The 2009 swine-origin H1N1 influenza A virus (S-OIV) emerged in Mexico and the United States in March and early April 2009, causing a global pandemic. Evolutionary analysis shows that the virus originated from multiple swine influenza lineages, with initial human transmission occurring several months before the outbreak was recognized. Phylogenetic studies indicate a long period of unsampled ancestry before the outbreak, suggesting that reassortment of swine lineages occurred years before human emergence. The multiple genetic ancestry of S-OIV is not indicative of an artificial origin. The study highlights the need for systematic surveillance of influenza in swine, as mixing of new genetic elements in swine can lead to the emergence of pandemic viruses in humans. The S-OIV genome was derived from a triple-reassortant virus circulating in North American swine, which contained genes from avian, human, and classical swine lineages. The NA and M genes originated from the Eurasian avian-like swine H1N1 lineage. The study included 15 newly sequenced swine influenza viruses from Hong Kong, revealing a mix of H1N1 and H1N2 subtypes, including classical, Eurasian avian-like, and triple-reassortant lineages. Reassortment among these lineages occurred as early as 2003. Phylogenetic analysis of the S-OIV outbreak showed that the progenitor virus originated in pigs, with some transmission to secondary hosts like turkeys. The long unsampled history of the epidemic suggests that the reassortment of Eurasian and North American swine lineages may not have occurred recently. The common ancestor of the S-OIV outbreak and related swine viruses existed between 9.2 and 17.2 years ago, indicating that the ancestors of the epidemic had been circulating undetected for about a decade. The study also found that the S-OIV outbreak had a higher non-synonymous to synonymous substitution rate ratio, which could be due to increased detection of mildly deleterious mutations or increased adaptive evolution. Correcting for this ratio made the estimated time of the most recent common ancestor (TMRCA) more recent. The study emphasizes the importance of systematic swine surveillance to detect and understand the emergence of pandemic influenza viruses. The findings suggest that domestic pigs play a crucial role in the evolution and emergence of influenza viruses, highlighting the need for continued research and surveillance.The 2009 swine-origin H1N1 influenza A virus (S-OIV) emerged in Mexico and the United States in March and early April 2009, causing a global pandemic. Evolutionary analysis shows that the virus originated from multiple swine influenza lineages, with initial human transmission occurring several months before the outbreak was recognized. Phylogenetic studies indicate a long period of unsampled ancestry before the outbreak, suggesting that reassortment of swine lineages occurred years before human emergence. The multiple genetic ancestry of S-OIV is not indicative of an artificial origin. The study highlights the need for systematic surveillance of influenza in swine, as mixing of new genetic elements in swine can lead to the emergence of pandemic viruses in humans. The S-OIV genome was derived from a triple-reassortant virus circulating in North American swine, which contained genes from avian, human, and classical swine lineages. The NA and M genes originated from the Eurasian avian-like swine H1N1 lineage. The study included 15 newly sequenced swine influenza viruses from Hong Kong, revealing a mix of H1N1 and H1N2 subtypes, including classical, Eurasian avian-like, and triple-reassortant lineages. Reassortment among these lineages occurred as early as 2003. Phylogenetic analysis of the S-OIV outbreak showed that the progenitor virus originated in pigs, with some transmission to secondary hosts like turkeys. The long unsampled history of the epidemic suggests that the reassortment of Eurasian and North American swine lineages may not have occurred recently. The common ancestor of the S-OIV outbreak and related swine viruses existed between 9.2 and 17.2 years ago, indicating that the ancestors of the epidemic had been circulating undetected for about a decade. The study also found that the S-OIV outbreak had a higher non-synonymous to synonymous substitution rate ratio, which could be due to increased detection of mildly deleterious mutations or increased adaptive evolution. Correcting for this ratio made the estimated time of the most recent common ancestor (TMRCA) more recent. The study emphasizes the importance of systematic swine surveillance to detect and understand the emergence of pandemic influenza viruses. The findings suggest that domestic pigs play a crucial role in the evolution and emergence of influenza viruses, highlighting the need for continued research and surveillance.