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Frontiers in Microbiology
Evolutionary and Genomic Microbiology
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Thorsten Allers
University of Nottingham, United Kingdom
David L. Bernick
University of California, Santa Cruz, United States
David Paez-Espino
Joint Genome Institute, Lawrence Berkeley National Laboratory, United States
The editor and reviewers' affiliations are the latest provided on their Loop research profiles and may not reflect their situation at the time of review.
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Original Research ARTICLE
Front. Microbiol., 31 October 2017 | https://doi.org/10.3389/fmicb.2017.02110
Do Viruses Exchange Genes across Superkingdoms of Life?
Shahana S. Malik1†, Syeda Azem-e-Zahra1†, Kyung Mo Kim2, Gustavo Caetano-Anollés3 and Arshan Nasir1,3*
1Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan
2Division of Polar Life Sciences, Korea Polar Research Institute, Incheon, South Korea
3Evolutionary Bioinformatics Laboratory, Department of Crop Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, United States
Viruses can be classified into archaeoviruses, bacterioviruses, and eukaryoviruses according to the taxonomy of the infected host. The host-constrained perception of viruses implies preference of genetic exchange between viruses and cellular organisms of their host superkingdoms and viral origins from host cells either via escape or reduction. However, viruses frequently establish non-lytic interactions with organisms and endogenize into the genomes of bacterial endosymbionts that reside in eukaryotic cells. Such interactions create opportunities for genetic exchange between viruses and organisms of non-host superkingdoms. Here, we take an atypical approach to revisit virus-cell interactions by first identifying protein fold structures in the proteomes of archaeoviruses, bacterioviruses, and eukaryoviruses and second by tracing their spread in the proteomes of superkingdoms Archaea, Bacteria, and Eukarya. The exercise quantified protein structural homologies between viruses and organisms of their host and non-host superkingdoms and revealed likely candidates for virus-to-cell and cell-to-virus gene transfers. Unexpected lifestyle-driven genetic affiliations between bacterioviruses and Eukarya and eukaryoviruses and Bacteria were also predicted in addition to a large cohort of protein folds that were universally shared by viral and cellular proteomes and virus-specific protein folds not detected in cellular proteomes. These protein folds provide unique insights into viral origins and evolution that are generally difficult to recover with traditional sequence alignment-dependent evolutionary analyses owing to the fast mutation rates of viral gene sequences.
Depending on the nature of the infected host, viruses can be broadly classified into three major groups, archaeoviruses, bacterioviruses (Krupovic et al., 2016), and eukaryoviruses, in addition to the lesser-known virophages that parasitize giant viruses (La Scola et al., 2003, 2008). While host jumps are common (Longdon et al., 2014; Geoghegan et al., 2017), such as HIV from chimps (Sharp and Hahn, 2010), SARS Coronavirus from bats (Li et al., 2005), H1N1 from birds (Webby and Webster, 2001), and arboviruses that replicate in mammalian cells and insect vectors, viruses are not known to infect cellular organisms separated by superkingdom (domain of life) boundaries (Nasir et al., 2014, 2017). This has been confirmed by recent studies revealing strong biases in the distribution of viral replicon types in superkingdoms such as the paucity of discovered RNA and retrotranscribing viruses in prokaryotes and their abundance and diversity in eukaryotic species such as mammals and vertebrates (Nasir et al., 2014; Koonin et al., 2015). The highly specific nature of virus-host interactions logically constrains genetic exchange to occur more frequently between the interacting partners. For example, bacterioviruses are known to capture bacterial genes involved in toxins and photosynthesis (Canchaya et al., 2004; Lindell et al., 2004). Similarly, eukaryoviruses often capture genes involved in antiviral immunity from eukaryotic cells (Elde and Malik, 2009; Rappoport and Linial, 2012). Thus, host-constrained evolution of viral lineages has led to favoring either the "escape" or "reduction" models for the origin of modern viruses, both attributing viral origins from modern or ancient host cells (reviewed in Hendrix et al., 2000; Forterre and Krupovic, 2012; Nasir et al., 2012b).
