Profile of Mark Stoneking

Molecular anthropologist Mark Stoneking’s contributions to the field of human evolution began in the mid-1980s. As a graduate student at the University of California, Berkeley, Stoneking helped to identify the first genetic evidence supporting the African origin of modern humans. Since then, Stoneking, now a Group Leader at the Max Planck Institute for Evolutionary Anthropology, has used innovative genetic methods to investigate human migrations, demographic histories, genetic introgression from archaic to modern humans, human cultural practices, and more. For his Inaugural Article (1), Stoneking, who was elected to the National Academy of Sciences in 2020, analyzed DNA from human skeletons found at a 2,200-year-old site in Guam. The findings of Stoneking and his colleagues suggest that Guam’s first colonists originated in the Philippines from an ancestral group linked to the Mariana Islands and Polynesia.

Mark Stoneking. Image credit: Brigitte Pakendorf (photographer).

Early Interest in Biological Diversity

Stoneking was born in California in 1956 but mostly grew up in Oregon, where his family spent time outdoors camping and fishing. He says, “Oregon is a wonderfully diverse environment to grow up in—from where we lived, in Eugene, we could be at the coast or up in the Cascade Mountains in an hour—so I grew up with an appreciation for, and interest in, the diversity of the environment, especially the biological diversity.”

As a University of Oregon undergraduate, Stoneking gravitated to courses on anthropology and studied subjects such as human population biology and population genetics. He says, “Using molecular approaches to study evolutionary history appealed to me, the idea that the molecules we carry in our bodies today contain a record of our evolutionary past, and so I decided to learn more about evolutionary genetics.”

Protein Variation Analysis

Stoneking’s advisor, Charlie Hoff, allowed him to take advanced graduate courses on human population genetics and established a private weekly tutorial. One memorable discussion concerned a 1975 paper coauthored by biochemists Mary-Claire King and Allan Wilson (2). It proposed that changes in gene regulation were more important to the evolution of humans than were structural changes in proteins.

Hoff advised Stoneking to pursue a Master’s degree in genetics at his alma mater, Pennsylvania State University. Upon earning his Bachelor of Arts in anthropology in 1977, Stoneking followed Hoff’s advice and worked with doctorate student Bernie May in the laboratory of James Wright, Jr., on the evolutionary genetics of salmonid fishes to learn starch gel electrophoresis of protein variation. He explains, “At that time, before we had methods for analyzing DNA, analyzing protein variation was the state-of-the-art for evolutionary genetic studies.” Their work shed light on genetic variation and inheritance in brook trout and other salmonid ray-finned fish (3–5).

Envisioning the Future of Evolutionary Genetics

Advances during the mid to late 1970s in restriction enzyme analysis, a method for cleaving DNA at specific sites, facilitated the creation of mitochondrial DNA (mtDNA) maps of several species, including Homo sapiens. Stoneking saw the potential of mtDNA research. “It seemed to me that was where the future of evolutionary genetics was headed, so I was determined to go to a lab where I could learn about mtDNA,” he says.

After earning a Master’s degree in 1979, Stoneking attended University of California, Berkeley for his doctorate in genetics. His advisor was Wilson, who was juggling multiple projects involving mtDNA variation. Stoneking chose to work with University of California, Berkeley postdoctorate Rebecca Cann. Since the late 1970s, Cann had been collecting human mtDNA samples from various parts of the world. The experience, including Wilson’s mentoring, led to Stoneking’s decision to become a molecular anthropologist.

Discovery of “Mitochondrial Eve”

Stoneking contributed research on placental tissue samples from aboriginal Australians and New Guineans to Cann’s project. In total, Wilson, Cann, and Stoneking retrieved mtDNA from 147 individuals drawn from five geographic populations. Analysis of the compiled data were presented in a seminal 1987 Nature paper published shortly after Stoneking earned his doctoral degree and while he was a University of California, Berkeley postdoctoral associate (6).

The paper was the first to propose a recent African origin of modern humans. All of the mtDNA samples were shown to stem from a woman postulated to have lived in Africa ∼200,000 years ago. Hematologist James Wainscoat dubbed her “Mitochondrial Eve” in an accompanying commentary (7). Concerning the findings, which received extensive media coverage and sparked years of heated debates, Stoneking says: “It was an extraordinary experience, from the laboratory work, to the data analysis, and then the public reception. Nobody else had attempted to construct phylogenetic trees from a dataset of this size.”

New Marker for Human Population Studies

After a year as a staff scientist at Lawrence Berkeley Laboratory’s Human Genome Center, followed by a year as an associate research scientist at California-based Cetus Corporation, in 1990 Stoneking accepted a position as an assistant professor in the Department of Anthropology at Pennsylvania State University, where he advanced to associate professor and then a full professorship.

In 1990 Stoneking attended a conference during which geneticists Mark Batzer and Prescott Deininger gave a talk about new types of DNA sequence variants they had identified: Alu insertion polymorphisms. Stoneking realized the polymorphisms had useful properties for evolutionary genetic studies, and the three began a collaboration. In 1992, with undergraduate student Nicole Perna, they used the polymorphisms to screen 462 individuals from Japan, Papua New Guinea, Indonesia, and Australia (8). The frequency of the Alu insertion revealed significant heterogeneity among island subgroups of the Indonesian sample and between the Japanese–Indonesian and Australian–New Guinean populations.

