing.

Choanal atresia has perhaps 20 causes, Merriwether says. Only a couple may be genetic, but understanding the genetics may lead to strategies for prevention or early diagnosis in humans.

That’s a small part of how the alpaca play into his research. “They’re just so neat: curious, quick, smart,” he says. “They survive on almost nothing.”

As a species domesticated by early South American populations, they reflect the culture of the people about whom Merriwether did his dissertation 20 years ago. “For the poorest people of South America, it’s their only source of cash income,” he says. Like those people, Merriwether and his wife shear their alpaca herd.

Genetically, the alpaca had to adapt to life in the 13,000-foot altitudes of the Andes just as people did, says Professor Ralph Garruto, a National Academy of Sciences member whose presence at Binghamton drew Merriwether to the faculty in 2003. How they did that is a question with implications for cultures across the world.

“How do people who are genetically different adapt to the same stressors?” Garruto asks. Women in most parts of the world can’t carry a fetus to term above 10,000 feet, but the people of the Andes do it routinely — as do the alpaca. “All the changes in the alpaca help us see the mechanism in that animal and whether there are parallels in humans. We’re talking survivability and functionality of human beings.”

The alpaca aren’t Merriwether’s sole focus. About a third of his research lies in Melanesia, with the peoples of New Guinea and the Bismarck Archipelago. He has many of the same questions he had about the South American cultures that got him into molecular anthropology in the first place: How did they get there? How long ago? How have they adapted?

“Almost every question I am interested in,” he notes, “has DNA as a way of answering it.”

Binghamton University biologist Heather Fiumera thinks that some of those health problems may lie in the fact that mitochondrial function requires the cooperation of two different genomes. Every human inherits two genomes: one in the cell’s nucleus, which is a mix of mom and dad’s DNA, and a different one in the mitochondria (the cell’s powerhouse), which contains a replica of mom’s mitochondrial DNA. “It may be that some combinations of mitochondrial and nuclear genomes work together more efficiently than others,” Fiumera says. “While mutations in either genome may affect mitochondrial function, they don’t explain the whole story. You might inherit a mitochondrial genome that helps you become a world-class marathon runner, but your brother” — who would have the exact same mitochondrial genome as you — “might not be as successful, even with the same training.” Similarly, a mitochondrial mutation may cause a severe metabolic disorder in one sibling, but mild symptoms in another, because of how the mitochondrial mutation interacts with their different nuclear DNAs.

Fiumera and her colleagues received a $1.25 million award from the National Institutes of Health (NIH) to explore the importance of these genetic interactions. The five-year grant will help Fiumera scale up the studies she is already doing in yeast. “We’re swapping mitochondrial genomes and seeing if it affects how our yeasts grow,” Fiumera says. “And we are finding that it really matters.”

Kristi Montooth, a biologist at the University of Indiana, says the work may help to illuminate why metabolic diseases are so variable and unpredictable. “There are mutations in mitochondrial genomes that, on their own, don’t have a negative effect,” she says. “But brought together with certain nuclear genomes, there’s a synergistic effect that causes them to function badly.”

The problem goes back to the evolutionary origins of the mitochondrion. Scientists believe that a mitochondrion has its own DNA because it was once a free-living bacterium that was engulfed by another cell. But instead of becoming dinner, the mitochondrion was co-opted to provide energy for its predator. The two cells managed to work together and, over time, became dependent upon one another. Mitochondria have inserted some of their genes into the nucleus, and the nucleus uses protein messengers to control how much energy the mitochondrion produces and how it does its job. It may be that the two genomes are still co-evolving and still learning the best ways to live together peacefully.

“Heather’s exploiting a lot of the genetic and genomic tools that yeast offers to take this to the next level,” says David Rand, who studies the coevolution of nuclear and mitochondrial genomes at Brown University. “The ability for Heather’s experiment to track down the interactions is going to be quite powerful.”