Virus-host affiliations however are largely established by observing the cytopathic effects of viral infection or by microscopy detection of virion particles. These properties relate to the lytic mode of viral reproduction that has historically remained on focus due to the noxious effects that lysis has on human health, livestock, and agriculture. However, viruses can also frequently endogenize by integration into cellular genomes (Feschotte and Gilbert, 2012), sometimes providing useful novel genes to make them evolutionarily competitive (Cornelis et al., 2012). Moreover, many viruses either infect bacterial symbionts of eukaryotic cells (e.g., the bacterial component of the human microbiota, Turnbaugh et al., 2007) or reside as prophages in the genomes of obligate intracellular bacteria that infect a wide range of eukaryotic hosts (Brüssow et al., 2004). These virus-cell interactions are largely non-lytic in nature and because they do not yield the classic phenotypic effects of viral infection, have likely remained underestimated through established methods of virus discovery (reviewed in Nasir et al., 2017). Importantly, such interactions blur the traditional concept of "virus host" and raise the possibility of viruses interacting (not necessarily in a lytic manner) and exchanging genetic material simultaneously with more than one superkingdom of life. Bordenstein and Bordenstein (2016) recently reported an example of a eukaryotic gene module in bacteriophage WO residing as prophage in the intracellular α-proteobacterium Wolbachia, which infects a large group of insects. In order to produce viral progeny, the bacteriophage WO must neutralize antiviral defense and enter/exit the membranes of both bacterial and eukaryal organisms (Bordenstein and Bordenstein, 2016). The study therefore offered unique insights into virus-cell interactions that extend beyond their known hosts and identified viruses of endosymbiotic bacteria as interesting examples of vectors with genetic material from non-host superkingdoms.
Here we take a comparative genomic approach to revisit virus-cell interactions by identifying the repertoires of protein structural domains (proteomes) in 3,440 viruses categorized into archaeoviruses, bacterioviruses, and eukaryoviruses and tracing their spread in the proteomes of 1,620 "hosts" from Archaea, Bacteria, and Eukarya. Protein domains were grouped into fold superfamilies (FSFs), as defined by the structural classification of proteins (SCOP) database (Andreeva et al., 2008; Fox et al., 2014) to include distantly related domains that show negligible sequence identity (can be < 15%) but recognizable common three-dimensional (3D) cores and biochemical functions that are likely indicative of shared ancestry. The evolutionary conservation of FSFs makes them useful molecular characters for inferring long-term viral evolutionary patterns, especially since fast mutational rates of viral gene sequences (Sanjuán et al., 2010) sometimes prohibit meaningful global evolutionary analyses (Abroi and Gough, 2011; Caetano-Anollés and Nasir, 2012; Nasir and Caetano-Anollés, 2015).
The comparative exercise of tracing the spread of each viral FSF in cellular proteomes was made explicit with an f-value representing the fraction of cellular proteomes encoding individual FSFs (see Methods). The f-values of viral FSFs in cellular proteomes and their reported biochemical functions were then used to postulate hypotheses regarding the direction of gene transfer, virus-to-cell or cell-to-virus (see Figure 1 for demonstration). For example, an FSF with a viral hallmark function (e.g., virion synthesis) that had negligible presence in proteomes of a cellular superkingdom (e.g., f < 1%) was considered a candidate for horizontal gene transfer (HGT) event from virus-to-cell rather than from cell-to-virus as the latter would require invoking multiple gene loss events in related cellular species. This approach of inferring the likely direction of gene transfer is thus similar to considering anomalous phylogenetic distributions of genes in closely related species as more likely a result of HGT rather than vertical inheritance and loss. This method reliably detects HGT events (Philippe and Douady, 2003), especially in viral genes where sequence identity with cellular counterparts may be too low to produce meaningful alignment-dependent phylogenetic trees (Nasir and Caetano-Anollés, 2015). The tracings yielded unique insights into genetic transfers between viruses and cells, highlighted the quantitatively greater cross-superkingdom genetic exchange occurring between bacterioviruses and eukaryotes and eukaryoviruses and bacteria, and supported models of viral origins from ancient cells (Nasir et al., 2012b). The genetic crosstalk between viral and cellular proteomes that we uncover with this comparative genomics approach presents a more global picture for evolutionary understanding of virus-cell interactions that goes beyond the perceived textbook definitions of virus hosts (Nasir et al., 2017).
Figure 1. Demonstration of virus-to-cell and cell-to-virus HGT events. Ten genomes are displayed as colored closed disks each for Archaea (black), Bacteria (blue), Eukarya (green), and viruses. Seven out of 10 viral genomes encode different virus hallmark FSFs (with incidence represented by different shades of red) such as those involved in virion synthesis and capsid assembly. If any of these virus-hallmark FSFs is detected in no more than 1/10 cellular genomes (real f-values are even lower), the event is determined to be virus-to-cell HGT. In turn, any of the cellular FSFs that are widespread in cells (i.e., present in 9/10 cellular genomes) are detected in a viral genome, that event is determined to be cell-to-virus HGT.
A Large Number of Protein Folds Shared Exclusively between Viruses and Their Host Genomes Were Likely Transferred from Viruses to Cells
A total of 98, 441, and 489 FSFs were detected in the proteomes of 62 archaeoviruses, 1,223 bacterioviruses, and 2,155 eukaryoviruses (Table S1), respectively (Figure 2). Based on the presence/absence of these viral FSFs in 1,620 cellular proteomes from Archaea (122 in number), Bacteria (1,115), and Eukarya (383), seven mutually exclusive Venn groups could be defined each for archaeoviruses, bacterioviruses, and eukaryoviruses: A (viral FSFs shared only with archaeal proteomes), B (shared only with bacterial proteomes), E (shared only with eukaryotic proteomes), AB (shared only with prokaryotic proteomes), AE (shared only with archaeal and eukaryal proteomes), BE (shared only with bacterial and eukaryal proteomes), and ABE (shared with proteomes of all three superkingdoms), in addition to virus-specific (V) FSFs not detected in cellular proteomes (Figure 2).
