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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread globally, and scientists around the world are currently studying the virus intensively in order to fight against the on-going pandemic of the virus. To do so, SARS-CoV-2 is typically grown in the lab to generate viral stocks for various kinds of experimental investigations. However, accumulating evidence suggests that such viruses often undergo cell culture adaptation. Here, we systematically explored cell culture adaptation of two SARS-CoV-2 variants, namely the B.1.36.16 variant and the AY.30 variant, a sub lineage of the B.1.617.2 (Delta) variant, propagated in three different cell lines, including Vero E6, Vero E6/TMPRSS2, and Calu-3 cells. Our analyses detected numerous potential cell culture adaptation changes scattering across the entire virus genome, many of which could be found in naturally circulating isolates. Notable ones included mutations around the spike glycoprotein's multibasic cleavage site, and the Omicron-defining H655Y mutation on the spike glycoprotein, as well as mutations in the nucleocapsid protein's linker region, all of which were found to be Vero E6-specific. Our analyses also identified deletion mutations on the non-structural protein 1 and membrane glycoprotein as potential Calu-3-specific adaptation changes. S848C mutation on the non-structural protein 3, located to the protein's papain-like protease domain, was also identified as a potential adaptation change, found in viruses propagated in all three cell lines. Our results highlight SARS-CoV-2 high adaptability, emphasize the need to deep-sequence cultured viral samples when used in intricate and sensitive biological experiments, and illustrate the power of experimental evolutionary study in shedding lights on the virus evolutionary landscape.

Tuberculosis is a global public health problem with emergence of multidrug-resistant infections. Previous epidemiological studies of tuberculosis in Thailand have identified a clonal outbreak multidrug-resistant strain of Mycobacterium tuberculosis in the Kanchanaburi province, designated “MKR superspreader”, and this particular strain later was found to also spread to other regions. In this study, we elucidated its biology through RNA-Seq analyses and identified a set of genes involved in cholesterol degradation to be up-regulated in the MKR during the macrophage cell infection, but not in the H37Rv reference strain. We also found that the bacterium up-regulated genes associated with the ESX-1 secretion system during its intracellular growth phase, while the H37Rv did not. All results were confirmed by qRT-PCR. Moreover, we showed that compounds previously shown to inhibit the mycobacterial ESX-1 secretion system and cholesterol utilisation, and FDA-approved drugs known to interfere with the host cholesterol transportation were able to decrease the intracellular survival of the MKR when compared to the untreated control, while not that of the H37Rv. Altogether, our findings suggested that such pathways are important for the MKR’s intracellular growth, and potentially could be targets for the discovery of new drugs against this emerging multidrug-resistant strain of M. tuberculosis.

Tilapia lake virus (TiLV) is an emerging virus that is rapidly spreading across the world. Over the past 6 years (2014-2020), TiLV outbreaks had been reported in at least 16 countries, spanning three continents, including Asia, Africa, and America. Despite its enormous economic impact, its origin, evolution and epidemiology are still largely poorly characterized. Here, we report eight TiLV whole-genome sequences from Thailand sampled between 2014 and 2019. Together with publicly available sequences from various regions of the world, we estimated the origin of TiLV to be between 2003 and 2009, 5-10 years before the first report of the virus in Israel in 2014. Our analyses consistently showed that TiLV started to spread in 2000s, and reached its peak in 2014-2016, matching well with the timing of its first report. From 2016 onwards, the global TiLV population declined steadily. This could be a result of herd immunity building up in the fish population, and/or a reflection of a better awareness of the virus coupled with a better and more cautious protocol of Tilapia importation. Despite the fact that we included all publicly available sequences, our analyses revealed long unsampled histories of TiLVs in many countries, especially towards its basal diversification. This result highlights the lack and the need for systematic surveillance of TiLV in fish.

