Origin of the OAS-RNase L innate immune pathway before the rise of jawed vertebrates via molecular tinkering.

Discriminating self from nonself is fundamental to immunity. Yet, it remains largely elusive how the mechanisms of self and nonself discrimination originated. Sensing double-stranded RNA as nonself, the 2',5'-oligoadenylate synthetase (OAS)-ribonuclease L (RNase L) pathway represents a crucial component of innate immunity. Here, we combine phylogenomic and functional analyses to show that the functional OAS-RNase L pathway likely originated through tinkering with preexisting proteins before the rise of jawed vertebrates during or before the Silurian period (444 to 419 Mya). Multiple concerted losses of OAS and RNase L occurred during the evolution of jawed vertebrates, further supporting the ancient coupling between OAS and RNase L. Moreover, both OAS and RNase L genes evolved under episodic positive selection across jawed vertebrates, suggesting a long-running evolutionary arms race between the OAS-RNase L pathway and microbes. Our findings illuminate how an innate immune pathway originated via molecular tinkering.

The origin and evolution of a plant resistosome.

The nucleotide-binding, leucine-rich receptor (NLR) protein HOPZ-ACTIVATED RESISTANCE 1 (ZAR1), an immune receptor, interacts with HOPZ-ETI-DEFICIENT 1 (ZED1)-related kinases (ZRKs) and AVRPPHB SUSCEPTIBLE 1-like proteins to form a pentameric resistosome, triggering immune responses. Here, we show that ZAR1 emerged through gene duplication and that ZRKs were derived from the cell surface immune receptors wall-associated protein kinases (WAKs) through the loss of the extracellular domain before the split of eudicots and monocots during the Jurassic period. Many angiosperm ZAR1 orthologs, but not ZAR1 paralogs, are capable of oligomerization in the presence of AtZRKs and triggering cell death, suggesting that the functional ZAR1 resistosome might have originated during the early evolution of angiosperms. Surprisingly, inter-specific pairing of ZAR1 and AtZRKs sometimes results in the formation of a resistosome in the absence of pathogen stimulation, suggesting within-species compatibility between ZAR1 and ZRKs as a result of co-evolution. Numerous concerted losses of ZAR1 and ZRKs occurred in angiosperms, further supporting the ancient co-evolution between ZAR1 and ZRKs. Our findings provide insights into the origin of new plant immune surveillance networks.

A Long-Running Arms Race between APOBEC1 Genes and Retroviruses in Tetrapods.

Activation-induced cytidine deaminase/apolipoprotein B mRNA editing catalytic polypeptide-like (AID/APOBEC) proteins are cytosine deaminases implicated in diverse biological functions. APOBEC1 (A1) proteins have long been thought to regulate lipid metabolism, whereas the evolutionary significance of A1 proteins in antiviral defense remains largely obscure. Endogenous retroviruses (ERVs) document past retroviral infections and are ubiquitous within the vertebrate genomes. Here, we identify the A1 gene repertoire, characterize the A1-mediated mutation footprints in ERVs, and interrogate the evolutionary arms race between A1 genes and ERVs across vertebrate species. We find that A1 genes are widely present in tetrapods, recurrently amplified and lost in certain lineages, suggesting that A1 genes might have originated during the early evolution of tetrapods. A1-mediated mutation footprints can be detected in ERVs across tetrapods. Moreover, A1 genes appear to have experienced episodic positive selection in many tetrapod lineages. Taken together, we propose that a long-running arms race between A1 genes and retroviruses might have persisted throughout the evolutionary course of tetrapods. IMPORTANCE APOBEC3 (A3) genes have been thought to function in defense against retroviruses, whereas the evolutionary significance of A1 proteins in antiviral defense remains largely obscure. In this study, we identify the A1 gene repertoire, characterize the A1-mediated mutation footprints in endogenous retroviruses (ERVs), and explore the evolutionary arms race between A1 genes and ERVs across vertebrate species. We found A1 proteins originated during the early evolution of tetrapods, and detected the footprints of A1-induced hypermutations in retroviral fossils. A1 genes appear to have experienced pervasive positive selection in tetrapods. Our study indicates a long-running arms race between A1 genes and retroviruses taking place throughout the evolutionary course of tetrapods.

