PROFILE

Profile of Mark Stoneking PROFILE Jennifer Viegas, Science Writer

Molecular anthropologist Mark Stoneking’s contribu- tions to the field of 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 . Since then, Stoneking, now a Group Leader at the Max Planck Institute for Evolutionary An- thropology, 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 hu- man 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.

Early Interest in Biological Diversity Stoneking was born in California in 1956 but mostly grew up in Oregon, where his family spent time out- doors 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.” Mark Stoneking. Image credit: Brigitte Pakendorf As a undergraduate, Stonek- (photographer). ing gravitated to courses on and studied subjects such as human population biology and pop- were more important to the evolution of humans than ulation . He says, “Using molecular approaches were structural changes in proteins. to study evolutionary history appealed to me, the idea Hoff advised Stoneking to pursue a Master’s de- that the molecules we carry in our bodies today contain gree in genetics at his alma mater, Pennsylvania State a record of our evolutionary past, and so I decided to University. Upon earning his Bachelor of Arts in an- learn more about evolutionary genetics.” thropology in 1977, Stoneking followed Hoff’s advice Protein Variation Analysis and worked with doctorate student Bernie May in the Stoneking’s advisor, Charlie Hoff, allowed him to take laboratory of James Wright, Jr., on the evolutionary advanced graduate courses on human population ge- genetics of salmonid fishes to learn starch gel elec- netics and established a private weekly tutorial. One trophoresis of protein variation. He explains, “At that memorable discussion concerned a 1975 paper coau- time, before we had methods for analyzing DNA, an- thored by biochemists Mary-Claire King and Allan alyzing protein variation was the state-of-the-art for Wilson (2). It proposed that changes in gene regulation evolutionary genetic studies.” Their work shed light

Published under the PNAS license. This is a Profile of a member of the National Academy of Sciences to accompany the member’s Inaugural Article, e2022112118, in vol. 118, issue 1. Published February 19, 2021.

