MALARIA AS A SELECTIVE FORCE IN THE PREHISTORY OF THE MEDITERRANEAN BASIN

Malaria is thought to have been a main selective force in human evolution. Indeed, it is still one of the main causes of mortality in developing countries in tropical areas. It’s caused by a protozoan Plasmodium, which is transmitted through the mosquito Anopheles. Its presence in the Mediterranean has been dated to ~10,000 yBP, following the agriculture expansion around the Neolithic. The selective effect of malaria is associated to the persistence of deleterious alleles, which in turn confer resistance against the parasite. One of the best-known examples is the prevalence of thalassemia and sickle cell variants in malaria endemic regions. But when did this selection start? And how strong was it in the Mediterranean basin? These questions have been object of intense research, with most of the studies being based on the observation of correlations between the distribution of the parasite and the resistant variants. Here we present a direct approach, based on the analysis of DNA from ancient humans. We analysed the genomes of more than 300 ancient individuals from Italy and Central Europe, in a time transect of 12000 years (from UP to Medieval times). We studied the changes of allele frequency at loci related to malaria resistance in both datasets, to understand when and to what extent the malaria was an evolutionary force in Europe. Unlike Central Europe, we found an important increase of malaria resistant alleles in Italy around the Bronze Age, especially in Sardinia. What’s more, our analysis showed that the nature and prevalence of protective variants in the beta-globin gene in prehistoric Italy differed from those found in the current populations. Following the times and origins of the different trends in selection towards different resistant alleles, we are reconstructing the times and dynamics of malaria expansion in Italy and the southwest Europe.