Figure 2. Sharing of protein structural domains between viral and cellular proteomes. The Venn diagrams illustrate the number of FSFs detected in the proteomes of archaeoviruses, bacterioviruses, and eukaryoviruses and their distributions in the proteomes of superkingdoms Archaea (A), Bacteria (B), and Eukarya (E). n = total number of viral proteomes, m = total number of FSFs detected in viral proteomes. V represents virus-specific FSFs (Table 2).
Under the expected host-constrained evolution model of viral lineages, viruses of any superkingdom are expected to share more FSFs with organisms of their host superkingdom rather than with organisms of other superkingdoms. Indeed, archaeoviruses shared a single FSF exclusively with Archaea (Venn group A; Hypothetical protein D-63) but none exclusively with Bacteria (group B) and Eukarya (group E) (Figure 2, Table 1). In turn, bacterioviruses shared 29 FSFs exclusively with Bacteria (group B) but also 2 and 6 FSFs with Archaea and Eukarya in groups A and E, respectively. Similarly, eukaryoviruses shared 37 FSFs exclusively with Eukarya (group E) but also 1 and 5 FSFs with Archaea and Bacteria in groups A and B, respectively (Figure 2, Table 1). At first glance, the data support the idea that viruses tend to share/exchange more genes with their host groups relative to organisms they do not infect or associate with.
Table 1. Virus-Host FSF sharing.
Remarkably, the 29 FSFs shared exclusively between bacterioviral and bacterial proteomes included several viral hallmark proteins involved in phage (virus) assembly such as the gp9 and gp10 proteins, head-binding, head-to-tail joining, head decoration, and tail proteins, along with the major coat proteins of ssDNA harboring bacterioviruses (Inoviridae) and the dimerization domain of bacteriophage T4 recombination endonuclease VII (Table 1). In addition, the coiled-coiled domain of bacterial neurotoxin involved in host virulence was also detected. Interestingly, the majority of FSFs in group B had f-values close to 0 indicating their rare presence in bacterial proteomes (Table 1). Collectively, therefore, the enrichment of the B Venn group in viral hallmark functions with negligible presence in bacterial proteomes suggests that these genes were likely acquired by bacterial cells from viruses via virus-to-cell HGT, a phenomenon that has been assumed to be relatively less frequent than cell-to-virus HGT (Moreira and Lopez-Garcia, 2009), though now increasingly being revisited (Forterre, 2016). Similarly, viral hallmark proteins such as the viral capsid and coat-related proteins (e.g., the "jelly-roll" and "double jelly-roll" folds) (Abrescia et al., 2012), viral glycoproteins and matrix proteins, the integrase proteins of retroviruses and HIV, and toxins were part of the 37 FSFs shared exclusively between eukaryoviruses and Eukarya (the E Venn group) with low f-values in eukaryal proteomes (Table 1). These viral hallmark proteins shared exclusively between eukaryoviruses and eukaryotes could therefore also represent episodes of virus-to-cell gene transfer. In turn, other E FSFs such as the CCCH zinc finger domains (involved in regulation and DNA binding), CAD and PB1 domains (cell cycle and apoptosis), CRAL/TRIO domains (likely functional components of the visual cycle), TRAF-domain like (involved in stress response, immunity, apoptosis, among other roles), and others were near ubiquitous in eukaryotic proteomes (i.e., f-value close to 1.0, Table 1). These "cell-like" proteins detected in eukaryoviruses could therefore suggest recent gene capture by viruses from cells (i.e., cell-to-virus HGT) as likely part of viral mimicry of cellular proteins to interfere with the antiviral response (Elde and Malik, 2009).
In summary, a large number of FSFs shared exclusively between viruses and their host genomes had rare presence in hosts and were involved in virus-hallmark functions suggesting these genes likely originated in viral lineages and were later transferred to their host cells.
