Luigi Luca Cavalli-Sforza. 25 January 1922—31 August 2018

Though it was as a bacteriologist that Luca Cavalli-Sforza first flourished scientifically, it was the subject of human population genetics that he dominated for the second half of the twentieth century. He pioneered both genetical demography and the construction of the genetical evolutionary tree of man, initially from gene-frequency data and ultimately from tracing the paths of descent of individual DNA sequences. He was among the first to apply the new computers to the problems he encountered, using his self-taught knowledge of mathematics and statistics. He conducted expeditions to the Pygmies of the African rainforest and studied the spread of agriculture in Europe, demonstrating the similarity between its wave of advance and the contours of population gene frequency. He noted the correspondence between the descent tree of languages and the human evolutionary tree. Cavalli headed university departments in Pavia and then Stanford, surrounding himself with young colleagues and driving forward research with vigorous discussion and unceasing enthusiasm. His knowledge was spread across medicine and genetics, anthropology and linguistics, archaeology and history, and he expressed himself fluently in speech and writing in Italian, English and French. A true Renaissance man. His published work in human population genetics and cultural evolution over more than 50 years constituted ‘one long argument’, as Darwin said of The origin of species . The villages of the Parma valley were his Galapagos Islands, and random genetic drift his adjunct to natural selection for the case of man. His demonstration of the importance of drift in recent human evolution informed the model for constructing evolutionary trees from gene-frequency data. On this one long argument he wrote and lectured ceaselessly, not only for other scientists but also for a wider audience, always mindful of a responsibility to promote an understanding of man's biology and evolutionary history for society's benefit. In so doing he brought an informed and rational approach to the problem of human diversity and the problems of human diversity.

Race, Ethnicity, Ancestry, and Genomics in Hawai‘i

This paper examines how populations in a multiethnic cohort project used to study environmental causes of cancer in Hawai‘i have been reorganized in ways that have contributed to the racialization of the human genome. We examine the development of two central genomic data infrastructures, the multiethnic cohort (MEC) and a collection of reference DNA called the HapMap. The MEC study populations were initially designed to examine differences in nutrition as risk factors for disease, and then were repurposed to search for potential genomic risk factors for disease. The biomaterials collected from these populations became institutionalized in a data repository that later became a major source of “diverse” DNA for other studies of genomic risk factors for disease. We examine what happened when the MEC biorepository and dataset, organized by ethnic labels, came to be used, in conjunction with the data from the HapMap reference populations, to construct human population genetic categories. Developing theory on genomic racialization, we examine (1) how and why Hawai‘i became sited as a “virtual natural laboratory” for collecting and examining biomaterials from different ethnic groups, and the consequences of the transformation of those local Hawaiian ethnic groups into five racial and ethnic OMB categories meant to represent global continental groups for genomic studies. We then discuss (2) how this transformation, via the geneticists’ effort to standardize the study of genomic risk for disease around the globe, led to the construction of humans as statistical genetic resources and entities for genomic biomedicine and the human population genetics discipline. Through this transformation of populations and biorepositories, we argue (3) that the twenty-first century has seen the intertwining of “race,” “population,” and “genome” via large-scale genomic association studies. We show how “race” has become imbricated in human population genetics and genomic biomedicine. This essay is part of a special issue entitled Pacific Biologies: How Humans Become Genetic, edited by Warwick Anderson and M. Susan Lindee.

Graph Embedding Method Based Genetical Trajectory Reveals Migration History Among East Asians

ABSTRACTAn important issue in human population genetics is the ancestry. By extracting the ancestral information retained in the single nucleotide polymorphism (SNP) of genomic DNA, the history of migration and reproduction of the population can be reconstructed. Since the SNP data of population are multidimensional, their dimensionality reduction can demonstrate their potential internal connections. In this study, the graph and structure learning based Graph Embedding method commonly used in single cell mRNA sequencing was applied to human population genetics research to decrease the data dimension. As a result, the human population trajectory of East Asia based on 1000 Genomes Project was reconstructed to discover the inseparable relationship between the Chinese population and other East Asian populations. These results are visualized from various ancestry calculators such as E11 and K12B. Finally, the unique SNPs along the psudotime of trajectory were found by differential analysis. Bioprocess enrichment analysis was also used to reveal that the genes of these SNPs may be related to neurological diseases. These results will lay the data foundation for precision medicine.