The role of Denisovan paleohabitats in shaping modern human genetic resistance to viral, bacterial, and parasitic infections.

Denisovans contributed notably to the genomes of present-day East and Southeast Asians. However, the relationship between the inhabited paleohabitats and the adaptive genetic traits related to infections in modern humans remains underexplored. This study uses geospatial techniques to analyze climatic factors associated with three Denisovan archaeological sites linked to nine specimens. Additionally, past and present climates and biomes, as well as the geographic distributions of eight infectious agents and disease vector groups, were modeled and compared with the modern genetic heritage of Denisovans. Findings reveal that the identified Denisovans inhabited subarctic and monsoon-influenced temperate climates, occupying boreal and seasonal forest biomes in the three studied archaeological sites. Sites such as Denisova Cave and Baishiya Karst Cave exhibited low climatic suitability for Ascaris lumbricoides, visceral leishmaniasis, and Nipah virus. Plasmodium vivax- and Aedes albopictus-like vectors plausibly were also not present. Conversely, Denisova Cave and Baishiya Karst Cave exhibit high climatic suitability for Ixodes persulcatus and Lyme borreliosis when Denisovans inhabited these sites. The paleoenvironment of the Laotian Cobra Cave site-with the exception of Nipah henipavirus-was suitable for all modeled pathogens and vectors. From the studied vectors and diseases, I. persulcatus and Lyme borreliosis are missing from Melanesia, where the region's humans have the highest Denisovan legacy. This suggests that Denisovans from humid continental climates, such as those near Cobra Cave, may have contributed alleles providing adaptive advantages against ascariasis and mosquito-borne diseases in environments where modern human populations with high Denisovan genetic legacy reside.