Interview with Luigi Luca Cavalli-Sforza: Past Research and Directions for Future Investigations in Human Population Genetics

Biographical Notes

Luigi Luca Cavalli-Sforza (M.D., Pavia, 1944), started doing research on sex in bacteria and the origin of resistance to antibiotics. In the early 1950s he moved to research in human population genetics and evolution, showing the major role played by random genetic drift and how to take into account this evolutionary factor for a better reconstruction of the evolutionary origin of human populations. To this end, Cavalli-Sforza analyzed a great variety of genetic data, from blood groups and proteins to mitochondrial and Y-chromosome DNA. Later he investigated the variability of microsatellites, and SNP megachips. All these markers gave coherent conclusions about human history and corroborated the "out of Africa" model, which he largely developed.

Among Cavalli-Sforza's major achievements are his investigations of human evolution using a multidisciplinary approach that includes genetics, demography, anthropology, archaeology, and linguistics. This approach led, among other things, to the establishment of important parallels between genetic and linguistic variability on a global scale.

Cavalli-Sforza contributed greatly to a worldwide collection of cell lines representing many aboriginal populations in what is known as the Human Genome Diversity Project (HGDP). The cell lines are maintained at the CEPH-Fondation Jean Dausset in Paris and are intended to provide a large amount of DNA for current genetic investigations; more than a hundred laboratories have used the cell lines. Using a similar approach, Cavalli-Sforza is currently generating an Italian Genome Project to aid in research in medical genetics.

Among other projects, Cavalli-Sforza is the general editor of La Cultura Italiana (Italian Culture), an ambitious encyclopedic work that he has conceived and that will consist of 12 volumes published by UTET (Turin, Italy). This work, almost completed, will hopefully be translated into English, as it is intended to provide Italian Americans with a historical and cultural background of their homeland.

Luigi Luca Cavalli-Sforza at the conference "Archaeology and Genetics: Towards (Integrated) Archaeogenetics" (Seix, France, June 2-5, 2004). Courtesy of Franz Manni.

Cavalli-Sforza can be considered one of the founders of modern human population genetics. His works had, and still have, a profound influence on genetic and anthropological research.

Franz Manni:

As you probably remember, some years ago Human Biology published a couple of commentaries by Robert R. Sokal about possible flaws in the way principal components analysis (PCA) displays genetic variation (Sokal et al. 1999a, 1999b). Notwithstanding such comments, the technique has become really popular and still is today. I am mentioning this issue because there has recently been a more detailed criticism to the use of PCA in human population genetics (Novembre and Stephens 2008). I am not aware of any public response to Novembre and Stephens by you or your co-workers, and I would like to know whether you still believe that PCA is an appropriate method to analyze geographic patterns of genetic variation or if you recommend using different methodologies.

L. L. Cavalli-Sforza:

Principal components analysis is an excellent method published by Hotelling (1933) and was very rarely used until the advent of electronic computers because the technique is computationally very intensive. Along with other novel methods to reconstruct evolutionary trees, Anthony Edwards and I were the first to apply PCA to human genetic data (Cavalli-Sforza and Edwards 1965). Later, together with Paolo Menozzi and Alberto Piazza (Menozzi et al. 1978), I used the geographic maps of the first three principal components (PCs) to test the possible genetic expansions observable in Europe. The map of the first PC showed a very remarkable similarity with the archeological map of the Neolithic expansion in Europe, the latter being obtained by plotting the sites where the presence of plants with a Middle Eastern origin was documented and dated, like wheat. The first PC accounted for a...