Traces of Genetic Crosstalk between Viruses and Non-host Superkingdoms Could Be Recovered from the Comparative Genomic Data
While the data of Figure 2 indicated significant levels of genetic exchange restricted between viruses and their known host superkingdoms, some bacterioviral and eukaryoviral FSFs were also shared with Eukarya and Bacteria, respectively (archaeoviruses shared no domains exclusively with either Bacteria or Eukarya) (Figure 2, Tables S2–S4). For example, bacterioviruses shared 2 FSFs exclusively with Archaea (group A) and 6 with Eukarya (group E) (Table S3). Interestingly, 4/6 E FSFs in bacterioviruses could be considered viral hallmark proteins such as FSFs b.121.2 (the "double jelly-roll" fold hallmark of capsid proteins of the PRD1/Adenovirus-like lineage) (Bamford, 2003; Abrescia et al., 2012), b.121.5 (the "jelly-roll" fold in ssDNA viruses members of the Picornavirus-like lineage), d.85.1 (capsid/coat related fold in RNA bacteriophages), and a.251.1 (the phage replication organizer domain) (Table S3). Viruses have been recently (re)-classified into structure-based lineages based on 3D structural similarities in capsid/coat architectures or common principles of functional virion construction (Bamford, 2003; Abrescia et al., 2012; Nasir and Caetano-Anollés, 2017). Some of the lineages such as the PRD1/Adenovirus-like lineage (characterized by the so-called "double jelly-roll" fold) include member viruses infecting the three cellular superkingdoms (Bamford, 2003; Abrescia et al., 2012). Thus, it is no surprise that bacterioviruses share capsid/coat related protein folds characteristic of eukaryoviruses. It is however indeed intriguing to note that these FSFs were present in eukaryotic proteomes, especially because the capsid is considered to be a virus hallmark (Benson et al., 2004; Abrescia et al., 2010). Thus, rare occurrences of capsid/coat related genes in cellular proteomes are more likely due to virus-to-cell HGT or their utilization in the assembly of capsid-like architectures in cells (e.g., carboxysomes and protein microcompartments in prokaryotes, Yeates et al., 2007, 2011) that are hitherto believed to be rare in cells (Cheng and Brooks, 2013; Nasir and Caetano-Anollés, 2017).
In turn, eukaryoviruses shared a single FSF exclusively with Archaea (group A; Chromosomal protein MC1) and 5 FSFs exclusively with Bacteria (group B) (Table S4). The MC1 protein is associated with thermophilic archaeal species (f-value = 0.26 in Archaea) and is involved in protecting DNA denaturation at high temperature (Chartier et al., 1989). Its presence in eukaryoviruses (but not in eukaryotic proteomes!) is therefore intriguing and could signal undiscovered viral-mediated interactions between eukaryotic and archaeal species. In turn, the 5 FSFs shared exclusively between eukaryoviruses and bacterial proteomes (the B Venn group) included capsid proteins (Outer capsid protein sigma 3) and other virus and cell-like proteins likely indicating a mixed ancestry (Table S4).
Finally, the BE Venn group for archaeoviruses, the AE group for bacterioviruses, and the AB group for eukaryoviruses may also represent genetic exchanges occurring between viruses and non-host superkingdoms. For archaeoviruses, the d.285.1 (DNA-binding domain of intron-encoded endonucleases), a.118.25 (TROVE domain-like), and b.22.1 (TNF-like) FSFs were detected in the BE group. In turn, only one bacterioviral FSF (d.282.1, SSo0622-like) was detected in the AE group and 2 eukaryoviral FSFs were detected in the AB group (a.18.1, T4 endonuclease V and g.90.1, E6 C-terminal domain-like) (highlighted in Tables S2–S4). These FSFs are likely candidates of genetic transfer occurring between viruses and non-host superkingdoms, more likely in the cell-to-virus direction because of the "cell-like" nature of these FSFs.
An Unanticipated Relatively Greater Genetic Affiliation between Bacterioviruses and Eukaryal Proteomes and Eukaryoviruses and Bacterial Proteomes
Bacterioviruses shared 66 FSFs and eukaryoviruses shared 65 FSFs with both Bacteria and Eukarya (the BE groups), respectively, which constituted 15 and 13% of total bacterioviral and eukaryoviral FSFs, respectively (Figure 2). Only 20 BE FSFs overlapped and the remaining (46/66 in bacterioviruses and 45/65 in eukaryoviruses) were uniquely shared with bacterial and eukaryal proteomes (Figure 3A), thus extending the total number of BE FSFs to 111. The 46 BE FSFs unique to bacterioviruses (i.e., FSFs detected in bacterioviral, bacterial and eukaryal proteomes but not in eukaryoviral proteomes) were significantly more widespread in bacterial proteomes (Welch two-sample t-test, P = 0.01) while the 45 BE FSFs unique to eukaryoviruses (FSFs detected in eukaryoviral, bacterial and eukaryal proteomes but not in bacterioviral proteomes) were significantly more widespread in eukaryotic proteomes (P < 0.0001) with f-values approaching 1.0 in some cases (Figure 3B).
Figure 3. The structural domain composition of the BE Venn group in bacterioviruses and eukaryoviruses. (A) The Venn diagram describes how the BE FSFs were shared between bacterioviruses and eukaryoviruses. (B) Boxplots display the distribution of f-values (number of proteomes in a superkingdom encoding an FSF divided by the total number of proteomes in that superkingdom) for BE FSFs unique to bacterioviruses, unique to eukaryoviruses, and common to both the bacterial and eukaryal proteomes (see also Table S5). P-values were calculated from two-sample Welch t-tests.
