Skip to main content

Evolutionary history of the sickle cell trait among Central African hunter-gatherers and farmers

Periodic Reporting for period 1 - PreNeolithicMalaria (Evolutionary history of the sickle cell trait among Central African hunter-gatherers and farmers)

Reporting period: 2019-05-01 to 2021-04-30

The 'PreNeolithic Malaria' project investigates the Paleolithic origin of human genetic traits that confer protections against deadly malarial infections. By applying cutting-edge methods, the project explored the genetics of Central African populations with different subsistence economies, either based prevalently on farming or hunting-gathering. Both groups of populations are known to be affected by genetically inherited blood disorders that confer them a variable level of protection from strong malarial infections, by allowing them to keep the infection at low levels. These blood disorders are caused by different kinds of genetic mutations, which are transmitted from one generation to the other as long as malaria is endemic in the environment where the populations live. Such evolutionary adaptation is linked to a double public health problem: the first is the need for people to survive malarial infections, not yet eradicated in many parts of the world with limited access to medical treatment; the second is caused by the mutations causing blood diseases that are protective from malaria but also can be damaging for the carrier. This scenario is considered as an evolutionary trade-off that allows populations living in malarial endemic areas to survive the infections at the cost of losing the lives of individuals who are affected by severe inherited blood conditions. As many of the populations living in malarial areas are very little studied from a medical genetic perspective, the genetic basis of their inherited blood conditions is also limitedly known. This project serves the double aim of studying in deep the genetic underlying blood disorders in these populations, both known and unknown, and, at the same time, understanding the ultimate evolutionary origin of human adaptation to a deadly parasite (the malarial causal parasite) which has affected our species for thousands of years.

Conclusions of the action: The results so far obtained from the preliminary data analysis suggest a high variation of genetic variants protecting from malaria in hunter-gatherers, some of which are known to be mostly present in populations outside of Africa and differ from those carried by neighboring farmers. As such, my results point to an ancient adaptation to malarial parasites in hunter-gatherers
The work done during the duration of the project has led to an extended data collection of highly valuable human genetic sequences. My results point at supporting my working hypothesis with many relevant aspects for publication. I have disseminated my results mainly to the department through internal seminars, as I am waiting to finalize all the relevant statistical analyses before sharing my findings with the broader scientific community. I am currently working on finalizing three independent papers, one of which is in collaboration with a student and I will sign a senior author.

Overview of the results and their exploitation and dissemination: My data analysis has pinpointed a series of known mutations that are linked to thalassemias and the sickle cell anemias in all the populations analyzed. Hunter-gatherers present some mutations that are already known but not detected in their neighboring farmers. Some unknown and possibly pathogenic mutations have also been detected and are currently under further investigation. The population-based analysis will clarify whether protective mutations found in both hunter-gatherers and farmers have an independent origin or have a single origin and have thus spread from one group to the others. All results are being collected into three scientific publications that are expected to be submitted during the coming months. I will be thus able to share the results of my work at scientific meetings towards the end of this year and next year.
The impact of this project relies mainly on two aspects: the contribution to our knowledge of the genetic basis of inherited blood diseases in medically underrepresented populations, and a new understanding of our cultural to biological adaptation during a main transition of human history.

The socio-economic impact and the wider societal implications of the project so far: my results will be used in public health to improve the prophylaxis of individuals affected by anemia. The knowledge of local mutations potentially linked to genetically determined anemia will help local public health authorities to include these mutations in testing and treatment.
@Survival International