Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary remain contentious. We use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, underscoring the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.

The mechanisms of Late Pleistocene megafauna extinctions remain fiercely contested, with human impact or climate change cited as principal drivers. We compared ancient DNA and radiocarbon data from 31 detailed time series of regional megafaunal extinctions and replacements over the past 56,000 years with standard and new combined records of Northern Hemisphere climate in the Late Pleistocene. Unexpectedly, rapid climate changes associated with interstadial warming events are strongly associated with the regional replacement or extinction of major genetic clades or species of megafauna. The presence of many cryptic biotic transitions before the Pleistocene/Holocene boundary revealed by ancient DNA confirms the importance of climate change in megafaunal population extinctions and suggests that metapopulation structures necessary to survive such repeated and rapid climatic shifts were susceptible to human impacts.

Whatever the cause, it is extraordinary that dozens of genera of large mammals became extinct during the late Quaternary throughout the Western Hemisphere, including 90% of the genera of the xenarthran suborder Phyllophaga (sloths). Radiocarbon dates directly on dung, bones, or other tissue of extinct sloths place their ''last appearance'' datum at Ϸ11,000 radiocarbon years before present (yr BP) or slightly less in North America, Ϸ10,500 yr BP in South America, and Ϸ4,400 yr BP on West Indian islands. This asynchronous situation is not compatible with glacial-interglacial climate change forcing these extinctions, especially given the great elevational, latitudinal, and longitudinal variation of the slothbearing continental sites. Instead, the chronology of last appearance of extinct sloths, whether on continents or islands, more closely tracks the first arrival of people.