Cavalli-Sforza first made his mark in his native Italy, traveling to villages in the Parma Valley to sample blood. He worked to understand how inbreeding within these small towns was connected to the slight differences in frequency of blood groups. With several coworkers, he scoured church records of marriages and births, tracing the times when people moved between villages as well as the number of children they had. Tracing these multiple lines of evidence, he could show that consanguineous marriages, or inbreeding, were the main drivers of genetic differences between these small towns. In doing so, he provided some of the earliest evidence that humans were still being affected by genetic drift, the random change in gene frequencies that happens in small populations.

Cavalli-Sforza realized that if genetic drift could explain the gene frequencies in small Italian towns, it might have affected humanity over a much deeper past. Genetic drift was a force that over long periods of time tended to drive populations slowly apart, inexorably diverging in gene frequencies. Applied to a group of populations over long periods of time, genetic drift would form a tree.

It was during this period that Cavalli-Sforza began collaborating with the statistical geneticist A. W. F. Edwards, developing ways to reconstruct evolutionary trees from gene frequencies. The statistical methods used measures of distance, computed from the frequencies of several genes across populations, and they generated a new picture of human origins.

From Cavalli-Sforza 1966, “Population structure and human evolution.”

Here, the branches of humanity came into focus. American Indians, Asians, and Oceanians on one broad branch, Europeans and Africans on the other.

The tree looks very different from our understanding today, which places African populations as the most diverse elements of humanity, not a minor twig. It is worth noting why Cavalli-Sforza’s early trees turned out to be wrong. Blood groups were first discovered and studied in people of European descent, meaning that African variation was not fully included by looking at the traits that vary in Europe. These five loci in particular include several that reflect natural selection, especially the Fy, or Duffy, locus, which approaches fixation in many sub-Saharan populations. Today, using whole genome sequences, it is clear that the deepest branches of human population trees are African.

But more important, the tree illustrates an enormous limitation of the classical markers. The frequencies of a few genes simply do not provide enough information to tell when and how much mixture may have happened among the populations. Cavalli-Sforza, drawing upon his work in the Parma Valley, and later work with Pygmies in central Africa, was willing to assume that migration and mixture were rare. In his model genetic drift, not gene flow, was the main force driving human evolution. Natural selection happened, too, but with patterns that might be recognized by comparing to the predictions of genetic drift alone.

A tree for visualizing genetic differences was a powerful tool. But Cavalli-Sforza and Edwards went a step further. They used an early computer to take the genetic differences between populations and transform them into principal components, which reflected the common correlations among the gene frequencies.

The first principal component of genetic variation across Europe, from Cavalli-Sforza 1997 Proc. Nat. Acad. Sci USA.

With this approach, they could not only show how gene frequencies changed on a map; they could now show how the common correlation of many gene frequencies changed. In Cavalli-Sforza’s vision, these maps provided a view of the historical forces that caused people to vary. A gradient across all the classical markers could show the possible pathways of movement and migration in the past. What the maps couldn’t show was how and why those movements had happened.

“The results of principal components analyses looked very good, but there was nothing to compare them with because the questions they helped to answer had never been asked”

He set out to find other sources of data that could make the genetic distances meaningful. With the archaeologist A. J. Ammerman, Cavalli-Sforza turned his attention to the Neolithic. This was an epochal archaeological change: the time that agriculture first spread from the Near East into Europe, taking with it pottery and stone implements that were ground and polished rather than chipped and flaked into shape. If events of the past had been powerful enough to sculpt gene frequencies across Europe, it seemed that the Neolithic should have been the strongest of them all.

By the early 1970s, the radiocarbon revolution had taken hold across European archaeological sites. The earliest signs of Neolithic traditions in various regions of Europe, from Greece to Ireland, had been dated with the new method. And they formed a striking pattern: it appeared that the Neolithic had spread slowly, around one kilometer a year, from the southeast to the northwest.

For Cavalli-Sforza, this picture had a clear implication: No migrating horde of farmers had colonized Europe. Instead, farming spread as farming populations gradually increased in size, carrying their new way of life to the next small region or hamlet. This process seemed almost to ignore variations in environment such as forest or hills, it seemed to have been inexorable. It was not the mere diffusion of ideas, instead it was a diffusion of culture together with genes. It was, as Ammerman and Cavalli-Sforza would name it, a process of demic diffusion.

“All evolutionary processes are basically similar, whichever the objects that evolve.”

During the 1980s and 1990s, demic diffusion became the dominant model of demographic change for the Neolithic. The idea underlay Colin Renfrew’s influential theory that Indo-European languages also spread with the Neolithic into Europe, replacing earlier languages spoken by Mesolithic or earlier peoples. It appeared that the processes of culture change and dispersal could be linked to the growth and expansion of human groups, if only geneticists could fill in the gaps in their data. Cavalli-Sforza worked more and more to understand how cultural and biological changes were linked, establishing a long-lasting collaboration with Marc Feldman to examine how cultures evolve.

We know today from ancient DNA data that the details of this vision of the Neolithic were wrong. The expansion of agriculture was important, but it was not alone. Much later movements of people, some of them quite rapid, transformed the genetic makeup of European populations. Today it appears that Indo-European languages invaded Europe during the Bronze Age, and that early farmers were genetically most like today’s Sardinians, a linguistic isolate that Cavalli-Sforza knew well.

But those facts learned from ancient DNA have come to most geneticists as a surprise. The synthetic view promoted by Cavalli-Sforza was so compelling, linking economic, demographic, and genetic change, that it would take a new data revolution — still underway today — to overturn.