We hypothesize that bacterioviruses and eukaryoviruses acquired BE FSFs directly from their host cells (i.e., Bacteria and Eukarya, respectively) without the need to invoke genetic crosstalk between viruses and non-host superkingdoms and also between bacterioviruses and eukaryoviruses (since these FSFs were absent in one of the two viral groups except for the 20 common BE FSFs, Figure 3A). While, this may represent the generic trend, we noticed that 6 BE FSFs unique to bacterioviruses had an f-value that was 25% higher in eukaryotic proteomes than the corresponding f-value in bacterial proteomes (highlighted in Table S5). For example, FSF d.344.1 (PriA/YqbF domain) was present in roughly 95% of eukaryotic proteomes and in only 2% bacterial proteomes (i.e., f-value differential of 93%). For another 22 BE FSFs, the differential in f-values was either negligible or below the 25% cutoff making it difficult to establish the likely direction of origin (i.e., from Eukarya to bacterioviruses or from Bacteria to bacterioviruses). In fact, only 18 out of 46 BE FSFs in bacterioviruses had an f-value > 25% in bacterial proteomes than the corresponding f-value in eukaryotic proteomes (Table S5). Therefore, closer inspection of BE FSFs in bacterioviruses indicated that both sources of origin could be considered likely, especially when accounting for the relative preference of bacterial species to become endosymbionts of eukaryotes and considering mechanical similarities between bacterial and eukaryotic cells (read below). The same was also true for 20 BE FSFs common to bacterioviruses and eukaryoviruses where the f-value differential was under 25% for 11 out of 20 FSFs. However, 37 out of 45 BE FSFs in eukaryoviruses had an f-value of 25% or greater in eukaryotic proteomes than the corresponding f-value in bacterial proteomes (Table S5) indicating that eukaryoviruses perhaps did not engage in genetic exchange directly from Bacteria (or bacterioviruses).
To test, we divided eukaryoviruses into five subgroups representing viruses of fungi, plants, metazoa, protozoa, and invertebrates-plants (viruses that can replicate in both plants and insect vectors), as defined by the NCBI Viral Genomes Resource (Figure 4). FSF distributions of the five subgroups of eukaryoviruses were mapped to the seven Venn groups already defined for eukaryoviruses (Figure 2). The majority of eukaryoviruses belonged to metazoa (n = 1,057) and plant hosts (963) revealing strong biases in the sequencing of human infection, livestock and agriculture related viruses. Interestingly, only 27 viruses were associated to protozoa. These viruses encoded a total of 291 FSFs (the second largest amongst the five eukaryoviral subgroups after 306 FSFs of metazoan viruses). This is expected since protozoa act as natural hosts of many "giant viruses" (e.g., Acanthamoeba polyphaga), which surpass parasitic cellular species both in particle and genome sizes and sometimes encode more than a thousand proteins (La Scola et al., 2003; Arslan et al., 2011; Philippe et al., 2013; Legendre et al., 2015). However, out of the total 65 BE FSFs detected in eukaryoviruses (Figure 2), 40 (62%) were detected in metazoan viruses and 32 (49%) in protozoan viruses (overlap of 14 common FSFs) (Figure 4). Animals are known hosts for symbiotic bacteria and also harbor large microbiota communities, especially in the gastrointestinal tract that is considered to be a "melting pot" for HGT (Shterzer and Mizrahi, 2015). Similarly, free-living amoeba (e.g., Acanthamoeba) are notorious reservoirs for both facultative and obligate intracellular bacteria and serve as "training grounds" to facilitate bacterial adaptation in eukaryotic cells (Barker and Brown, 1994; Molmeret et al., 2005). These two eukaryotic host subgroups therefore provide ample opportunities for eukaryoviruses to exchange genetic material either directly with bacterial proteomes or through prophages integrated in bacterial genomes.
Figure 4. Breakdown of the 489 FSFs detected in eukaryoviruses. Eukaryoviruses were divided into viruses of plants (included all plants, blue-green algae, and diatoms), metazoa (vertebrates and invertebrates), protozoa (animal-like protists), fungi, and a group that includes invertebrates and plants (IP). For each subgroup, bars indicate the percentage of FSFs present in one of the seven Venn groups listed on the right (see also Figure 2) and the percentage of virus-specific FSFs. Numbers on bars indicate actual count. n = total number of viral proteomes, m = total number of FSFs detected in viral proteomes.
