Genetic variants of the mechanosensitive ion channel Piezo1

In the history of evolution, modern humans (Homo sapiens) and Neanderthals, who had a common ancestor around 500,000 to 600,000 years ago, inhabited parts of Africa and Europe simultaneously. This resulted in interbreeding between the two species. The reasons for the extinction of Neanderthals around 35,000 years ago, while Homo sapiens have survived to the present day, are still unclear. Throughout evolution, our ancestors had to adapt to constant changes in their environment, including climate change, shifts in food supply, and the emergence of new pathogens. One hypothesis is that Homo sapiens were superior to Neanderthals in this regard. Adaptation to environmental conditions is also evident in our genetic material, DNA. The decoding of the Neanderthal genome, which was recently awarded the Nobel Prize, has revealed that modern humans differ only slightly from Neanderthals. One of the 87 proteins that occur in a modified form in modern humans is the ion channel PIEZO1. PIEZO1, which was recently awarded the Nobel Prize, plays a crucial role in red blood cells by sensing mechanical signals from the environment and transmitting them into the cell. This is important for the function and flow properties of red blood cells. Changes in PIEZO1 could have given Homo sapiens a significant advantage over Neanderthals in terms of oxygen supply, potentially affecting their performance, reproductive success, and overall survival. Genetic variations in PIEZO1, similar to those seen in today`s population, are linked to functional limitations in red blood cells and, in some cases, malaria resistance. Our research project aims to reproduce the form of the PIEZO1 gene found in Neanderthals within human red blood cells in the cell culture laboratory for the first time. We will use the CRISPR/Cas9 gene editing technology and an innovative cell culture model to produce red blood cells from human stem cells. The function of the Neanderthal ion channel and the cultivated Neanderthal red blood cells will be compared with those of modern humans. In collaboration with PIEZO1 experts from Saarland University (Germany) and evolutionary medicine specialists from the University of Zürich (Switzerland), we will also investigate how today`s PIEZO1 variants are distributed globally among different populations to better understand their evolutionary dynamics. Our study extends beyond genetic research and offers insight into the complexity of human evolution, helping us better understand our collective past and explore the evolutionary paths that lie ahead.