In this study, we performed genome-wide association analyses on SARS-CoV-2 genomes to identify genetic mutations associated with pre-symptomatic/asymptomatic COVID-19 cases. Various potential covariates and confounding factors of COVID-19 severity, including patient age, gender and country, as well as virus phylogenetic relatedness were adjusted for. In total, 3021 full-length genomes of SARS-CoV-2 generated from original clinical samples and whose patient status could be determined conclusively as either ‘pre-symptomatic/asymptomatic’ or ‘symptomatic’ were retrieved from the GISAID database. We found that the mutation 11 083G>T, located in the coding region of non-structural protein 6, is significantly associated with asymptomatic COVID-19. Patient age is positively correlated with symptomatic infection, while gender is not significantly correlated with the development of the disease. We also found that the effects of the mutation, patient age and gender do not vary significantly among countries, although each country appears to have varying baseline chances of COVID-19 symptom development.

Streptococcus agalactiae, also known as Lancefield Group BStreptococcus(GBS), is typically regarded as a neonatal pathogen; however, several studies have shown that the bacteria are capable of causing invasive diseases in non-pregnant adults as well. The majority of documented cases were from Southeast Asian countries, and the most common genotype found was ST283, which is also known to be able to infect fish. This study sequenced 12 GBS ST283 samples collected from adult patients in Thailand. Together with publicly available sequences, we performed temporo-spatial analysis and estimated population dynamics of the bacteria. Putative drug resistance genes were also identified and characterized, and the drug resistance phenotypes were validated experimentally. The results, together with historical records, draw a detailed picture of the past transmission history of GBS ST283 in Southeast Asia.

Tailed bacteriophages are the most abundant and diverse viruses in the world, with genome sizes ranging from 10 kbp to over 500 kbp. Yet, due to historical reasons, all this diversity is confined to a single virus order—Caudovirales, composed of just four families: Myoviridae, Siphoviridae, Podoviridae, and the newly created Ackermannviridae family. In recent years, this morphology-based classification scheme has started to crumble under the constant flood of phage sequences, revealing that tailed phages are even more genetically diverse than once thought. This prompted us, the Bacterial and Archaeal Viruses Subcommittee of the International Committee on Taxonomy of Viruses (ICTV), to consider overall reorganization of phage taxonomy. In this study, we used a wide range of complementary methods—including comparative genomics, core genome analysis, and marker gene phylogenetics—to show that the group of Bacillus phage SPO1-related viruses previously classified into the Spounavirinae subfamily, is clearly distinct from other members of the family Myoviridae and its diversity deserves the rank of an autonomous family. Thus, we removed this group from the Myoviridae family and created the family Herelleviridae—a new taxon of the same rank. In the process of the taxon evaluation, we explored the feasibility of different demarcation criteria and critically evaluated the usefulness of our methods for phage classification. The convergence of results, drawing a consistent and comprehensive picture of a new family with associated subfamilies, regardless of method, demonstrates that the tools applied here are particularly useful in phage taxonomy. We are convinced that creation of this novel family is a crucial milestone toward much-needed reclassification in the Caudovirales order., Systematic Biology, 69 (1), ISSN:1063-5157, ISSN:1076-836X

Recent surges in SARS-CoV-2 variants of concern (VOCs) call for the need to evaluate levels of vaccine-and infection-induced SARS-CoV-2 neutralizing antibodies (NAbs). CoronaVac (Sinovac Biotech, Beijing, China) is currently being used for mass vaccination in Thailand as well as other low-income countries. Three VOCs currently circulating within Thailand include the B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta) strains. We assessed NAb potency against the prototypic strain containing the original spike sequence (WT) compared to that against the 3 VOCs using sera derived from a cohort of healthcare workers who received a full 2-dose regimen of CoronaVac. Sera from two other cohorts consisting of COVID-19 patients who had been hospitalized in 2020 and 2021 were evaluated for comparison. We found that, despite equally robust production of S1-RBD-binding IgG and 100% seropositivity, sera from both CoronaVac vaccinees and naturally infected individuals had significantly reduced neutralizing capacity against all 3 VOCs compared to WT. Strikingly, NAb titers against Alpha and Beta were comparable, but Delta appears to be significantly more refractory to NAbs in all groups. Our results may help inform on CoronaVac NAb-inducing capacity, which is a proxy for vaccine efficacy, in the context of the WT strain and 3 VOCs. Our results also have critical implications for public health decision-makers who may need to maintain efficient mitigation strategies amid a potentially high risk for infection with VOCs even in those who have been previously infected.