The ABE and Virus-Specific Protein Folds (V) Provide Unique Insights into Viral Origins and Evolution
The ABE group was the largest Venn group for viruses of the three superkingdoms (i.e., 93 ABE FSFs out of 98 total FSFs in archaeoviruses, 319 out of 441 in bacterioviruses, and 315 out of 449 in eukaryoviruses, Figure 2). The ABE domains are, by definition, detected in the proteomes of all three superkingdoms and are more likely to evolve vertically and hold a deep history (Nasir and Caetano-Anollés, 2013, 2015). Indeed, ABE domains were widespread in cellular species (median f-value > 0.6 for all, Figure 5) and were enriched in "cell-like" functions such as metabolism, information, DNA repair, among others, and occasionally viral proteins (Tables S2–S4). Therefore, the ABE group stands in contrast to the "viral-like" nature of the other Venn groups, especially, B and E FSFs that had limited spread in cellular proteomes (Table 1). The presence of a large number of universal "cell-like" proteins in viral proteomes is therefore intriguing and worthy of exploration. It suggests two possible scenarios. First, the detection of ABE FSFs in viral proteomes effectively transforms ABE into an ABEV group, which now represents a large core of (near)-universal FSF domains shared by both cells and viruses. The mere existence of this FSF core supports an early "cell-like" phase in the evolution of modern viruses, an idea that has recently become popular (Nasir et al., 2012a,b) following the discovery of several "giant viruses" that overlap parasitic cells in physical and genome size (La Scola et al., 2003; Philippe et al., 2013; Legendre et al., 2014, 2015). Under this proposal, viruses are secondarily acellular as they either "escaped" or "reduced" from primordial cells before these cells diversified into superkingdoms (Nasir and Caetano-Anollés, 2015, see Schulz et al., 2017 for an opposite view). In an alternative second scenario, the ABEV group points to recent HGTs occurring between viruses and cells in either direction, more likely from cell-to-virus considering the cell-like nature of ABE FSFs. It is important to note that a single HGT event is sufficient to invoke transformation from the ABE to the ABEV group. For example, ABE FSFs can be transferred directly from Archaea to archaeoviruses, from Bacteria to bacterioviruses, and Eukarya to eukaryoviruses, in addition to indirect cross-superkingdom genetic transfers. All of these transfers suffice for ABE to ABEV transformation.
Figure 5. ABE FSFs are widespread in the proteomes of Archaea, Bacteria, and Eukarya. The f-value (number of proteomes in a superkingdom encoding an FSF / total number of proteomes in that superkingdom) distribution is plotted for the ABE Venn group of FSF domains for archaeoviruses, bacterioviruses, and eukaryoviruses. The three boxplots in each viral group describe FSF spread individually for Archaea (A), Bacteria (B), and Eukarya (E).
To evaluate these alternatives, we pooled the ABE FSFs of archaeoviruses (n = 93), bacterioviruses (319), and eukaryoviruses (315) into a non-redundant list of 442 FSFs (Table S6). Next, we dissected the 442 FSFs into seven new Venn groups: a (ABE FSFs detected only in the proteomes of archaeoviruses), b (ABE FSFs detected only in bacterioviruses), e (ABE FSFs detected only in eukaryoviruses), ab (ABE FSFs detected only in prokaryotic viruses), ae (ABE FSFs detected only in archaeoviruses and eukaryoviruses), be (ABE FSFs detected only in bacterioviruses and eukaryoviruses), and abe (ABE FSFs detected in archaeoviruses, bacterioviruses, and eukaryoviruses) (Figure 6). This classification enabled evaluation of virus-to-virus HGTs in contrast to either virus-to-cell or cell-to-virus candidate HGT events postulated above. The majority of the ABE FSFs were part of the be group (n = 130) once again suggesting relatively high activity of cross-superkingdom genetic exchange between bacterioviruses and eukaryoviruses (or their cellular proteomes) possibly driven by bacteria-eukarya lifestyle affiliations or, as an alternative, loss of these FSFs in archaeoviruses. The next larger groups included e (117) and b (102) (Figure 6). These could represent direct HGT events from bacterial proteomes to bacterioviruses and eukaryal proteomes to eukaryoviruses, respectively.
Figure 6. Breakdown of pooled non-redundant 442 viral ABE FSFs (see text) into seven possible Venn groups for archaeoviruses, bacterioviruses, and eukaryoviruses. Numbers on bars indicate actual count (see also Table S6).
