Defining the Predicted Blood Group Phenotype of Archaic Hominin, Homo Denisovan, and Its Potential Clinical Significance for Disease Association and Relationship to Phenotypes of Modern Homo sapiens

Abstract

Homo denisovan is one of the extinct ancient hominins who lived more than 30,000 years ago. Unlike their sister group, the Neandertals, who lived during the same time period, there is little information available today about the Denisovans. However, their whole genome sequence has recently become available and was used in this project to examine the blood group, erythropoiesis and red blood cell cytoskeleton-associated genes. In this project, 44 genes encoding blood groups were analysed to elucidate the Denisovan blood group genotypes and predicted phenotypes, which were previously unknown. Furthermore, 12 genes involved in erythropoiesis and red blood cell cytoskeleton were analysed and compared to modern humans. Interestingly, 52 novel single nucleotide variations (SNVs) were detected, of which 55% may have altered blood group antigen expression (e.g. in the Lutheran system), or introduced new blood group phenotypes that have not been reported in modern humans (e.g. in Kell and Knops systems). Moreover, The Denisovan had O blood group predicted phenotype. One interesting finding was the Memphis variant I observed with Diego(a-b+) phenotype, which is considered rare in modern humans. On the other hand, in cytoskeleton related genes, the Denisovan has several SNVs reported to be associated with different red blood cell membrane abnormalities, such as heredity spherocytosis. Furthermore, the Denisovan had a significant number of SNVs in genes involved in erythropoiesis, that might have altered the functions of the encoded proteins. This project will help expand our knowledge about blood group evolution and the factors influencing these changes.