The archaeal tailed viruses (arTV), evolutionarily related to tailed double-stranded DNA bacteriophages of the class Caudoviricetes, represent the most common isolates infecting halophilic archaea. Only a handful of these viruses have been genomically characterized, limiting our appreciation of their ecological impacts and evolution. Here, we present 37 new genomes of haloarchaeal tailed virus isolates, more than doubling the current number of sequenced arTVs. Analysis of all 63 available complete genomes of arTVs, which we propose to classify into 14 new families, suggests ancient divergence of archaeal and bacterial tailed viruses and points to an extensive sharing of genes involved in DNA metabolism and counter defense mechanisms, illuminating common strategies of virus-host interactions with tailed bacteriophages. Coupling of the comparative genomics with the host range analysis on a broad panel of haloarchaeal species uncovered four distinct groups of viral tail fiber adhesins controlling the host range expansion. The survey of metagenomes using viral hallmark genes suggests that the global architecture of the arTV community is shaped through recurrent transfers between different biomes, including hypersaline, marine and anoxic environments.

In this study, we compiled 84-year worth (1934–2017) of genomic and epidemiological data of foot-and-mouth disease virus (FMDV), and performed comprehensive analyses to determine its early origin and transmission route. We found that recombination is a key feature of FMDV, and that the genomic regions coding for structural and non-structural proteins have markedly different evolutionary histories, and evolve at different rates. Despite all of these differences, analyses of both structural and non-structural protein coding regions consistently suggested that the most recent common ancestor of FMDV could be dated back to the Middle Age, ~ 200 to 300 years earlier than previously thought. The ancestors of the Euro-Asiatic and SAT strains could be dated back to the mid-seventeenth century, and to the mid-fifteenth to mid-sixteenth century, respectively. Our results implicated Mediterranean counties as an early geographical origin of FMDV before spreading to Europe and subsequently to Asia and South America.

Herein, we performed a genome-wide association study on SARS-CoV-2 genomes to identify genetic variations that might be associated with the COVID-19 severity. 152 full-length genomes of SARS-CoV-2 that were generated from original clinical samples and whose patient status could be determined conclusively as either “asymptomatic” or “symptomatic” were retrieved from the GISAID database. We found that nucleotide variations at the genomic position 11,083, locating in the coding region of non-structural protein 6, were associated with the COVID-19 severity. While the 11083G variant (i.e. having G at the position 11,083) was more commonly found in symptomatic patients, the 11083T variant appeared to associate more often with asymptomatic infections. We also identified three microRNAs that differentially target the two variants, namely miR-485-3p, miR-539-3p, and miR-3149. This may in part contribute to the differential association of the two SARS-CoV-2 variants with the disease severity.

Recent discoveries of contemporary genotypes of hepatitis B virus and parvovirus B19 in ancient human remains demonstrate that little genetic change has occurred in these viruses over 4,500–6,000 years. Endogenous viral elements in host genomes provide separate evidence that viruses similar to many major contemporary groups circulated 100 million years ago or earlier. In this Opinion article, we argue that the extraordinary conservation of virus genome sequences is best explained by a niche-filling model in which fitness optimization is rapidly achieved in their specific hosts. Whereas short-term substitution rates reflect the accumulation of tolerated sequence changes within adapted genomes, longer-term rates increasingly resemble those of their hosts as the evolving niche moulds and effectively imprisons the virus in co-adapted virus–host relationships. Contrastingly, viruses that jump hosts undergo strong and stringent adaptive selection as they maximize their fit to their new niche. This adaptive capability may paradoxically create evolutionary stasis in long-term host relationships. While viruses can evolve and adapt rapidly, their hosts may ultimately shape their longer-term evolution., Studies of ancient DNA and endogenous viral elements have revealed extraordinary conservation of virus genome sequences over thousands or millions of years. In this Opinion article, Simmonds, Aiewsakun and Katzourakis describe a niche-filling model that describes how viruses can rapidly evolve to adapt to new host environments while their longer-term evolution is increasingly driven by their hosts.