Forensic Applications of mtDNA

Stoneking’s work with geneticist Henry Erlich at the Cetus Corporation, where the PCR was invented, introduced him to the forensic DNA community. He maintained these ties while at Pennsylvania State University and helped the Federal Bureau of Investigation (FBI) and the US Armed Forces DNA Identification Laboratory to establish mtDNA laboratories. He says, “We also did some casework, which in turn got us involved in some historical identifications.”

Two of the most notable projects involved mtDNA studies of remains purported to respectively belong to the American outlaw Jesse James and to the Russian Grand Duchess Anastasia Romanova. Stoneking and colleagues’ mtDNA analysis of remains exhumed in Kearney, Nebraska, suggested that they belonged to James (9). Genetic analysis of a hair sample supposedly from Anna Anderson Manahan, who claimed to be Romanova, revealed that her assertions were false (10). For these and other investigations, in 1998 Stoneking received the FBI Award for Service to the Forensic DNA Community.

Historical Demographies, Origin of Clothing

The following year, Stoneking assumed his present position at the Max Planck Institute and became an honorary professor of biological anthropology at the University of Leipzig. He has continued to maintain an active research program.

In 2001, Stoneking and his team correlated human mtDNA and Y chromosome variation with residence patterns, demonstrating the effect that matrilocal and patrilocal residence can have on their members’ genomes (11). Another comparison of Y chromosome and mtDNA variation from 51 globally distributed populations showed that human populations were larger before the out-of-Africa modern human migration (12).

After reading a “fun facts about lice” flyer that his eldest son brought home from school, Stoneking was inspired to use a molecular clock approach to date the divergence of head and body lice. He theorized that the divergence must have coincided with the origin of clothing, providing a new louse ecological niche. The resulting article concludes that this divergence happened 72,000 years ago, which corresponds with the expansion of modern humans out of Africa (13).

Introgression from Archaic to Modern Humans

Stoneking’s research often involves both collection of human DNA samples and collaborations with local scientists to expand such field work. Codirecting an international team, for example, Stoneking quantified Denisovan admixture in 33 populations from Asia and Oceania (14). The data, together with that of prior studies, suggests Denisovan ancestry was restricted to populations east of the transitional zone between Asia and Australia. Stoneking and colleagues leveraged the information to infer that there were at least two migrations of modern humans to East Asia and the Pacific, with the admixture likely having occurred in Indonesia.

Collaborating with computational biologist Murray Cox, Stoneking and another international team showed that there were multiple events of Denisovan-related admixture in Papuans (15). The findings suggest that the sister hominin group to Neanderthals may have been present in New Guinea and therefore could have been capable of crossing massive water barriers.

Saliva Microbiome, Heteroplasmy

When Stoneking and his colleagues switched from performing cheek swabs to collecting saliva samples during field work, they gained a new resource: the bacterial DNA present in saliva. This prompted them to carry out the first survey of global diversity in the human saliva microbiome (16). The research determined that the major factor influencing bacterial diversity was distance from the equator. The findings hold potential for future studies on human population history and how the saliva microbiome affects human health.

Over the past decade, Stoneking and his team have switched to next-generation sequencing of complete mtDNA genomes, which allows them to analyze variation within individuals, a phenomenon called heteroplasmy. They conducted the first large-scale study of how heteroplasmy varies across the entire human mtDNA genome and showed that there is positive selection for specific alleles at specific nucleotide sites in specific tissues (17). The authors theorize that human health may be affected by the functional consequences of these somatic mutations.

Settlement of the Mariana Islands, Polynesia

Stoneking's Inaugural Article (1) provides new insights on how the Mariana Islands and Polynesia were first settled. With the help of coauthor and ancient DNA specialist Matthias Meyer, Stoneking and colleagues obtained DNA from two skeletons from the Ritidian Beach Cave site in northern Guam, dating to ∼2,200 years ago. The genetic analysis links the skeletons’ ancestry to the Philippines and suggests that the first colonists of the Marianas and of Polynesia stem from a common ancestral group.

In June 2022, Stoneking plans to retire and move to Lyon, France, where his wife Brigitte Pakendorf is a senior scientist at a Centre National de la Recherche Scientifique linguistics laboratory. He is currently focusing on finishing projects concerning Southeast Asia and Oceania, with some involving ancient DNA and others involving modern human populations. He hopes that the genetic history of the entire Southeast Asia region will soon be documented. He also anticipates updating An Introduction to Molecular Anthropology (18), Stoneking’s well-regarded book on human genetic history.

Stoneking also plans to join the Centre National de la Recherche Scientifique Biometry and Evolutionary Biology Laboratory next year. With retirement from the Max Planck Institute looming, he expresses gratitude for his team and collaborators. Stoneking also says, “What has made all of this work possible is the Max Planck Society, which has the vision of identifying scientists who can do good work and giving them what they need to carry out the research.”