Convergent Evolution of Human-Isolated H7N9 Avian Influenza A Viruses.

Background: Avian influenza A virus H7N9 has caused 5 epidemic waves of human infections in China since 2013. Avian influenza A viruses may face strong selection to adapt to novel conditions when establishing themselves in humans. In this study, we sought to determine whether adaptive evolution had occurred in human-isolated H7N9 viruses. Methods: We evaluated all available genomes of H7N9 avian influenza A virus. Maximum likelihood trees were separately reconstructed for all 8 genes. Signals of positive selection and convergent evolution were then detected on branches that lead to changes in host tropism (from avian to human). Results: We found that 3 genes had significant signals of positive selection (all of them P < .05). In addition, we detected 34 sites having significant signals for parallel evolution in 8 genes (all of them P < .05), including 7 well-known sites (Q591K, E627K, and D701N in PB2 gene; R156K, V202A, and L244Q in HA; and R289K in NA) that play roles in crossing species barriers for avian influenza A viruses. Conclusion: Our study suggests that, during infection in humans, H7N9 viruses have undergone adaptive evolution to adapt to their new host environment and that the sites where parallel evolution occurred might play roles in crossing species barriers and respond to the new selection pressures arising from their new host environments.

Convergent Evolution of Mitochondrial Genes in Deep-Sea Fishes.

Deep seas have extremely harsh conditions including high hydrostatic pressure, total darkness, cold, and little food and oxygen. The adaptations of fishes to deep-sea environment apparently have occurred independently many times. The genetic basis of adaptation for obtaining their energy remains unknown. Mitochondria play a central role in aerobic respiration. Analyses of the available 2,161 complete mitochondrial genomes of 1,042 fishes, including 115 deep-sea species, detect signals of positive selection in mitochondrial genes in nine branches of deep-sea fishes. Aerobic metabolism yields much more energy per unit of source material than anaerobic metabolism. The adaptive evolution of the mtDNA may reflect that aerobic metabolism plays a more important role than anaerobic metabolism in deep-sea fishes, whose energy sources (food) are extremely limited. This strategy maximizes the usage of energy sources. Eleven mitochondrial genes have convergent/parallel amino acid changes between branches of deep-sea fishes. Thus, these amino acid sites may be functionally important in the acquisition of energy, and reflect convergent evolution during their independent invasion of the harsh deep-sea ecological niche.

Adaptive Evolution of Human-Isolated H5Nx Avian Influenza A Viruses.

Avian influenza A viruses (AIVs) H5N1, first identified in 1996, are highly pathogenic in domestic poultry and continue to occasionally infect humans. In this study, we sought to identify genetic changes that occurred during their multiple invasions to humans. We evaluated all available H5Nx AIV genomes. Significant signals of positive selection were detected in 29 host-shift branches. 126 parallel evolution sites were detected on these branches, including 17 well-known sites (such as T271A, A274T, T339M, Q591K, E627K, and D701N in PB2; A134V, D154N, S223N, and R497K in HA) that play roles in allowing AIVs to cross species barriers. Our study suggests that during human infections, H5Nx viruses have experienced adaptive evolution (positive selection and convergent evolution) that allowed them to adapt to their new host environments. Analyses of adaptive evolution should be useful in identifying candidate sites that play roles in human infections, which can be tested by functional experiments.

Potential Pandemic of H7N9 Avian Influenza A Virus in Human.

Since 2013, the H7N9 avian influenza A virus (AIV) has caused human infections and to the extent of now surpassing H5N1. This raises an alarm about the potential of H7N9 to become a pandemic problem. Our compilation of the amino acid changes required for AIVs to cross the species-barrier discovers 58 that have very high proportions in both the human- and avian-isolated H7N9 viruses. These changes correspond with sporadic human infections that continue to occur in regions of avian infections. Among the six internal viral genes, amino acid changes do not differ significantly between H9N2 and H7N9, except for V100A in PA, and K526R, D627K, and D701N in PB2. H9N2 AIVs provide internal genes to H7N9. Most of the amino acid changes in H7N9 appear to come directly from H9N2. Seventeen amino acid substitutions appear to have fixed quickly by the 5th wave. Among these, six amino acid sites in HA1 are receptor binding sites, and PB2-A588V was shown to promote the adaptation of AIVs to mammals. The accelerated fixation of mutations may promote the adaptation of H7N9 to human, but need further functional evidence. Although H7N9 AIVs still cannot efficiently transmit between humans, they have the genetic makeup associated with human infections. These viruses must be controlled in poultry to remove the threat of it becoming a human pandemic event.

Evolutionary dynamics of avian influenza A H7N9 virus across five waves in mainland China, 2013-2017.

Since its emergence in March 2013, novel avian influenza A H7N9 virus has triggered five epidemics of human infections in China. This raises concerns about the pandemic threat of this quickly evolving H7N9 subtype for humans. In this study, we evaluated all available genomes for H7N9 and H9N2 influenza A viruses. Our assessment discovered that H7N9 of the 1st wave had the lowest nucleotide diversity, which then experienced substantial and rapid population expansion from a small founder population. From the 2nd wave, their nucleotide diversity increased quickly, indicating that H7N9 viruses had acquired larger populations and mutations after their initial emergence in 2013. After the phylogeographic divergence in the 2nd wave, although the HA and NA genes from different regions differed, compared to previous epidemics, the evolving H7N9 viruses in the 5th wave lost most of their previous clades. The highly pathogenic avian influenza (HPAI) H7N9 viruses in the 5th wave clustered together, and clustered close to the low pathogenic avian influenza (LPAI) virus isolated from the Pearl River Delta in the 3rd and 4th waves. This result supports the origin of HPAI H7N9 viruses was in the Pearl River Delta. In the 5th wave, although both HPAI and LPAI H7N9 viruses were isolated from the Pearl River Delta, their HA and NA genes were phylogenetically distinct.