High-throughput sequencing (HTS) and its use in recovering and assembling novel virus sequences from environmental, human clinical, veterinary and plant samples has unearthed a vast new catalogue of viruses. Their classification, known by their sequences alone, sets a major challenge to traditional virus taxonomy, especially at the family and species levels, which have been historically based largely on descriptive taxon definitions. These typically entail some knowledge of their phenotypic properties, including replication strategies, virion structure and clinical and epidemiological features, such as host range, geographical distribution and disease outcomes. Little to no information on these attributes is available, however, for viruses identified in metagenomic datasets. If such viruses are to be included in virus taxonomy, their assignments will have to be guided largely or entirely by metrics of genetic relatedness. The immediate problem here is that the International Committee on Taxonomy of Viruses (ICTV), an organisation that authorises the taxonomic classification of viruses, provides little or no guidance on how similar or how divergent viruses must be in order to be considered members of new species or new families. We have recently developed a method for scoring genomic (dis)similarity between viruses (Genome Relationships Applied to Virus Taxonomy - GRAViTy) among the eukaryotic and prokaryotic viruses currently classified by the ICTV. At the family and genus levels, we found large-scale consistency between genetic relationships and their taxonomic assignments for eukaryotic viruses of all genome configurations and genome sizes. Family assignments of prokaryotic viruses have, however, been made at a quite different genetic level, and groupings currently classified as sub-families are a much better match to the eukaryotic virus family level. These findings support the ongoing reorganisation of bacteriophage taxonomy by the ICTV Phage Study Group. A rapid and objective means to explore metagenomic viral diversity and make evidence-based assignments for such viruses at each taxonomic layer is essential. Analysis of sequences by GRAViTy provides evidence that family (and genus) assignments of currently classified viruses are largely underpinned by genomic relatedness, and these features could serve as a guide towards an evidence-based classification of metagenomic viruses in the future.

This study reports and characterises two novel distinct lineages of foamy viruses (FVs) in the forms of endogenous retroviruses (ERVs). Several closely related elements were found in the genome of oriental stork (Ciconia boyciana) and other was found in the genome of spine-bellied sea snake (Hydrophis hardwickii), designated ERV-Spuma.N-Cbo (where 'N' runs from one to thirteen) and ERV-Spuma.1-Hha, respectively. This discovery of avian and serpentine endogenous FVs adds snakes, and perhaps more crucially, birds to the list of currently known hosts of FVs, in addition to mammals, reptiles, amphibians, and fish. This indicates that FVs are, or at least were, capable of infecting all major lineages of vertebrates. Moreover, together with other FVs, phylogenetic analyses showed that both of them are most closely related to mammalian FVs. Further examination revealed that reptilian FVs form a deep paraphyletic group that is basal to mammalian and avian FVs, suggesting that there were multiple ancient FV cross-class transmissions among their hosts. Evolutionary timescales of various FV lineages were estimated in this study, in particular, the timescales of reptilian FVs and that of the clade of mammalian, avian, and serpentine FVs. This was accomplished by using the recently established time-dependent rate phenomenon models, inferred using mainly the knowledge of the co-speciation history between FVs and mammals. It was found that the estimated timescales matched very well with those of reptiles. Combined with the observed phylogenetic patterns, these results suggested that FVs likely co-speciated with ancient reptilian animals, but later jumped to a protomammal and/or a bird, which ultimately gave rise to mammalian and avian FVs. These results contribute to our understanding of FV emergence, specifically the emergence of mammalian and avian FVs, and provide new insights into how FVs co-evolved with their non-mammalian vertebrate hosts in the distant past.

Among all known retroviruses, foamy viruses (FVs) have the most stable virus–host co-speciation history, co-diverging in concert with their vertebrate hosts for hundreds of millions of years. However, detailed molecular analyses indicate that different parts of their genome might have different evolutionary histories. While their polymerase gene displays a robust and straightforward virus–host co-speciation pattern, the evolutionary history of their envelope (env) gene, is much more complicated. Here, we report eleven new FV env sequences in two mandrill populations in Central Africa, geographically separated by the Ogooué River into the North and the South populations. Phylogenetic reconstruction of the polymerase gene shows that the two virus populations are distinct, and each contains two variants of env genes co-existing with one another. The distinction between the two env variants can be mapped to the surface domain, flanked by two recombination hotspots, as previously reported for chimpanzee and gorilla FVs. Our analyses suggest that the two env variants originated during the diversification of Old World monkeys and apes, ∼30 million years ago. We also show that this env gene region forms two phylogenetically distinct clades, each displaying a host co-divergence and geographical separation pattern, while the rest of the genome of the two strains is phylogenetically indistinguishable in each of the host-specific groups. We propose possible evolutionary mechanisms to explain the modular nature of the FV genome.

