The timing and cause of rapid extinctions of the megafauna, that roamed the plains of Patagonia in southern South America, has remained a mystery for centuries.
"Patagonia turns out to be the Rosetta Stone - it shows that human colonisation didn't immediately result in extinctions, but only as long as it stayed cold," said Alan Cooper, professor at the University of Adelaide in Australia.
The researchers, including from the University of Colorado Boulder in the US, University of New South Wales in Australia and University of Magallanes in Chile, studied ancient DNA extracted from radiocarbon-dated bones and teeth found in caves across Patagonia, and Tierra del Fuego, to trace the genetic history of the populations.
Species such as the South American horse, giant jaguar and sabre-toothed cat, and the enormous one-tonne short-faced bear (the largest land-based mammalian carnivore) were found widely across Patagonia, but seemed to disappear shortly after humans arrived.
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"The America's are unique in that humans moved through two continents, from Alaska to Patagonia, in just 1500 years," said Chris Turney, professor at the University of New South Wales.
"As they did so, they passed through distinctly different climate states - warm in the north, and cold in the south. As a result, we can contrast human impacts under the different climatic conditions," Turney said.
The only large species to survive were the ancestors of today's llama and alpaca - the guanaco and vicuna - and even these species almost went extinct.
The study was published in the journal Science Advances.