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Krishna Veeramah

Above, Shyamalika Gopalan. The image on the screen shows methylation levels with age. Photo by Casey Youngflesh

By Daniel Dunaief

The Museum of Natural History in New York City features a slice of a 1,400-year-old sequoia tree that was cut down in California in 1891. The cross section of the tree offers a testament to history on its inside. That’s where the tree rings that grow every year mark the passing of another year. As it turns out, humans have something in common with trees. While people may not have rings in bones that an observer can see, they do have age-related changes in their genetic material, or DNA.

Human genes go through a process called methylation in which a methyl group comprised of a carbon and three hydrogens attaches to DNA. Methylation upstream of a gene generally reduces transcription, or the copying of that gene into messenger RNA that can then begin the process of building proteins.

Shyamalika Gopalan demonstrates how she prepares to extract DNA. Photo by Casey Youngflesh

Using broad time-based methylation changes, Shyamalika Gopalan, who is earning her doctorate at Stony Brook University in the Department of Ecology and Evolution, recently received a three-year grant from the Department of Justice to refine an understanding of methylation and aging. The DOJ would like to use this kind of analysis to gather more information from a scene at which the remaining clues include DNA that isn’t in one of its databases.

Gopalan isn’t the first scientist to study genetic methylation and aging. Other scientists have used blood, saliva and other tissues. She is starting with one type of tissue in the bone. “I’m trying to make” the analysis “more specific to bones,” she said. She doesn’t know how much variation she will find in the age-related methylation patterns depending on ethnicity and lifestyle. “It does appear that some sites are remarkably ‘clock-like,’” she said. “It is these types of sites I’m hoping to find and use in my research.”

Gopalan explained that millions of sites can be methylated. She’s hoping to hone in on those that act more like a clock and that change in a linear manner with time. She’s not sure how many sites she’ll use and said some changes in methylation involve removing methyl groups. “Some methylation increases and some decreases,” she said. “If you know the pattern with age at any site, you can start to build an estimate from those.”

Methylation occurs with age for several possible reasons. “A major theory for these changes in methylation level with age is that the epigenetic patterns are drifting from the optimum,” she said. “This may explain some, or even most, of the changes we observe, but I don’t think it is universally true for all sites in the genome.” Still, there probably is a biologically relevant reason why some of these sites are changing, she suggested.

Gopalan said we know that these methylation patterns are crucial in early development, from conception to birth and she suggested it probably doesn’t completely stop changing there. Some sites are probably regulated throughout life.

Gopalan is hoping to have the bone data prepared by this summer and then believes she’ll be able to get methylation types and start working on a computer algorithm to build a predictor for the next year. After her initial work, she will also shift to saliva and blood.

Like a scene from “Law & Order” or other crime shows, the DNA methylation test may be another clue for police officers or prosecutors to use to rule in or out potential suspects from a crime scene where DNA, but not a driver’s license, is left behind. If the genetic material is not in a database, “you could build a profile and it could be useful for narrowing down suspects,” Gopalan said. At this point, she is taking data for people of age classes but with different ethnicities and lifestyles and comparing them to people of a different age with a similar range of backgrounds and lifestyles.

Gopalan is using samples from medical schools around the New York area, borrowing from anatomy departments where people have donated their bodies to research or teaching. More broadly, she is interested in studying diverse populations, especially in Africa. She has worked with her thesis advisor Brenna Henn, exploring methylation from two different populations. These are the ‡Khomani San of South Africa and the Baka of Cameroon.

Gopalan was interested in working with methylation as a biomarker for aging when she came across this funding opportunity from the DOJ. “It was a good fit for what I had already been studying,” she said, adding that she hopes this method will be used in the future in forensics to assist in criminal investigations.

Krishna Veeramah, an assistant professor of primate genomics at Stony Brook and the chair of her thesis committee, described Gopalan as an “intellectually engaged student who is always eager to absorb information.” Veeramah explained in an email that he thinks “there is scope for this work to transition from basic research” to an application “in criminal forensics and related areas. It will certainly require more work and testing.”

Gopalan has been at SBU for over three years. She lives in Crown Heights, Brooklyn, and commutes about 90 minutes each way most days. She enjoys the beaches, farms, apple picking and the natural beauty of the area. Gopalan would like to continue to perform research after she earns her doctorate, whether that’s with a company, a research institution or with a university. She is excited about extracting and working with DNA, particularly from archeological sites. These samples “come from a field and, once you dust them off, it makes it personal. This is a part of a story.”