Strong and consistent effects of waterbird composition on HPAI H5 occurrences across Europe.

Since 2014, highly pathogenic avian influenza (HPAI) H5 viruses of clade 2.3.4.4 have been dominating the outbreaks across Europe, causing massive deaths among poultry and wild birds. However, the factors shaping these broad-scale outbreak patterns, especially those related to waterbird community composition, remain unclear. In particular, we do not know whether these risk factors differ from those of other H5 clades. Addressing this knowledge gap is important for predicting and preventing future HPAI outbreaks. Using extensive waterbird survey datasets from about 6883 sites, we here explored the effect of waterbird community composition on HPAI H5Nx (clade 2.3.4.4) spatial patterns in the 2016/2017 and 2020/2021 epidemics in Europe, and compared it with the 2005/2006 HPAI H5N1 (clade 2.2) epidemic. We showed that HPAI H5 occurrences in wild birds in the three epidemics were strongly associated with very similar waterbird community attributes, which suggested that, in nature, similar interspecific transmission processes operate between the HPAI H5 subtypes or clades. Importantly, community phylogenetic diversity consistently showed a negative association with H5 occurrence in all three epidemics, suggesting a dilution effect of phylogenetic diversity. In contrast, waterbird community variables showed much weaker associations with HPAI H5Nx occurrence in poultry. Our results demonstrate that models based on previous epidemics can predict future HPAI H5 patterns in wild birds, implying that it is important to include waterbird community factors in future HPAI studies to predict outbreaks and improve surveillance activities.

Functional traits explain waterbirds' host status, subtype richness, and community-level infection risk for avian influenza.

Species functional traits can influence pathogen transmission processes, and consequently affect species' host status, pathogen diversity, and community-level infection risk. We here investigated, for 143 European waterbird species, effects of functional traits on host status and pathogen diversity (subtype richness) for avian influenza virus at species level. We then explored the association between functional diversity and HPAI H5Nx occurrence at the community level for 2016/17 and 2021/22 epidemics in Europe. We found that both host status and subtype richness were shaped by several traits, such as diet guild and dispersal ability, and that the community-weighted means of these traits were also correlated with community-level risk of H5Nx occurrence. Moreover, functional divergence was negatively associated with H5Nx occurrence, indicating that functional diversity can reduce infection risk. Our findings highlight the value of integrating trait-based ecology into the framework of diversity-disease relationship, and provide new insights for HPAI prediction and prevention.

Molecular fossils illuminate the evolution of retroviruses following a macroevolutionary transition from land to water.

The ancestor of cetaceans underwent a macroevolutionary transition from land to water early in the Eocene Period >50 million years ago. However, little is known about how diverse retroviruses evolved during this shift from terrestrial to aquatic environments. Did retroviruses transition into water accompanying their hosts? Did retroviruses infect cetaceans through cross-species transmission after cetaceans invaded the aquatic environments? Endogenous retroviruses (ERVs) provide important molecular fossils for tracing the evolution of retroviruses during this macroevolutionary transition. Here, we use a phylogenomic approach to study the origin and evolution of ERVs in cetaceans. We identify a total of 8,724 ERVs within the genomes of 25 cetaceans, and phylogenetic analyses suggest these ERVs cluster into 315 independent lineages, each of which represents one or more independent endogenization events. We find that cetacean ERVs originated through two possible routes. 298 ERV lineages may derive from retrovirus endogenization that occurred before or during the transition from land to water of cetaceans, and most of these cetacean ERVs were reaching evolutionary dead-ends. 17 ERV lineages are likely to arise from independent retrovirus endogenization events that occurred after the split of mysticetes and odontocetes, indicating that diverse retroviruses infected cetaceans through cross-species transmission from non-cetacean mammals after the transition to aquatic life of cetaceans. Both integration time and synteny analyses support the recent or ongoing activity of multiple retroviral lineages in cetaceans, some of which proliferated into hundreds of copies within the host genomes. Although ERVs only recorded a proportion of past retroviral infections, our findings illuminate the complex evolution of retroviruses during one of the most marked macroevolutionary transitions in vertebrate history.