A total of 66 ABE FSFs were detected in the proteomes of archaeoviruses, bacterioviruses, and eukaryoviruses (Venn group abe), again enriched in cell-like functions (highlighted in Table S6). The abe "universal" or "core" group of FSFs therefore included FSFs detected in the proteomes of all virus groups (archaeoviruses, bacterioviruses, and eukaryoviruses) and the three superkingdoms (Archaea, Bacteria, and Eukarya). While significant cross-superkingdom indirect genetic exchange cannot be ruled out, the possibility of the same HGT event occurring three times independently and in different ecological habitats should be considered unlikely. The origin of abe FSFs is therefore better and more parsimoniously reconciled with an origin of modern viral lineages in ancient cells that existed prior to the diversification of cellular life and experienced high levels of genome reduction (Nasir et al., 2012a; Claverie and Abergel, 2016). One interesting observation was the existence of only 2 FSFs belonging to the ae group. An origin of Eukarya from within Archaea has recently been postulated following the reconstruction of the genomes of the candidate archaeal phylum "Lokiarchaeota" and "Asgard" archaea (Zaremba-Niedzwiedzka et al., 2017), which harbor several eukaryote-specific proteins (Guy et al., 2014; Spang et al., 2015, see Nasir et al., 2016; Da Cunha et al., 2017 for opposite views). Under this scenario, one should expect stronger affiliation of eukaryoviruses with archaeoviruses, which however does not materialize in the FSF data.
Finally, 10 and 55 virus-specific FSFs (V) were detected in the proteomes of bacterioviruses and eukaryoviruses, respectively (none in archaeoviruses, Figure 2, Table 2). These protein domains represent crucial viral functions involved in viral pathogenicity and virion synthesis and could therefore become hot targets for designing novel therapeutics against contemporary viruses. Their origin however cannot be attributed to cell-to-virus HGT, as these FSFs are completely absent in cellular proteomes. They could originate either directly in viral lineages during replication inside host cells (refer to the "virocell" concept, Forterre, 2011) or represent ancient proteins relics of an early origin of viruses. Testing either of these two scenarios via data-driven approaches remains an open challenge though insights are starting to emerge (Nasir and Caetano-Anollés, 2015).
Table 2. Virus specific FSFs (VSFs).
A simple comparative genomic analysis calculating the spread of viral protein domain structure FSFs in reported host and non-host cellular proteomes revealed that proteomes of virus hosts harbored several viral hallmark proteins necessary for virion assembly and successful viral infection cycles (Table 1). These viral hallmark proteins however were absent from the majority of closely-related organisms within the same superkingdom indicating that their rare presence in some host cellular proteomes could be an outcome of virus-to-cell gene transfer. In turn, proteomes not presumed to serve as natural hosts for viruses also shared homologous FSFs with viral proteomes. These FSFs included both viral- and cell-like proteins. This was especially obvious for FSFs shared between bacterioviruses and eukaryotic proteomes indicating either direct or indirect cross-superkingdom genetic exchange. This sharing could have been driven by the endosymbiotic and pathogenic lifestyle of bacteria that sometimes associate with eukaryotic cells. Interestingly, despite sharing the same ecosystem with Bacteria (e.g., the human gastrointestinal tract, Lurie-Weinberger and Gophna, 2015), our results suggested that little or no FSF sharing (or genetic exchange) occurred between archaeoviruses and the proteomes of Bacteria and Eukarya (e.g., AB was 1 and AE 0 in archaeoviruses, Figure 2). Bacteria are established pathogens and (endo)-symbionts of eukaryotes but Archaea are not known to infect eukaryotic organisms (Aminov, 2013). The membranes of Archaea also differ in lipid composition with the membranes of Bacteria and Eukarya (ether-linked vs. ester-linked, Jain et al., 2014), along with other differences (Gill and Brinkman, 2011). These differences could therefore pose a barrier for archaeoviruses to cross/traverse bacterial and eukaryal membranes and participate in horizontal genetic exchange. In contrast and thanks to the relatively similar lipid organization of Bacteria and Eukarya, bacterioviruses may either directly traverse eukaryotic membranes or alternatively transduce benign bacterial species into human pathogens by transferring virulence factors (Brüssow et al., 2004), which in turn infect Eukarya. As stated by Gill and Brinkman (2011), "eukaryotic viruses infect eukaryotes, and bacteriophages transduce Bacteria, which allows them to infect Eukarya". Moreover, there are many more known examples of obligate and facultative intracellular bacteria (e.g., Chlamydia, Rickettsia, Mycoplasma) in eukaryotes. Therefore, viral infection of bacterial endosymbionts or prophage integration into their genomes will create more opportunities for genetic interactions with eukaryoviruses and eukaryotic proteomes explaining more "crosstalk" between bacterioviruses and Eukarya (and perhaps eukaryoviruses and Bacteria) than between archaeoviruses and Bacteria/Eukarya. However, it must be noted that both archaeoviruses and archaeal species are relatively underrepresented in sequence databases. Thus, a global picture of the true contribution of archaeoviruses and archaeal proteomes to protein structure space remains elusive despite increased metagenome sequencing efforts. Indeed, Archaea constitute an important part of the animal microbiota (Hoffmann et al., 2013; Lurie-Weinberger and Gophna, 2015), an ecosystem that is considered a "hot spot" for genetic exchange (Shterzer and Mizrahi, 2015).