Krishna Veeramah. Photo by Dean Bobo

By Daniel Dunaief

People have left all kinds of signs about their lives from hundreds and even thousands of years ago. In addition to artifacts that provide raw material for archeologists, anthropologists and historians, they also left something modern science can explore: their genes.

Genetic information locked inside their bones can add to the dialogue by providing details about what regions people might have come from and when they arrived. A group that includes Krishna Veeramah, an assistant professor of primate genomics at Stony Brook University, is using genetic information, combined with archeological evidence, to gain a better understanding of the events in Europe immediately after the fall of the Roman Empire, between the fifth and sixth centuries.

“We want to test questions that integrate historical and biological information,” said Veeramah, who is working with a multinational team of scientists. “We want to integrate archeological information.”

This is a time period in which there is some disagreement among historians about what happened after the fall of the Roman Empire. Patrick Geary, the principal investigator on a project that traces early medieval population movements through genomic research, said that this period fundamentally changed not only the demographic makeup of the populations but also the social and political constellation of Europe. These scientists are hoping to contribute their analysis of the genetic material of 1,200 people from several cemeteries to a discussion of the history of the continent.

So, how does this work? Paleogenomic data offers information from hundreds of thousands to millions of positions along the genome, which are called markers or single-nucleotide polymorphisms. Looking at the markers in total, researchers can identify small but systematic genetic differences between groups. They hope to determine where an individual’s ancestors are from based on the bones they are studying. They can only come to these conclusions, Veeramah explained, once they have sampled large numbers of people from different geographic areas during that time period. The genetic differences he is seeing are extremely small. He uses enormous pools of data that can allow him to explore subtle patterns, which emerge at the group level.

While the notion of using the genetic code to contribute information to discussions about the movement of groups of people has its proponents and practitioners, Geary and Veeramah recognize the skepticism, alarm and misdirection that comes from exploring subtle genetic differences among various groups of people. “The application of genetics to the human past is dark,” Geary said, pointing to eugenics discussions. “That’s understandable. We are emphatically opposed to such previous misuses of genetic research.” Some scientists, Geary said, are also suggesting that genetic studies will replace manuscripts or other clues. “We need all types of information,” Geary said.

Indeed, in a cemetery in Hungary that contained about 45 graves, Veeramah is studying genetic differences between two graves that are oriented in another direction from the other adult-sized graves. These two graves don’t contain any grave goods and appear to have different construction. The initial genomic analysis of a subset of individuals suggest they have a genetic profile that is different from other members of the cemetery and may show more of a connection to modern people from southern Europe rather than northern and central Europe, like the rest of the samples. The way these two graves were arranged offers intriguing possibilities, Veeramah said. This may suggest that these individuals had a distinct biological identity, which could impact some aspects of their social identity. To reach any conclusions, he hopes to collect more data from more individuals.

Geary suggested the kind of work he and Veeramah are doing, along with partners in other countries, will offer insight into the different paths of men and women. When paleogenomics first arrived as a discipline, historians were slow to embrace it. At the 2008 American Historical Association’s annual meeting, Geary gave a talk at which about 10 people attended. In January, at the 2017 American Historical Association meeting in Denver, Veeramah will discuss how a study of the Lombards offers a framework for integrating history, archeology and genomics. The president of the American Historical Association invited Veeramah and has publicized the talk as a presidential panel.

“I do believe that paleogenomics has become an important aspect of archeological work, and that the newly developed procedures for sequencing and analyzing genetic material adds a whole new dimension to work on archeological sites,” Patrick Manning, the president of the AHA and a professor of world history at the University of Pittsburgh, wrote in an email. Veeramah’s “work on the Lombards addresses an important issue in the Germanic migrations throughout Europe, long debated and now with important new information.”

Veeramah arrived at Stony Brook University in 2014 and lives in Sound Beach. He grew up outside London in Dartford and attended the same secondary school as Mick Jagger. While he likes some of the Rolling Stones songs, he’s more of a Dizzee Rascal fan. Veeramah plans to have a lab installed by next summer, when he hopes to analyze bones from archeological sites shipped from Europe.

In the meantime, he will continue to analyze genetic information coming from partners in Europe. While Veeramah and others in the field have published papers in prestigious journals like the Proceedings of the National Academy of Sciences and Science, they have struggled to receive funding from American funding agencies at the same level as their European counterparts.

“It is somewhat surprising how far behind the U.S. has gotten in this area,” Veeramah said. European grants can be more adaptable and can put more value on multidisciplinary work. “This is a systematic issue for U.S. funding. I hope it will be addressed soon.”