Sarah Tishkoff

Sarah Anne Tishkoff (born December 26, 1965) is an American geneticist and the David and Lyn Silfen Professor in the Department of Genetics and Biology at the University of Pennsylvania. She also serves as a director for the American Society of Human Genetics and is an associate editor at PLOS Genetics, G3 (Genes, Genomes, and Genetics), and Genome Research. She is also a member of the scientific advisory board at the David and Lucile Packard Foundation.

Tishkoff has been a leading figure in using genetics to advance understanding of modern human diversity. In particular she has made significant contributions to research on human genetic variation in African populations. In 1996, she and colleagues published the first paper to support the Out-of-Africa hypothesis using the nuclear genome, illustrating the extent of diversity among African populations. In 2001, Tishkoff and colleagues were some of the first to show the genomic signature of natural selection in human populations. Her more recent work includes the largest genomic study across ethnically diverse Africans, and the identification of novel genetic variants associated with skin color.

Tishkoff is a recipient of a National Institutes of Health Director's Pioneer Award, a David and Lucile Packard Career Award, a Burroughs/Wellcome Fund Career Award, and a Penn Integrates Knowledge (PIK) endowed chair.

Early life Sarah Tishkoff was born on December 26, 1965, in Los Angeles, California. She moved from Los Angeles to East Lansing, Michigan, when she was five, and from East Lansing to Klamath Falls, Oregon, in her early teens. Her parents were both involved in academia. Her father was a professor of hematology and oncology at the University of California, Los Angeles and later the Director of the Red Cross for the Midwest of the United States.

Tishkoff's career was significantly influenced by several mentors throughout her education. While at UC Berkeley, she took courses in linguistics, cultural anthropology, physical anthropology, and archaeology, among other subjects. Tishkoff and her lab members study evolutionary genomics, African phenotypic diversity, the genetic basis of resistance to infectious diseases, and the genetic basis of human adaptations. Their work combines field work, laboratory research, and computational approaches to examine the effect of genetic variation in living and past African populations.

In 2017, Tishkoff was elected to the National Academy of Sciences, which is considered a high honor that recognizes distinguished scientists in their respective fields. Throughout her career, Tishkoff has also been a part of numerous professional associations and scientific societies. She currently serves on the board of director for the American Society of Human Genetics, and she is a member of the scientific advisory board at the David and Lucile Packard Foundation. She is an associate editor at PLOS Genetics, G3 (Genes, Genomes, and Genetics), and Genome Research.

Research The primary focus of Tishkoff's research career has been on human genetic variation in African populations. The central aims of her research are to better understand the origins of modern humans and the histories of African populations, and the genetic underpinnings of disease susceptibility. Advances in these areas of research may aid drug development for diseases with known genetic bases, and the development of more effective medical treatments for living African populations.

African genomics

Integrative genomics Tishkoff's research methodology applies an integrative genomics approach that combines data from the genome, epigenome, proteome, transcriptome, metabolome, and microbiome of various African ethnic groups to identify genetic and environmental factors that affect traits related to human measurements, metabolism and immune system.

Evolutionary genomics Tishkoff's work also addresses questions about the evolutionary history of Homo sapiens. One of the key findings in this area of research includes the discovery of genetic signatures of interbreeding between anatomically modern humans and extinct hominins. Tishkoff was also involved in a study that rejected the hypothesis that ancestors of anatomically modern humans were genetically isolated in Africa. This study was based on whole-genome simulations from two Western African Pygmy populations, Biaka and Baka, and suggested the existence of introgression from an unknown archaic population.

Phenotypic diversity Sarah Tishkoff and colleagues also focus their research on acquiring genomic and phenotypic data from geographically and culturally distinct African populations, which are underrepresented in genetic studies and whose analysis may uncover new aspects of human evolutionary history, including susceptibility to diseases and migration patterns. By genotyping approximately 2400 individuals from 121 geographically diverse African populations, Tishkoff and colleagues found evidence for 14 genetically divergent ancestral populations in Africa, and by comparing the genetic information with archaeological and self-described phenotypic data they showed high cultural and linguistic similarity within each cluster. Using their novel set of acquired genetic markers they were also able to trace back the shared ancestry of African Americans with African populations, finding a dominant shared ancestry from Niger-Kordofanian populations in Western Africa. Their work has demonstrated the need for further genomic analyses of African populations as a means of identifying correlations between allele frequencies and risk of certain diseases, and potentially designing therapeutic drugs for treating diseases in populations with similar genetic backgrounds. Haplotype analysis of Med and A- allele mutations at the G6PD locus revealed that their increased frequency occurred after the agricultural practices began. They also found several alleles at the locus that were found ubiquitously in malarial regions, and one of them, "ICAM-1Kilifi," was present in high frequencies in Asian and African populations. Two coding variants, G1 and G2, for the APOL1 protein are associated with resistance to African trypanosomiasis, or African sleeping sickness, but they also increase the risk of chronic kidney diseases. These mutations are an example of convergent evolution due to the shared cultural selective pressures of animal domestication and milk consumption, and they are a clear case of gene-culture coevolution.

High altitude adaptations in Ethiopians In 2012, Tishkoff participated in a study published in Genome Biology that compared the hemoglobin levels between populations living at high and low altitudes in Ethiopia. The study found that there are statistically significant differences in the hemoglobin levels between the high altitude population, the Amhara people, and the low altitude population, the Aari and Hamar people. The genomic analysis recovered different gene candidates underlying adaptation to high altitude (CBARA1, VAV3, ARNT2, and THRB) TAS2R38 is hypothesized to underlie a dietary adaptation that allows for avoidance of bitter-tasting poisonous foods. Tishkoff and colleagues hypothesized that African populations with different diets would have differences in their receptor genes due to selection associated with their diets. The study was based on a sample of 57 African populations consisting of 611 individuals and a comparative set of 132 non-Africans from the Middle East, Asia, and the Americas. Researchers measured participants' PTC bitter taste sensitivity using a modified version of the Harris - Kalmus threshold method, sequenced genomes, and completed haplotype and genotype–phenotype association analyses. Results failed to support the original hypothesis. African populations with divergent diets showed similar haplotype frequencies and there was little genetic differentiation between Africans and non-Africans. Results suggested that the short stature in Western African Pygmies may have resulted from selection for early reproduction, and metabolic and immune functions and that there may have been several selective events at different times in pygmy evolution. Similarly, Tishkoff has released a short series of research talks on African Genomics with the organization iBiology, whose mission is to "convey, in the form of open-access free videos, the excitement of modern biology and the process by which scientific discoveries are made". Other notable examples are her videos on The Evolution of Human Biodiversity: Local Adaptation, Adaptation to Taste and Lactose Intolerance in Africa, and Evolution and Adaptation in Africa: Implications for Health and Disease.

Awards, honors, and memberships As an undergraduate at University of California, Berkeley, Tishkoff received the UC Berkeley President's Undergraduate Fellowship in 1987 and graduated with University high honors and honors in anthropology. Her work would go on to be acknowledged by the David and Lucile Packard Fellowship for Science and Engineering in 2001.

While serving on the faculty at University of Maryland's College of Life Sciences, Tishkoff received the Junior Faculty Excellence Award in 2003. In 2009, Tishkoff was awarded the National Institutes of Health Director's Pioneer Award to fund her research in Africa detailing genetic and environmental factors that influence human physiological traits. She was elected to the National Academy of Sciences in 2017, and is also on the board of directors for the American Society of Human Genetics (ASHG).