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While worldwide efforts for improving COVID-19 vaccines are currently considered a top priority, the role of the genetic variants responsible for virus receptor protein stability is less studied. Angiotensin-converting enzyme-2 is the primary target of the SARS-CoV-1/SARS-CoV-2 spike (S) glycoprotein, enabling entry into the human body. Here, we applied computational saturation mutagenesis approaches to determine the folding energy caused by all possible mutations in ACE2 proteins within ACE2 - SARS-CoV-1-S/ACE2 - SARS-CoV-2-S complexes. We observed ACE2 mutations at residue D350 causing the most stabilizing effects on the protein. In addition, we identified ACE2 genetic variations in African Americans (rs73635825, rs766996587, and rs780574871), Latino Americans (rs924799658), and both groups (rs4646116 and rs138390800) affecting stability in the ACE2 - SARS-CoV-2-S complex. The findings in this study may aid in targeting the design of stable neutralizing peptides for treating minority patients. 

The term “ancient DNA” (aDNA) is coming of age, with over 1200 hits in the PubMed database, beginning in the early 1980s with the studies of “molecular paleontology.” Rooted in cloning and limited sequencing of DNA from ancient remains during the pre-PCR era, the field has made incredible progress since the introduction of PCR and next-generation sequencing. Over the last decade, aDNA analysis ushered in a new era in genomics and became the method of choice for reconstructing the history of organisms, their biogeography, and migration routes, with applications in evolutionary biology, population genetics, archaeo-genetics, paleo-epidemiology, and many other areas. This change was brought by development of new strategies for coping with the challenges in studying aDNA due to damage and fragmentation, scarce samples, significant historical gaps, and limited applicability of population genetics methods. In this review, we describe the state-of-the-art achievements in aDNA studies, with particular focus on human evolution and demographic history. We present the current experimental and theoretical procedures for handling and analyzing highly degraded aDNA. We also review the challenges in the rapidly growing field of ancient epigenomics. Advancement of ancient DNA tools and methods signifies a new era in population genetics and evolutionary medicine research.