Very little is known about the ancient origin of retroviruses, but owing to the discovery of their ancient endogenous viral counterparts, their early history is beginning to unfold. Here we report 36 lineages of basal amphibian and fish foamy-like endogenous retroviruses (FLERVs). Phylogenetic analyses reveal that ray-finned fish FLERVs exhibit an overall co-speciation pattern with their hosts, while amphibian FLERVs might not. We also observe several possible ancient viral cross-class transmissions, involving lobe-finned fish, shark and frog FLERVs. Sequence examination and analyses reveal two major lineages of ray-finned fish FLERVs, one of which had gained two novel accessory genes within their extraordinarily large genomes. Our phylogenetic analyses suggest that this major retroviral lineage, and therefore retroviruses as a whole, have an ancient marine origin and originated together with, if not before, their jawed vertebrate hosts >450 million years ago in the Ordovician period, early Palaeozoic Era., Endogenous retroviruses are viruses that have become integrated into the genomes of their hosts. Here, the authors investigate the evolution of foamy-like endogenous retroviruses, and, by taking into account the temporal dynamics of the rate of viral evolution, suggest that retroviruses arose at least 450 million years ago in marine vertebrates.

Among the most fundamental questions in viral evolutionary biology are how fast viruses evolve and how evolutionary rates differ among viruses and fluctuate through time. Traditionally, viruses are loosely classed into two groups: slow-evolving DNA viruses and fast-evolving RNA viruses. As viral evolutionary rate estimates become more available, it appears that the rates are negatively correlated with the measurement timescales and that the boundary between the rates of DNA and RNA viruses might not be as clear as previously thought. In this study, we collected 396 viral evolutionary rate estimates across almost all viral genome types and replication strategies, and we examined their rate dynamics. We showed that the time-dependent rate phenomenon exists across multiple levels of viral taxonomy, from the Baltimore classification viral groups to genera. We also showed that, by taking the rate decay dynamics into account, a clear division between the rates of DNA and RNA viruses as well as reverse-transcribing viruses could be recovered. Surprisingly, despite large differences in their biology, our analyses suggested that the rate decay speed is independent of viral types and thus might be useful for better estimation of the evolutionary time scale of any virus. To illustrate this, we used our model to reestimate the evolutionary timescales of extant lentiviruses, which were previously suggested to be very young by standard phylogenetic analyses. Our analyses suggested that these viruses are millions of years old, in agreement with paleovirological evidence, and therefore, for the first time, reconciled molecular analyses of ancient and extant viruses. IMPORTANCE This work provides direct evidence that viral evolutionary rate estimates decay with their measurement timescales and that the rate decay speeds do not differ significantly among viruses despite the vast differences in their molecular features. After adjustment for the rate decay dynamics, the division between the rates of double-stranded DNA (dsDNA), single-stranded RNA (ssRNA), and ssDNA/reverse-transcribing viruses could be seen more clearly than before. Our results provide a guideline for further improvement of the molecular clock. As a demonstration of this, we used our model to reestimate the timescales of modern lentiviruses, which were previously thought to be very young, and concluded that they are millions of years old. This result matches the estimate from paleovirological analyses, thus bridging the gap between ancient and extant viral evolutionary studies.