Viromics unveils extraordinary genetic diversity of the family Closteroviridae in wild citrus.

Our knowledge of citrus viruses is largely skewed toward virus pathology in cultivated orchards. Little is known about the virus diversity in wild citrus species. Here, we used a metatranscriptomics approach to characterize the virus diversity in a wild citrus habitat within the proposed center of the origin of citrus plants. We discovered a total of 44 virus isolates that could be classified into species Citrus tristeza virus and putative species citrus associated ampelovirus 1, citrus associated ampelovirus 2, and citrus virus B within the family Closteroviridae, providing important information to explore the factors facilitating outbreaks of citrus viruses and the evolutionary history of the family Closteroviridae. We found that frequent horizontal gene transfer, gene duplication, and alteration of expression strategy have shaped the genome complexity and diversification of the family Closteroviridae. Recombination frequently occurred among distinct Closteroviridae members, thereby facilitating the evolution of Closteroviridae. Given the potential emergence of similar wild-citrus-originated novel viruses as pathogens, the need for surveillance of their pathogenic and epidemiological characteristics is of utmost priority for global citrus production.

Flourishing in water: the early evolution and diversification of plant receptor-like kinases.

Receptor-like kinases (RLKs) play significant roles in mediating innate immunity and development of plants. The evolution of plant RLKs has been characterized by extensive variation in copy numbers and domain configurations. However, much remains unknown about the origin, evolution, and early diversification of plant RLKs. Here, we perform phylogenomic analyses of RLKs across plants (Archaeplastida), including embryophytes, charophytes, chlorophytes, prasinodermophytes, glaucophytes, and rhodophytes. We identify the presence of RLKs in all the streptophytes (land plants and charophytes), nine out of 18 chlorophytes, one prasinodermophyte, and one glaucophyte, but not in rhodophytes. Interestingly, the copy number of RLKs increased drastically in streptophytes after the split of the clade of Mesostigmatophyceae and Chlorokybophyceae and other streptophytes. Moreover, phylogenetic analyses suggest RLKs from charophytes form diverse distinct clusters, and are dispersed along the diversity of land plant RLKs, indicating that RLKs have extensively diversified in charophytes and charophyte RLKs seeded the major diversity of land plant RLKs. We identify at least 81 and 76 different kinase-associated domains for charophyte and land plant RLKs, 23 of which are shared, suggesting that RLKs might have evolved in a modular fashion through frequent domain gains or losses. We also detect signatures of positive selection for many charophyte RLK groups, indicating potential functions in host-microbe interaction. Taken together, our findings provide significant insights into the early evolution and diversification of plant RLKs and the ancient evolution of plant-microbe symbiosis.

A Sister Lineage of Sampled Retroviruses Corroborates the Complex Evolution of Retroviruses.

The origin and deep history of retroviruses remain mysterious and contentious, largely because the diversity of retroviruses is incompletely understood. Here, we report the discovery of lokiretroviruses, a novel major lineage of retroviruses, within the genomes of a wide range of vertebrates (at least 137 species), including lampreys, ray-finned fishes, lobe-finned fishes, amphibians, and reptiles. Lokiretroviruses share a similar genome architecture with known retroviruses, but display some unique features. Interestingly, lokiretrovirus Env proteins share detectable similarity with fusion glycoproteins of viruses within the Mononegavirales order, blurring the boundary between retroviruses and negative sense single-stranded RNA viruses. Phylogenetic analyses based on reverse transcriptase demonstrate that lokiretroviruses are sister to all the retroviruses sampled to date, providing a crucial nexus for studying the deep history of retroviruses. Comparing congruence between host and virus phylogenies suggests lokiretroviruses mainly underwent cross-species transmission. Moreover, we find that retroviruses replaced their ribonuclease H and integrase domains multiple times during their evolutionary course, revealing the importance of domain shuffling in the evolution of retroviruses. Overall, our findings greatly expand our views of the diversity of retroviruses, and provide novel insights into the origin and complex evolutionary history of retroviruses.

Unearthing LTR Retrotransposon gag Genes Co-opted in the Deep Evolution of Eukaryotes.

