The hyperdisease hypothesis, proposed by Ross MacPhee in 1997, states that the megafaunal die-off was due to an indirect transmission of diseases by newly arriving humans. According to MacPhee, aboriginals or animals travelling with them, such as domestic dogs or livestock, introduced one or more highly virulent diseases into new environments whose native population had no immunity to them, eventually leading to their extinction. K-selection animals, such as the now-extinct megafauna, are especially vulnerable to diseases, as opposed to r-selection animals who have a shorter gestation period and a higher population size. Humans are thought to be the sole cause as other earlier migrations of animals into North America from Eurasia did not cause extinctions. A related theory proposes that a highly contagious prion disease similar to chronic wasting disease or scrapie that was capable of infecting a large number of species was the culprit. Animals weakened by this "superprion" would also have easily become reservoirs of viral and bacterial diseases as they succumbed to neurological degeneration from the prion, causing a cascade of different diseases to spread among various mammal species. This theory could potentially explain the prevalence of heterozygosity at codon 129 of the prion protein gene in humans, which has been speculated to be the result of natural selection against homozygous genotypes that were more susceptible to prion disease and thus potentially a tell-tale of a major prion pandemic that affected humans of or younger than reproductive age far in the past and disproportionately killed before they could reproduce those with homozygous genotypes at codon 129.