Yeast is a single-celled fungus with some powerful genetic tools that allow Fiumera to mix and match mitochondrial and nuclear genomes. Are there special combinations that allow better mitochondrial performance? Does “strain A” work better with mitochondrion 1 while “strain B” works better with mitochondrion 2? Fiumera will decide which combinations thrive best by subjecting her yeasts to a variety of unpleasant environments — including heat stress, oxidative stress and low-nutrient conditions — and measuring how well the mito-nuclear hybrid strains grow.

Montooth says previous studies have focused on swapping mitochondria between different species of yeast. But by looking at the variation within just one species and exploring how that variation relates to dysfunction, Fiumera’s work is more relevant for studying human disease.

So far, Fiumera’s preliminary studies have shown that the mitochondrial-nuclear interactions are responsible for as much as 20 percent of the differences in growth rates between strains. “That’s huge,” she says. Until now, Fiumera and her team have managed to look at the interactions among only a handful of strains. The NIH grant will help to buy laboratory equipment that will measure growth rates in about 200 samples at once, helping Fiumera to test hundreds of different yeast strains. She predicts they will collect more than 10,000 growth rates in just the initial phase of the project.

The second part of the experiment will be to map the genes involved in determining whether a combination is effective or ineffective. Fiumera says she’d eventually like to see whether beneficial combinations are more common in wild yeast populations; if mitochondrial-nuclear interactions are as important as biologists expect, it is likely that natural selection favors different combinations in different environments.

But Fiumera won’t be doing all of this work alone. “This project is a marriage between yeast genetics and population biology, and it is enhanced by my actual marriage to a population geneticist,” she jokes, referring to her husband, Binghamton biologist Anthony Fiumera, who will be collaborating on the project. Binghamton computer scientist Kenneth Chiu will lend his expertise to help the biologists parse through huge data sets.

Since energy production is so vital to a cell’s functioning, mitochondrial genes and machinery tend to be highly similar in organisms as far flung as yeast and humans. That allows Fiumera to hope that one day her research will be used to devise treatments for people who are suffering from debilitating metabolic disorders.

“You have to understand the mechanism behind a problem,” she says, “before you can fix the problem.”

This perspective comes from a study of ancient DNA carried out by an international research team. Rolf Quam, a Binghamton University anthropologist, was a co-author of the study led by Anders Götherström at Uppsala University and Love Dalén at the Swedish Museum of Natural History, and published in the journal Molecular Biology and Evolution.

“The Neandertals are our closest fossil relatives and abundant evidence of their lifeways and skeletal remains has been found at many sites across Europe and western Asia,” said Quam, assistant professor of anthropology. “Until modern humans arrived on the scene, it was widely thought that Europe had been populated by a relatively stable Neandertal population for hundreds of thousands of years. Our research suggests otherwise and, in light of these new results, this long-held theory now faces scrutiny.”

Focusing on mitochondrial DNA sequences from 13 Neandertal individuals, including a new sequence from the site of Valdegoba cave in northern Spain, the research team found some surprising results. When they started looking at the DNA, a clear pattern emerged. Neandertal individuals from Western Europe that were older than 50,000 years and individuals from sites in western Asia and the Middle East showed a high degree of genetic variation, on par with what might be expected from a species that had been abundant in an area for a long period of time. In fact, the amount of genetic variation was similar to what characterizes modern humans as a species. In contrast, Neandertal individuals from Western Europe that were younger than 50,000 years show an extremely reduced amount of genetic variation, less even than the present-day population of remote Iceland.

These results suggest that Western European Neandertals went through a demographic crisis, a population bottleneck that severely reduced their numbers, leaving Western Europe largely empty of humans for a period of time. The demographic crisis seems to coincide with a period of extreme cold in Western Europe. Subsequently, this region was repopulated by a small group of individuals from a surrounding area. The geographic origin of this source population is not clear, but it may be possible to pinpoint it further with additional study.

“The fact that Neandertals in Western Europe were nearly extinct, but then recovered long before they came into contact with modern humans came as a complete surprise to us,” said Dalén, associate professor at the Swedish Museum of Natural History in Stockholm. “This indicates that the Neandertals may have been more sensitive to the dramatic climate changes that took place in the last Ice Age than was previously thought.”