LTR retrotransposons comprise a major component of the genomes of eukaryotes. On occasion, retrotransposon genes can be recruited by their hosts for diverse functions, a process formally referred to as co-option. However, a comprehensive picture of LTR retrotransposon gag gene co-option in eukaryotes is still lacking, with several documented cases exclusively involving Ty3/Gypsy retrotransposons in animals. Here, we use a phylogenomic approach to systemically unearth co-option of retrotransposon gag genes above the family level of taxonomy in 2,011 eukaryotes, namely co-option occurring during the deep evolution of eukaryotes. We identify a total of 14 independent gag gene co-option events across more than 740 eukaryote families, eight of which have not been reported previously. Among these retrotransposon gag gene co-option events, nine, four, and one involve gag genes of Ty3/Gypsy, Ty1/Copia, and Bel-Pao retrotransposons, respectively. Seven, four, and three co-option events occurred in animals, plants, and fungi, respectively. Interestingly, two co-option events took place in the early evolution of angiosperms. Both selective pressure and gene expression analyses further support that these co-opted gag genes might perform diverse cellular functions in their hosts, and several co-opted gag genes might be subject to positive selection. Taken together, our results provide a comprehensive picture of LTR retrotransposon gag gene co-option events that occurred during the deep evolution of eukaryotes and suggest paucity of LTR retrotransposon gag gene co-option during the deep evolution of eukaryotes.

Pervasive Positive Selection on Virus Receptors Driven by Host-Virus Conflicts in Mammals.

Viruses hijack cellular proteins, known as viral receptors, to initiate their infections. Viral receptors are subject to two conflicting directional forces, namely, negative selection to maintain their cellular function and positive selection resulted from the ever-changing host-virus arms race. Much remains unclear about how viral receptors evolved in mammals and whether viral receptors from different mammal groups experienced different strengths of natural selection. Here, we perform evolutionary analyses of 92 viral receptors in five major orders of mammals, including Carnivora, Cetartiodactyla, Chiroptera, Primates, and Rodentia. In all five mammal orders, signals of positive selection are detected for a high proportion of viral receptors (from 41% in Carnivora to 65% in Rodentia). Many positively selected residues overlap the host-virus interaction interface. Compared with control genes, we find viral receptors underwent elevated rates of adaptive evolution in all five mammal orders, suggesting that host-virus conflicts are the main driver of the adaptive evolution of viral receptors in mammals. Interestingly, the overall strength of natural selection acting on viral receptors driven by the host-virus arms race is largely homogenous and correlated among different mammal orders, with bats and rodents, zoonosis reservoirs of importance, being unexceptional. Taken together, our findings indicate host-virus conflicts have driven the elevated rate of adaptive evolution in viral receptors across mammals and might have important implications in zoonosis surveillance and prediction. IMPORTANCE Viral receptors are cellular proteins hijacked by viruses to help their infections. A complete picture on the evolution of viral receptors in mammals is still lacking. Here, we perform a comprehensive evolutionary analysis of the evolution of 92 viral receptors in five mammal orders, including Carnivora, Cetartiodactyla, Chiroptera, Primates, and Rodentia. We find that positive selection pervasively occurred during the evolution of viral receptors, and viral receptors exhibit an elevated rate of adaptive evolution compared to that of control genes in all five mammal orders, suggesting host-virus conflicts are a major driver of the adaptive evolution of viral receptors. Interestingly, the strength of positive selection acting on viral receptors is similar among the five mammal orders. Our study might have important implications in understanding the evolution of host-virus interaction.

A unique feature of swine ANP32A provides susceptibility to avian influenza virus infection in pigs.