Genome Relationship Applied to Virus Taxonomy (GRAViTy) is a genetics-based tool that computes sequence relatedness between viruses. Composite generalized Jaccard (CGJ) distances combine measures of homology between encoded viral genes and similarities in genome organizational features (gene orders and orientations). This scoring framework effectively recapitulates the current, largely morphology and phenotypic-based, family-level classification of eukaryotic viruses. Eukaryotic virus families typically formed monophyletic groups with consistent CGJ distance cut-off dividing between and within family divergence ranges. In the current study, a parallel analysis of prokaryotic virus families revealed quite different sequence relationships, particularly those of tailed phage families (Siphoviridae, Myoviridae and Podoviridae), where members of the same family were generally far more divergent and often not detectably homologous to each other. Analysis of the 20 currently classified prokaryotic virus families indeed split them into 70 separate clusters of tailed phages genetically equivalent to family-level assignments of eukaryotic viruses. It further divided several bacterial (Sphaerolipoviridae, Tectiviridae) and archaeal (Lipothrixviridae) families. We also found that the subfamily-level groupings of tailed phages were generally more consistent with the family assignments of eukaryotic viruses, and this supports ongoing reclassifications, including Spounavirinae and Vi1virus taxa as new virus families. The current study applied a common benchmark with which to compare taxonomies of eukaryotic and prokaryotic viruses. The findings support the planned shift away from traditional morphology-based classifications of prokaryotic viruses towards a genome-based taxonomy. They demonstrate the feasibility of a unified taxonomy of viruses into which the vast body of metagenomic viral sequences may be consistently assigned. ispartof: JOURNAL OF GENERAL VIROLOGY vol:99 issue:9 pages:1331-1343 ispartof: location:England status: published

Table S4. Protein profile hidden Markov models responsible for inter-family relationships. List of PPHMMs that link together different virus families. (DOCX 23Â kb)

Analysis of GRAViTy groupings that conflict with ITCV family assignments. Analysis of sequences whose assignment by GRAViTy conflicts with their ICTV classification. (PDF 59Â kb)

Table S2. Summary of the virus taxa analysed in this study. Listing of ICTV assigned taxa of the sequences analysed in the study. (DOCX 17Â kb)

Background Although simian foamy viruses (SFV) are the only exogenous retroviruses to infect New World monkeys (NWMs), little is known about their evolutionary history and epidemiology. Previous reports show distinct SFVs among NWMs but were limited to small numbers of captive or wild monkeys from five (Cebus, Saimiri, Ateles, Alouatta, and Callithrix) of the 15 NWM genera. Other studies also used only PCR testing or serological assays with limited validation and may have missed infection in some species. We developed and validated new serological and PCR assays to determine the prevalence of SFV in blood specimens from a large number of captive NWMs in the US (n = 274) and in captive and wild-caught NWMs (n = 236) in Peruvian zoos, rescue centers, and illegal trade markets. Phylogenetic and co-speciation reconciliation analyses of new SFV polymerase (pol) and host mitochondrial cytochrome B sequences, were performed to infer SFV and host co-evolutionary histories. Results 124/274 (45.2 %) of NWMs captive in the US and 59/157 (37.5 %) of captive and wild-caught NWMs in Peru were SFV WB-positive representing 11 different genera (Alouatta, Aotus, Ateles, Cacajao, Callithrix, Cebus, Lagothrix, Leontopithecus, Pithecia, Saguinus and Saimiri). Seroprevalences were lower at rescue centers (10/53, 18.9 %) compared to zoos (46/97, 47.4 %) and illegal trade markets (3/7, 8/19, 42.9 %) in Peru. Analyses showed that the trees of NWM hosts and SFVs have remarkably similar topologies at the level of species and sub-populations suggestive of co-speciation. Phylogenetic reconciliation confirmed 12 co-speciation events (p

Background It appears that substitution rate estimates co-vary very strongly with their timescale of measurement; the shorter the timescale, the higher the estimated value. Foamy viruses have a long history of co-speciation with their hosts, and one of the lowest estimated rates of evolution among viruses. However, when their rate of evolution is estimated over short timescales, it is more reminiscent of the rapid rates seen in other RNA viruses. This discrepancy between their short-term and long-term rates could be explained by the time-dependency of substitution rate estimates. Several empirical models have been proposed and used to correct for the time-dependent rate phenomenon (TDRP), such as a vertically-translated exponential rate decay model and a power-law rate decay model. Nevertheless, at present, it is still unclear which model best describes the rate dynamics. Here, we use foamy viruses as a case study to empirically describe the phenomenon and to determine how to correct rate estimates for its effects. Four empirical models were investigated: (i) a vertically-translated exponential rate decay model, (ii) a simple exponential rate decay model, (iii) a vertically-translated power-law rate decay model, and (iv) a simple power-law rate decay model. Results Our results suggest that the TDRP is likely responsible for the large discrepancy observed in foamy virus short-term and long-term rate estimates, and the simple power-law rate decay model is the best model for inferring evolutionary timescales. Furthermore, we demonstrated that, within the Bayesian phylogenetic framework, currently available molecular clocks can severely bias evolutionary date estimates, indicating that they are inadequate for correcting for the TDRP. Our analyses also suggest that different viral lineages may have different TDRP dynamics, and this may bias date estimates if it is unaccounted for. Conclusions As evolutionary rate estimates are dependent on their measurement timescales, their values must be used and interpreted under the context of the timescale of rate estimation. Extrapolating rate estimates across large timescales for evolutionary inferences can severely bias the outcomes. Given that the TDRP is widespread in nature but has been noted only recently the estimated timescales of many viruses may need to be reconsidered and re-estimated. Our models could be used as a guideline to further improve current phylogenetic inference tools. Electronic supplementary material The online version of this article (doi:10.1186/s12862-015-0408-z) contains supplementary material, which is available to authorized users.