PNAS 2021 Vol. 118 No. 8 e2101332118 https://doi.org/10.1073/pnas.2101332118 | 1of3 Downloaded by guest on September 26, 2021 on genetic variation and inheritance in brook trout and Nicole Perna, they used the polymorphisms to screen other salmonid ray-finned fish (3–5). 462 individuals from Japan, Papua New Guinea, Indo- nesia, and Australia (8). The frequency of the Alu in- Envisioning the Future of Evolutionary Genetics sertion revealed significant heterogeneity among island Advances during the mid to late 1970s in restriction subgroups of the Indonesian sample and between the enzyme analysis, a method for cleaving DNA at specific Japanese–Indonesian and Australian–New Guinean sites, facilitated the creation of mitochondrial DNA populations. (mtDNA) maps of several species, including Homo sa- piens. Stoneking saw the potential of mtDNA research. Forensic Applications of mtDNA “It seemed to me that was where the future of evolu- Stoneking’s work with geneticist Henry Erlich at the tionary genetics was headed, so I was determined to go Cetus Corporation, where the PCR was invented, in- to a lab where I could learn about mtDNA,” he says. troduced him to the forensic DNA community. He After earning a Master’s degree in 1979, Stoneking maintained these ties while at Pennsylvania State Uni- attended University of California, Berkeley for his doc- versity and helped the Federal Bureau of Investigation torate in genetics. His advisor was Wilson, who was (FBI) and the US Armed Forces DNA Identification juggling multiple projects involving mtDNA variation. Laboratory to establish mtDNA laboratories. He says, Stoneking chose to work with University of California, “We also did some casework, which in turn got us in- Berkeley postdoctorate Rebecca Cann. Since the late volved in some historical identifications.” 1970s, Cann had been collecting human mtDNA sam- Two of the most notable projects involved mtDNA ples from various parts of the world. The experience, studies of remains purported to respectively belong to including Wilson’s mentoring, led to Stoneking’s deci- the American outlaw Jesse James and to the Russian sion to become a molecular anthropologist. Grand Duchess Anastasia Romanova. Stoneking and colleagues’ mtDNA analysis of remains exhumed in Discovery of “” Kearney, Nebraska, suggested that they belonged to Stoneking contributed research on placental tissue James (9). Genetic analysis of a hair sample suppos- samples from and New Guineans edly from Anna Anderson Manahan, who claimed to to Cann’s project. In total, Wilson, Cann, and Stoneking be Romanova, revealed that her assertions were false retrieved mtDNA from 147 individuals drawn from five (10). For these and other investigations, in 1998 geographic populations. Analysis of the compiled data Stoneking received the FBI Award for Service to the were presented in a seminal 1987 Nature paper pub- Forensic DNA Community. lished shortly after Stoneking earned his doctoral de- gree and while he was a University of California, Historical Demographies, Origin of Clothing Berkeley postdoctoral associate (6). The following year, Stoneking assumed his present The paper was the first to propose a recent African position at the Max Planck Institute and became an origin of modern humans. All of the mtDNA samples honorary professor of biological anthropology at the were shown to stem from a woman postulated to have University of Leipzig. He has continued to maintain an lived in ∼200,000 years ago. Hematologist James active research program. Wainscoat dubbed her “Mitochondrial Eve” in an ac- In 2001, Stoneking and his team correlated human companying commentary (7). Concerning the findings, mtDNA and Y chromosome variation with residence which received extensive media coverage and sparked patterns, demonstrating the effect that matrilocal and years of heated debates, Stoneking says: “It was an patrilocal residence can have on their members’ ge- extraordinary experience, from the laboratory work, to nomes (11). Another comparison of Y chromosome and the data analysis, and then the public reception. No- mtDNA variation from 51 globally distributed pop- body else had attempted to construct phylogenetic ulations showed that human populations were larger trees from a dataset of this size.” before the out-of-Africa modern human migration (12). After reading a “fun facts about lice” flyer that his New Marker for Human Population Studies eldest son brought home from school, Stoneking was After a year as a staff scientist at Lawrence Berkeley inspired to use a molecular clock approach to date the Laboratory’s Human Center, followed by divergence of head and body lice. He theorized that a year as an associate research scientist at California- the divergence must have coincided with the origin of based Cetus Corporation, in 1990 Stoneking accepted clothing, providing a new ecological niche. The a position as an assistant professor in the Department of resulting article concludes that this divergence hap- Anthropology at Pennsylvania State University, where pened 72,000 years ago, which corresponds with the he advanced to associate professor and then a full expansion of modern humans out of Africa (13). professorship. In 1990 Stoneking attended a conference during Introgression from Archaic to Modern Humans which geneticists Mark Batzer and Prescott Deininger Stoneking’s research often involves both collection of gave a talk about new types of DNA sequence variants human DNA samples and collaborations with local they had identified: Alu insertion polymorphisms. scientists to expand such field work. Codirecting an Stoneking realized the polymorphisms had useful prop- international team, for example, Stoneking quantified erties for evolutionary genetic studies, and the three be- Denisovan admixture in 33 populations from Asia and gan a collaboration. In 1992, with undergraduate student Oceania (14). The data, together with that of prior

2of3 | PNAS Viegas https://doi.org/10.1073/pnas.2101332118 Profile of Mark Stoneking Downloaded by guest on September 26, 2021 studies, suggests Denisovan ancestry was restricted to theorize that human health may be affected by the populations east of the transitional zone between Asia functional consequences of these somatic mutations. and Australia. Stoneking and colleagues leveraged the information to infer that there were at least two mi- Settlement of the Mariana Islands, Polynesia grations of modern humans to East Asia and the Pacific, Stoneking’s Inaugural Article (1) provides new insights with the admixture likely having occurred in Indonesia. on how the Mariana Islands and Polynesia were first Collaborating with computational biologist Murray settled. With the help of coauthor and ancient DNA Cox, Stoneking and another international team showed specialist Matthias Meyer, Stoneking and colleagues that there were multiple events of Denisovan-related obtained DNA from two skeletons from the Ritidian Beach admixture in Papuans (15). The findings suggest that Cave site in northern Guam, dating to ∼2,200 years ago. the sister hominin group to Neanderthals may have The genetic analysis links the skeletons’ ancestry to the been present in New Guinea and therefore could have Philippines and suggests that the first colonists of the been capable of crossing massive water barriers. Marianas and of Polynesia stem from a common ancestral group. Saliva Microbiome, Heteroplasmy In June 2022, Stoneking plans to retire and move When Stoneking and his colleagues switched from to Lyon, France, where his wife Brigitte Pakendorf is a performing cheek swabs to collecting saliva samples senior scientist at a Centre National de la Recherche during field work, they gained a new resource: the Scientifique linguistics laboratory. He is currently fo- bacterial DNA present in saliva. This prompted them cusing on finishing projects concerning Southeast Asia to carry out the first survey of global diversity in the and Oceania, with some involving ancient DNA and human saliva microbiome (16). The research deter- others involving modern human populations. He mined that the major factor influencing bacterial di- hopes that the genetic history of the entire Southeast versity was distance from the equator. The findings Asia region will soon be documented. He also antici- hold potential for future studies on human population pates updating An Introduction to Molecular Anthro- history and how the saliva microbiome affects human pology (18), Stoneking’s well-regarded book on health. human genetic history. Over the past decade, Stoneking and his team Stoneking also plans to join the Centre National de have switched to next-generation sequencing of la Recherche Scientifique Biometry and Evolutionary complete mtDNA , which allows them to Biology Laboratory next year. With retirement from analyze variation within individuals, a phenomenon the Max Planck Institute looming, he expresses grati- called heteroplasmy. They conducted the first large- tude for his team and collaborators. Stoneking also scale study of how heteroplasmy varies across the says, “What has made all of this work possible is the entire human mtDNA genome and showed that there , which has the vision of identifying is positive selection for specific alleles at specific nu- scientists who can do good work and giving them cleotide sites in specific tissues (17). The authors what they need to carry out the research.”

