Early humans’ migration out of Africa holds clues for medical research

Evolutionary changes in the human genome point to new approaches for the treatment of disease.

The study explores the genetic legacy of our ancestors' initial journey out of Africa. Credit: Garvan

25 May 2023

Evolutionary changes that helped our early ancestors survive the first migration out of Africa could hold important clues for medical research today, according to an international team of scientists co-led by Professor Shane Grey from the Garvan Institute of Medical Research.

The researchers used ancient human genomes to reconstruct human adaption during the poorly understood “Out of Africa” diaspora for the first time. 

The team found specific genetic patterns that pointed to a series of natural selection events dating back 80,000 years. These patterns suggest the ancestors of modern humans living outside of Africa experienced an extended period of genetic isolation and adaptation, possibly around the Arabian Peninsula, prior to their worldwide dispersal 50,000 years ago. 

“These ancient adaptive genes share striking functional similarities with selected genes found in human and mammalian populations currently living in cooler climates,” said Professor Grey.

These adaptive genetic patterns included genes that regulate body fat (e.g. PPARD, SMCO2), skin colour and DNA damage response (e.g. MLPH, TP53BP1), but also brain function (e.g. DOK5, MPP6). “These show how the natural environment can influence many different elements of human physiology,” he said. 

The study proposes a connection between genetic selection and human migration during the Eurasian Palaeolithic period, suggesting that the speed of movement was influenced not only by climatic cycles but also by the need to adapt to new environments.

Co-first author Dr Raymond Tobler from ANU said it was likely a critical time in human evolution. 

“Ancient human genomes make it possible to recover key events in the evolution of our species that are essentially hidden from modern human genomes,” Dr Tobler said.

“We suspect the ‘Arabian Standstill’ period was a pivotal point in our evolutionary history, during which the ancestors of all non-African humans underwent extensive genetic adaptation to colder environments, effectively preparing them for the cool Eurasian environments they would eventually encounter.”

“Many of these adaptive genes have links to modern diseases, including obesity, diabetes, and cardiovascular disorders. The adaptations around the human expansion from Africa may have established genetic variations that, under modern conditions, are associated with common diseases,” added Professor Grey.

“This study not only improves our understanding of human evolution, but the link between adaptation and modern disease could expedite the development of therapeutic and preventive measures by prioritising medical research on previously selected genes,” co-first author Dr Yassine Souilmi from The University of Adelaide and ANU said.

The study was published in the Proceedings of the National Academy of Sciences

Professor Shane Grey is Head of the Transplantation Immunology Laboratory at Garvan, Head of the School of Biotechnology and Biomolecular Sciences at UNSW Sydney and a Conjoint Associate Professor at St Vincent’s Clinical School, UNSW Sydney.