Quam concurs and suggests that this discovery calls for a major rethinking of the idea of cold adaptation in Neandertals.

“At the very least, this tells us that without the aid of material culture or technology, there is a limit to our biological adaptation,” Quam said. “It may very well have been the case that the European Neandertal populations were already demographically stressed when modern humans showed up on the scene.”

The results presented in the study are based entirely on degraded ancient DNA, and the analyses have therefore required advanced laboratory and computational methods. The research team includes statisticians, experts on modern DNA sequencing and paleoanthropologists from Sweden, Denmark, Spain and the United States.

“This is just the latest example of how studies of ancient DNA are providing new insights into an important and previously unknown part of Neandertal history,” Quam said. “Ancient DNA is complementary to anthropological studies focusing on the bony anatomy of the skeleton, and these kinds of results are only possible with ancient DNA studies. It’s exciting to think about what will turn up next.”

“Interdisciplinary work is of particular importance for discovery at the micro and nano scale,” he says. “This is because the properties and behaviors of small-scale structures that are building blocks of large-scale systems are typically influenced by a variety of physical forces.”

This so-called  “multi-physics phenomenon” often involves linkages among mechanical, electrical and chemical forces and opens doors to many technological possibilities.

Ke, who has developed unique ways of examining nanomaterials, brings this background to his work on DNA. He uses an atomic force microscope to observe DNA damage and repair at the molecular level.

“We are able to observe the morphology — the structure — of each individual molecule,” Ke says. “DNA is a very stable molecule, but it can experience damage. Some is from the cell and some is from radiation, mostly ultraviolet light.”

“There’s an internal strain in DNA,” he continues.  “One strand or two strands may get cut, which can mean a loss of internal strength. We observe the changes, and we can quantify how much damage the DNA experienced.”

Understanding DNA

A post-doctoral fellowship at Duke University provided Ke with an introduction to biophysics. At the time, he says, he had a high school-level understanding of DNA. These days, he can offer a brief refresher course along these lines:

DNA, or deoxyribonucleic acid, is found in every cell in the human body. Each strand contains all of a person’s hereditary information. These strands are packaged into chromosomes. One tiny variation in the DNA sequence can have dramatic results: giving someone a different eye color, for example, or putting someone at risk of developing a certain disease.

Nearly 60 years ago, scientists created the first model of the shape of DNA. And while that double helix structure — a twisted ladder — has since become famous, scientists are still teasing apart the mechanical properties of DNA.

That’s where Ke comes in.

“The mechanical property of DNA molecules is important to their biological function,” Ke says.  “We want to measure the force that stabilizes the double helix.”

He and several colleagues used atomic force microscopy to measure interactions in DNA at the single molecular level. The paper they published on the topic in Physical Review Letters in 2007 was named one of the most exciting projects in physics by the American Physical Society’s APS News.

“DNA is so important to us that any findings in this area can have a big impact,” Ke says.

Key collaborations

Ke’s DNA research is moving forward with help from two key collaborations:

With Jie (Jayne) Wu, an electrical engineer at the University of Tennessee who’s an expert in small-scale electrokinetics, he’s incorporating microfluidics into his study of DNA damage. They will use an electrical field to separate DNA based on the damage it has experienced, a method that’s potentially faster and more accurate than using an atomic force microscope to do the job.

With Binghamton mechanical engineering colleague Peter Huang, Ke is studying hybrid structures that combine DNA and carbon nanotubes. The two have a unique method of directly measuring the binding force between the DNA and the nanotube, Ke says.

While it’s difficult to separate carbon nanotubes, DNA carries a negative charge, which means individual strands repel each other. Combining them, Ke says, will make it easier to separate the carbon nanotubes.

Other researchers have demonstrated that carbon nanotubes can penetrate cell walls. If this binding interaction can interrupt the mechanical behaviors of DNA molecules so that the DNA no longer performs well — perhaps even killing the cell — it may be possible to use this technique in gene therapy.

Ke is also interested in the environmental and health impacts of these carbon nanostructures. They’re widely used in a variety of consumer products, he notes, but it’s not well understood what happens once they come into contact with human tissues.