Additional file 2: Table S1. Three letter species codes used for New World monkeys samples in the study and used to label taxa in the phylogenetic analyses (Figs. 3, 4, and S1).

Following the recent availability of high-coverage genomes for Denisovan and Neanderthal hominids, we conducted a screen for endogenized retroviruses, identifying six novel, previously unreported HERV-K(HML2) elements (HERV-K is human endogenous retrovirus K). These elements are absent from the human genome (hg38) and appear to be unique to archaic hominids. These findings provide further evidence supporting the recent activity of the HERV-K(HML2) group, which has been implicated in human disease. They will also provide insights into the evolution of archaic hominids.

Background Foamy viruses (FVs) are a unique subfamily of retroviruses that are widely distributed in mammals. Owing to the availability of sequences from diverse mammals coupled with their pattern of codivergence with their hosts, FVs have one of the best-understood viral evolutionary histories ever documented, estimated to have an ancient origin. Nonetheless, our knowledge of some parts of FV evolution, notably that of prosimian and afrotherian FVs, is far from complete due to the lack of sequence data. Results Here, we report the complete genome of the first extant prosimian FV (PSFV) isolated from a lorisiforme galago (PSFVgal), and a novel partial endogenous viral element with high sequence similarity to FVs, present in the afrotherian Cape golden mole genome (ChrEFV). We also further characterize a previously discovered endogenous PSFV present in the aye-aye genome (PSFVaye). Using phylogenetic methods and available FV sequence data, we show a deep divergence and stable co-evolution of FVs in eutherian mammals over 100 million years. Nonetheless, we found that the evolutionary histories of bat, aye-aye, and New World monkey FVs conflict with the evolutionary histories of their hosts. By combining sequence analysis and biogeographical knowledge, we propose explanations for these mismatches in FV-host evolutionary history. Conclusion Our discovery of ChrEFV has expanded the FV host range to cover the whole eutherian clade, and our evolutionary analyses suggest a stable mammalian FV-host co-speciation pattern which extends as deep as the exafroplacentalian basal diversification. Nonetheless, two possible cases of host switching were observed. One was among New World monkey FVs, and the other involves PSFVaye and a bat FV which may involve cross-species transmission at the level of mammalian orders. Our results highlight the value of integrating multiple sources of information to elucidate the evolutionary history of viruses, including continental and geographical histories, ancestral host locations, in addition to the natural history of host and virus. Electronic supplementary material The online version of this article (doi:10.1186/1742-4690-11-61) contains supplementary material, which is available to authorized users.

The rapid rates of viral evolution allow us to reconstruct the recent history of viruses in great detail. This feature, however, also results in rapid erosion of evolutionary signal within viral molecular data, impeding studies of their deep history. Thus, the further back in time, the less accurate the inference becomes. Furthermore, reconstructing complex histories of transmission can be challenging, especially where extinct viral lineages are concerned. This problem has been partially solved by the discovery of viruses embedded in host genomes, known as endogenous viral elements (EVEs). Some of these endogenous viruses are derived from ancient relatives of extant viruses, allowing us to better examine ancient viral host range, geographical distribution and transmission routes. Moreover, our knowledge of viral evolutionary timescales and rate dynamics has also been greatly improved by their discovery, thereby bridging the gap between recent and ancient viral evolution.