1 I. Pugach et al., Ancient DNA from Guam and the peopling of the Pacific. Proc. Natl. Acad. Sci. U.S.A. 118, e2022112118 (2021). 2 M.-C. King, A. C. Wilson, Evolution at two levels in humans and . Science 188, 107–116 (1975). 3 B. May, M. Stoneking, J. E. Wright, Joint segregation of malate dehydrogenase and diaphorase loci in brown trout (Salmo trutta). Trans. Am. Fish. Soc. 108, 373–377 (1979). 4 B. May, J. E. Wright, M. Stoneking, Joint segregation of biochemical loci in Salmonidae: Results from experiments with Salvelinus and review of the literature on other species. J. Fish. Res. Board Can. 36, 1114–1128 (1979). 5 M. Stoneking, B. May, J. E. Wright Jr, Genetic variation, inheritance, and quaternary structure of malic enzyme in brook trout (Salvelinus fontinalis). Biochem. Genet. 17, 599–619 (1979). 6 R. L. Cann, M. Stoneking, A. C. Wilson, Mitochondrial DNA and . Nature 325,31–36 (1987). 7 J. Wainscoat, Human evolution. Out of the garden of Eden. Nature 325, 13 (1987). 8 N. T. Perna, M. A. Batzer, P. L. Deininger, M. Stoneking, Alu insertion polymorphism: A new type of marker for human population studies. Hum. Biol. 64, 641–648 (1992). 9 A. C. Stone, J. E. Starrs, M. Stoneking, Mitochondrial DNA analysis of the presumptive remains of Jesse James. J. Forensic Sci. 46, 173–176 (2001). 10 P. Gill et al., Establishing the identity of Anna Anderson Manahan. Nat. Genet. 9,9–10 (1995). 11 H. Oota, W. Settheetham-Ishida, D. Tiwawech, T. Ishida, M. Stoneking, Human mtDNA and Y-chromosome variation is correlated with matrilocal versus patrilocal residence. Nat. Genet. 29,20–21 (2001). 12 S. Lippold et al., Human paternal and maternal demographic histories: Insights from high-resolution Y chromosome and mtDNA sequences. Investig. Genet. 5, 13 (2014). 13 R. Kittler, M. Kayser, M. Stoneking, Molecular evolution of Pediculus humanus and the origin of clothing. Curr. Biol. 13 ,1414–1417 (2003). 14 D. Reich et al., Denisova admixture and the first modern human dispersals into Southeast Asia and Oceania. Am. J. Hum. Genet. 89, 516–528 (2011). 15 G. S. Jacobs et al., Multiple deeply divergent Denisovan ancestries in Papuans. Cell 177, 1010–1021.e32 (2019). 16 I. Nasidze, J. Li, D. Quinque, K. Tang, M. Stoneking, Global diversity in the human salivary microbiome. Genome Res. 19, 636–643 (2009). 17 M. Li, R. Schröder, S. Ni, B. Madea, M. Stoneking, Extensive tissue-related and allele-related mtDNA heteroplasmy suggests positive selection for somatic mutations. Proc. Natl. Acad. Sci. U.S.A. 112, 2491–2496 (2015). 18 M. Stoneking, An Introduction to Molecular Anthropology (Wiley-Blackwell, New Jersey, 2016).

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