Both the replication and transcription of the influenza virus are catalyzed by the viral polymerase complex. The polymerases of most avian influenza A viruses have poor performance in mammalian cells, which is considered to be one of the important species barriers. Pigs have been long considered as important intermediate hosts for interspecies transmission of the avian influenza virus, because of their susceptibility to infection with both avian and mammalian influenza viruses. However, the molecular basis of influenza polymerase adaptation in pigs remains largely unknown. ANP32A and ANP32B proteins have been identified as playing fundamental roles in influenza virus replication and host range determination. In this study, we found that swine ANP32A (swANP32A), unlike swine ANP32B or other mammalian ANP32A or B, shows stronger supporting activity to avian viral polymerase. Knockout of ANP32A in pig cells PK15 dramatically reduced avian influenza polymerase activity and viral infectivity, suggesting a unique feature of swANP32A in supporting avian influenza viral polymerase. This species-specific activity is mapped to two key sites, 106V and 156S, in swANP32A. Interestingly, the amino acid 106V is unique to pigs among all the vertebrate species studied, and when combined with 156S, exhibits positive epistasis in pigs. Mutation of 106V and 156S to the signature found in ANP32As from other mammalian species weakened the interaction between swANP32A and chicken viral polymerase, and reduced polymerase activity. Understanding the molecular basis of ANP32 proteins may help to discover new antiviral targets and design avian influenza resistant genome edited pigs.

Frequent Retroviral Gene Co-option during the Evolution of Vertebrates.

Endogenous retroviruses are ubiquitous in the vertebrate genomes. On occasion, hosts recruited retroviral genes to mediate their own biological functions, a process formally known as co-option or exaptation. Much remains unknown about the extent of retroviral gene co-option in vertebrates, although more than ten retroviral gene co-option events have been documented. Here, we use a phylogenomic approach to analyze more than 700 vertebrate genomes to uncover retroviral gene co-option taking place during the evolution of vertebrates. We identify a total of 177 independent retroviral gene co-option events in vertebrates, a majority of which have not been reported previously. Among these retroviral gene co-option events, 93 and 84 involve gag and env genes, respectively. More than 78.0% (138 out of 177) of retroviral gene co-option occurred within mammals. The gag and env co-option events share a generally similar temporal pattern with less frequent retroviral gene co-option identified in the deep branches, suggesting that retroviral gene co-option might have not been maintained for very long time periods. Moreover, we find co-opted retroviral genes are subject to different selection pressure, implying potentially diverse cellular functionality. Our study provides a comprehensive picture of co-opted retroviral genes during the evolution of vertebrates and has implications in understanding the ancient evolution of vertebrate-retrovirus interaction.

Genomic Epidemiology, Evolution, and Transmission Dynamics of Porcine Deltacoronavirus.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown once again that coronavirus (CoV) in animals are potential sources for epidemics in humans. Porcine deltacoronavirus (PDCoV) is an emerging enteropathogen of swine with a worldwide distribution. Here, we implemented and described an approach to analyze the epidemiology of PDCoV following its emergence in the pig population. We performed an integrated analysis of full genome sequence data from 21 newly sequenced viruses, along with comprehensive epidemiological surveillance data collected globally over the last 15 years. We found four distinct phylogenetic lineages of PDCoV, which differ in their geographic circulation patterns. Interestingly, we identified more frequent intra- and interlineage recombination and higher virus genetic diversity in the Chinese lineages compared with the USA lineage where pigs are raised in different farming systems and ecological environments. Most recombination breakpoints are located in the ORF1ab gene rather than in genes encoding structural proteins. We also identified five amino acids under positive selection in the spike protein suggesting a role for adaptive evolution. According to structural mapping, three positively selected sites are located in the N-terminal domain of the S1 subunit, which is the most likely involved in binding to a carbohydrate receptor, whereas the other two are located in or near the fusion peptide of the S2 subunit and thus might affect membrane fusion. Finally, our phylogeographic investigations highlighted notable South-North transmission as well as frequent long-distance dispersal events in China that could implicate human-mediated transmission. Our findings provide new insights into the evolution and dispersal of PDCoV that contribute to our understanding of the critical factors involved in CoVs emergence.

Host-Virus Arms Races Drive Elevated Adaptive Evolution in Viral Receptors.

