Ancient Adaptative Evolution of ACE2 in East Asians

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been posing an unprecedented challenge to global public health. SARS-CoV-2 and several other coronaviruses utilize angiotensin-converting enzyme 2 (ACE2) as their entry receptors. The ACE2 gene has been found to experience episodic positive selection across mammals. However, much remains unknown about how the ACE2 gene evolved in human populations. Here, we use population genetics approaches to investigate the evolution of the ACE2 gene in 26 human populations sampled globally. We find the ACE2 gene exhibits an extremely low nucleotide diversity in the East Asian populations. Strong signals of selective sweep are detected in the East Asian populations, but not in the other human populations. The selective sweep in ACE2 is estimated to begin in East Asian populations ∼23,600 years ago. Our study provides novel insights into the evolution of the ACE2 gene within human populations.