RESUMEN
SARS-CoV-2 is suspected to be the product of a natural or artificial recombination of two viruses - one adapted to the horseshoe bat and the other, donor of the spike protein gene, adapted to an unknown species. Here we used a new method to search for the original host of the ancestor of the SARS-CoV-2 virus and for the donor of its gene for the spike protein, the molecule responsible for binding to and entering human cells. We computed immunological T-distances (the number of different peptides that are present in the viral proteins but absent in proteins of the host) between 11 species of coronaviruses and 38 representatives of the main mammal clades. Analyses of pentapeptides, the presumed principal targets of T-cell non-self recognition, showed the smallest T-distance of the spike protein of SARS-CoV-2 to humans, while the rest of SARS-CoV-2 proteome to the horseshoe bat. This suggests that the ancestor of SARS-CoV-2 was adapted to bats, but the spike gene donor was adapted to humans. Further analyses suggest that the ancestral coronavirus adapted to bats was shortly passaged in treeshrews, while the donor of the spike gene was shortly passaged in rats before the recombination event.
RESUMEN
Self/non-self-discrimination by vertebrate immune systems is based on the recognition of the presence of peptides in proteins of a parasite that are not contained in the proteins of a host. Therefore, a reduction of the number of 'words' in its own peptide vocabulary could be an efficient evolutionary strategy of parasites for escaping recognition. Here, we compared peptide vocabularies of 30 endoparasitic and 17 free-living unicellular organisms and also eight multicellular parasitic and 16 multicellular free-living organisms. We found that both unicellular and multicellular parasites used a significantly lower number of different pentapeptides than free-living controls. Impoverished pentapeptide vocabularies in parasites were observed across all five clades that contain both the parasitic and free-living species. The effect of parasitism on a number of peptides used in an organism's proteins is larger than effects of all other studied factors, including the size of a proteome, the number of encoded proteins, etc. This decrease of pentapeptide diversity was partly compensated for by an increased number of hexapeptides. Our results support the hypothesis of parasitism-associated reduction of peptide vocabulary and suggest that T-cell receptors mostly recognize the five amino acids-long part of peptides that are presented in the groove of major histocompatibility complex molecules.