Viral receptors are the cell surface proteins that are hijacked by viruses to initialize their infections. Viral receptors are subject to two conflicting directional forces, namely, negative selection due to functional constraints and positive selection due to host-virus arms races. It remains largely obscure whether negative pleiotropy limits the rate of adaptation in viral receptors. Here, we perform evolutionary analyses of 96 viral receptor genes in primates and find that 41 out of 96 viral receptors experienced adaptive evolution. Many positively selected residues in viral receptors are located at the virus-receptor interfaces. Compared with control proteins, viral receptors exhibit significantly elevated rate of adaptation. Further analyses of genetic polymorphisms in human populations reveal signals of positive selection and balancing selection for 53 and 5 viral receptors, respectively. Moreover, we find that 49 viral receptors experienced different selection pressures in different human populations, indicating that viruses represent an important driver of local adaptation in humans. Our findings suggest that diverse viruses, many of which have not been known to infect nonhuman primates, have maintained antagonistic associations with primates for millions of years, and the host-virus conflicts drive accelerated adaptive evolution in viral receptors.IMPORTANCE Viruses hijack cellular proteins, termed viral receptors, to assist their entry into host cells. While viral receptors experience negative selection to maintain their normal functions, they also undergo positive selection due to an everlasting evolutionary arms race between viruses and hosts. A complete picture on how viral receptors evolve under two conflicting forces is still lacking. In this study, we systematically analyzed the evolution of 96 viral receptors in primates and human populations. We found around half of viral receptors underwent adaptive evolution and exhibit significantly elevated rates of adaptation compared to control genes in primates. We also found signals of past natural selection for 58 viral receptors in human populations. Interestingly, 49 viral receptors experienced different selection pressures in different human populations, indicating that viruses represent an important driver of local adaptation in humans. Our results suggest that host-virus arms races drive accelerated adaptive evolution in viral receptors.

Convergent Co-option of the Retroviral gag Gene during the Early Evolution of Mammals.

Endogenous retroviruses, records of past retroviral infections, are ubiquitous in vertebrate genomes. On occasion, vertebrate hosts have co-opted retroviral genes for their own biological functions. Here, we perform a phylogenomic survey of retroviral gag gene homologs within vertebrate genomes and identify two ancient co-opted retroviral gag genes, designated wucaishi1 (wcs1) and wucaishi2 (wcs2), in mammals. Conserved synteny and evolutionary analyses suggest that the wcs1 and wcs2 co-options occurred before the origin of modern placental mammals (∼100 million years ago) and before the origin of modern marsupials (∼80 million years ago), respectively. We found that the wcs genes were lost or pseudogenized multiple times during the evolutionary course of mammals. While the wcs1 gene is mainly subject to negative selection in placental mammals (except in Perissodactyla), the wcs2 gene underwent positive selection in marsupials. Moreover, analyses of transcriptome-sequencing (RNA-seq) data suggest that the wcs1 and the wcs2 genes are expressed in a wide range of tissues. The convergent wcs co-option in mammals implies the retroviral gag gene might have been repurposed more frequently than previously thought.IMPORTANCE Retroviruses occasionally can infect host germ lines, forming endogenous retroviruses. Vertebrates, in turn, recruited retroviral genes for their own biological functions, a process formally known as co-option or exaptation. To date, co-opted retroviral gag genes have rarely been reported. In this study, we identified two co-opted retroviral gag genes, designated wucaishi1 (wcs1) and wucaishi2 (wcs2), in mammals. The co-option of wcs1 and wcs2 occurred before the origin of modern placentals and before the origin of modern marsupials, respectively. Our study indicates that retroviral gag gene co-option might have occurred more frequently than previously thought during the evolutionary course of vertebrates.

Endogenous retroviruses of non-avian/mammalian vertebrates illuminate diversity and deep history of retroviruses.

The deep history and early diversification of retroviruses remains elusive, largely because few retroviruses have been characterized in vertebrates other than mammals and birds. Endogenous retroviruses (ERVs) documented past retroviral infections and thus provide 'molecular fossils' for studying the deep history of retroviruses. Here we perform a comprehensive phylogenomic analysis of ERVs within the genomes of 92 non-avian/mammalian vertebrates, including 72 fishes, 4 amphibians, and 16 reptiles. We find that ERVs are present in all the genomes of jawed vertebrates, revealing the ubiquitous presence of ERVs in jawed vertebrates. We identify a total of >8,000 ERVs and reconstruct ~450 complete or partial ERV genomes, which dramatically expands the phylogenetic diversity of retroviruses and suggests that the diversity of exogenous retroviruses might be much underestimated in non-avian/mammalian vertebrates. Phylogenetic analyses show that retroviruses cluster into five major groups with different host distributions, providing important insights into the classification and diversification of retroviruses. Moreover, we find retroviruses mainly underwent frequent host switches in non-avian/mammalian vertebrates, with exception of spumavirus-related viruses that codiverged with their ray-finned fish hosts. Interestingly, ray-finned fishes and turtles appear to serve as unappreciated hubs for the transmission of retroviruses. Finally, we find retroviruses underwent many independent water-land transmissions, indicating the water-land interface is not a strict barrier for retrovirus transmission. Our analyses provide unprecedented insights into and valuable resources for studying the diversification, key evolutionary transitions, and macroevolution of retroviruses.

