Infectious diseases that jump from animals to humans, so-called zoonoses, can spread into global pandemics like COVID-19 and are therefore always a concern. Until now, a widely held view in the scientific community was that for such viruses to spread among humans, they must first evolve to some extent within animal hosts in ways favorable to human infection.
But researchers at the University of California, San Diego (UC San Diego) published findings on the 6th (local time) in the journal Cell that question this conventional wisdom. They reported that for most zoonotic viruses, they found no clear signs that the viruses underwent special, human-specific evolution before spilling over to people.
The team compared the genomes of multiple viruses that caused influenza A, Ebola, Marburg, mpox, SARS, and COVID-19. In particular, they focused on the period just before outbreaks began in human populations. If a virus evolved before crossing into humans, they reasoned, traces of that evolution should remain in its genome.
For example, some genetic mutations are advantageous to a virus and spread more, while others are disadvantageous and disappear. The environmental pressure that makes certain genetic changes more likely to persist is called "selection pressure" or "evolutionary pressure." The researchers said that by examining this pattern, they could infer whether a virus adapted to the human body or to laboratory conditions.
The analysis found little discernible difference between viruses circulating in animal hosts and those just before spilling over to humans. In other words, there was no evidence that the virus suddenly changed strongly in a direction favorable to human infection immediately before large-scale human transmission. Instead, noticeable changes often appeared after the virus began spreading in earnest among people.
The 2009 swine flu is a representative example. The virus is known to have originated in pigs, and until it crossed to humans, it did not differ much from the usual evolutionary patterns seen in swine influenza viruses. But once it entered human populations, it changed to spread more effectively in the new host.
The results also touch on the debate over the origins of COVID-19. Jay Bhattacharya, director of the U.S. National Institutes of Health, said in an interview with The New York Times (NYT) in Jan. that SARS-CoV-2, the virus that causes COVID-19, originated in a laboratory. In contrast, a World Health Organization (WHO) expert group concluded that SARS-CoV-2 originated in bats and was likely transmitted to animals sold at a market in Wuhan, China.
Joel Wertheim of UC San Diego said, "From an evolutionary perspective, we found no evidence that SARS-CoV-2 underwent selection in a laboratory or evolved in a special way for a long time in an intermediate host," adding, "It matches what one would expect from natural animal-to-human transmission. This can serve as another basis to counter claims that the COVID-19 virus was engineered in a lab."
By contrast, the H1N1 influenza virus that caused the 1977 Russian flu showed a different pattern. Genetically, it was excessively similar to viruses that circulated in the 1950s, making it hard to conclude it evolved naturally over a long period. The researchers said, "Its evolutionary pattern also resembled viruses repeatedly passaged in laboratories rather than natural transmission," calling it "new evidence supporting the long-standing suspicion that it may have arisen during vaccine experiments."
Based on this study, the team explained that "many viruses may already exist in nature with a baseline potential to infect humans and to spread among people to some degree."
Wertheim said, "Thus, at the starting point of a pandemic, what may matter more than how perfectly a virus has evolved is how frequently people are exposed to diverse animal viruses," adding, "Pandemic preparedness should focus less on trying to preemptively find specific 'super viruses' and more on reducing points of contact among wildlife, livestock, and humans and on detecting warning signs early."
References
Cell (2026), DOI: https://doi.org/10.1016/j.cell.2026.02.006