A synchronized global sweep of the internal genes of modern avian influenza virus.

Zoonotic infectious diseases such as influenza continue to pose a grave threat to human health. However, the factors that mediate the emergence of RNA viruses such as influenza A virus (IAV) are still incompletely understood. Phylogenetic inference is crucial to reconstructing the origins and tracing the flow of IAV within and between hosts. Here we show that explicitly allowing IAV host lineages to have independent rates of molecular evolution is necessary for reliable phylogenetic inference of IAV and that methods that do not do so, including 'relaxed' molecular clock models, can be positively misleading. A phylogenomic analysis using a host-specific local clock model recovers extremely consistent evolutionary histories across all genomic segments and demonstrates that the equine H7N7 lineage is a sister clade to strains from birds--as well as those from humans, swine and the equine H3N8 lineage--sharing an ancestor with them in the mid to late 1800s. Moreover, major western and eastern hemisphere avian influenza lineages inferred for each gene coalesce in the late 1800s. On the basis of these phylogenies and the synchrony of these key nodes, we infer that the internal genes of avian influenza virus (AIV) underwent a global selective sweep beginning in the late 1800s, a process that continued throughout the twentieth century and up to the present. The resulting western hemispheric AIV lineage subsequently contributed most of the genomic segments to the 1918 pandemic virus and, independently, the 1963 equine H3N8 panzootic lineage. This approach provides a clear resolution of evolutionary patterns and processes in IAV, including the flow of viral genes and genomes within and between host lineages.

Interspecies Transmission, Genetic Diversity, and Evolutionary Dynamics of Pseudorabies Virus.

BACKGROUND: Pseudorabies virus (PRV) causes Aujeszky's disease in pigs and can be transmitted to other mammals, including humans. In the current study, we systematically studied the interspecies transmission and evolutionary history of PRV. METHODS: We performed comprehensive analysis on the phylodynamics, selection, and structural biology to summarize the phylogenetic and adaptive evolution of PRV based on all available full-length and major glycoprotein sequences. RESULTS: PRV can be divided into 2 main clades with frequent interclade and intraclade recombination. Clade 2.2 (variant PRV) is currently the most prevalent genotype worldwide, and most commonly involved in cross-species transmission events (including humans). We also found that the population size of clade 2.2 has increased since 2011, and the effective reproduction number was >1 from 2011 to 2016, indicating that PRV may be still circulating in swine herds and is still a risk in relation with cross-species transmission in China. Of note, we identified amino acid sites in some important glycoproteins gB, gC, gD, and gE that may be associated with PRV adaptation to new hosts and immune escape to vaccines. CONCLUSIONS: Our study provides important genetic insight into the interspecies transmission and evolution of PRV within and between different hosts that warrant additional surveillance.

Insect Retroelements Provide Novel Insights into the Origin of Hepatitis B Viruses.

The origin of hepadnaviruses (Hepadnaviridae), a group of reverse-transcribing DNA viruses that infect vertebrates, remains mysterious. All the known retrotransposons are only distantly related to hepadnaviruses. Here, we report the discovery of two novel lineages of retroelements, which we designate hepadnavirus-like retroelement (HEART1 and HEART2), within the insect genomes through screening 1, 095 eukaryotic genomes. Both phylogenetic and similarity analyses suggest that the HEART retroelements represent the closest nonviral relatives of hepadnaviruses so far. The discovery of HEART retroelements narrows down the evolutionary gap between hepadnaviruses and retrotransposons and might thus provide unique insights into the origin and evolution of hepadnaviruses.