A large cohort of universal protein domains shared between archaeoviruses, bacterioviruses, eukaryoviruses, Archaea, Bacteria, and Eukarya, was also detected that provides support to an ancient co-existence of viral and cellular ancestors before the rise of a diversified cellular world (abe FSFs, highlighted in Table S6), a scenario supported by a recent large-scale phylogenomic study (Nasir and Caetano-Anollés, 2015) and a number of philosophical arguments (Claverie and Abergel, 2016). Cross-superkingdom genetic transfers were also likely after the rise of diversified cellular lineages. In turn, the list of virus-specific protein domains (Table 2) provides a useful set of molecular targets for antiviral research.
The comparative genomic approach presented here is useful to postulate data-driven hypotheses regarding viral evolution, especially because large-scale sequence-based phylogenetic analysis on viral genes and genomes is sometimes prohibitive due to high nucleotide and amino acid sequence variability within and between viral genome groups. The comparative genomic approach however does suffer from some limitations. First, in the absence of phylogenetic reconstruction, structural similarities are considered homologies. Protein domain sharing could be a result of convergent evolution, HGT and vertical evolution. However, protein domains grouped into FSFs are believed to have evolved from a common evolutionary ancestor and thus cannot (by SCOP definitions) be subject to convergent evolution. Specifically, the interlocking of amino acid side-chains in the buried cores of protein domain structures represents a distinctive "fingerprint," which is recognizable among member domains of any particular superfamily. Amino acid substitutions that occur over evolutionary timespans do not distort the 3D fingerprint characteristic of each superfamily without risking loss of the protein fold, and ultimately its biochemical function (e.g., bacterial MreB and FtsZ proteins that are prokaryotic homologs of eukaryotic actin and tubulin, respectively). That is the reason why despite low sequence identities, member protein domains of SCOP FSFs share recognizable structural and biochemical similarities, which are taken as evidence for common origin. Empirically, the odds of originating the same fingerprint (a product of multiple interactions occurring between many amino acid side chains) independently are considered to be extremely low (e.g., between 3 and 5% in Gough, 2005). In other words, each known fold or FSF is a unique discovery in evolution. Given the small number of expected folds that exist in nature (~1,500), convergence becomes an unlikely scenario.
Second, HGT can transfer protein domains and thus increase their representation in modern proteomes. We used the f-value as a proxy to evaluate the relative evolutionary spread of each FSF in cellular proteomes. When linked with the biochemical function of the protein fold (i.e., viral-like or cellular-like), the analysis indicated a likely direction of gene transfer (i.e., virus-to-cell or cell-to-virus). For example, FSFs involved in a viral hallmark function such as virion synthesis and/or capsid assembly that had negligible presence in either host or non-host superkingdoms (e.g., f < 1%) were treated as candidate virus-to-cell gene transfers. In turn, FSFs involved in cellular functions such as metabolism that were widespread among cellular proteomes (e.g., f > 60%) were treated as cell-to-virus candidate HGTs, except when these FSFs were also detected in the three virus groups (i.e., the abe group of 66 "universal" FSFs). This approach of inferring a qualitative likelihood of HGT is thus similar to the method of detecting anomalous phylogenetic distributions of genes where rare presence of a gene in closely related members is more likely a result of HGT rather than vertical evolution, especially because the latter would require invoking multiple events of gene loss that are less parsimonious than considering fewer HGT events (Philippe and Douady, 2003). The f-value approach is especially useful for viral genes that exhibit fast mutation rates and prohibit utilizing genome-scale alignment-dependent phylogenetic analysis (Abroi and Gough, 2011; Nasir and Caetano-Anollés, 2015).
Third, it can be argued that the f-value may not reflect phylogenetic diversity. For example, an f-value of 0.05 indicates rare presence but the FSF could be specific to a particular phylum or group of organisms (e.g., Firmicutes). However, and to emphasize, the f-value was coupled with known biochemical functions of the protein fold, i.e., viral-like (e.g., virion assembly) or cell-like (e.g., metabolism) functions, which was then used as composite variable to postulate the direction of candidate HGT event (see Nasir and Caetano-Anollés, 2013 for previous applications of the approach). When the molecular function of an FSF is well-known (i.e., cell-like or virus-like), it becomes easier to postulate a direction of gene transfer and to also exclude convergence as an alternative scenario. Moreover, FSFs that are specific to only one phylum (or a group of organisms) are likely not to be inherited vertically but after the divergence from the common ancestor of that group, a time period that follows virus-cell divergence.
Fourth, we raise the issue of coverage of viral proteomes, where coverage is defined by the number of viral genes (proteins) with significant homologs in either sequence or structure databases. We have previously shown that roughly >60% of viral proteins did not match to known FSFs (Figure 2B in Nasir and Caetano-Anollés, 2015). It is already well-known that the majority of viral genes lack sequence homologies, putatively termed ORFans (Ogata and Claverie, 2007; Yin and Fischer, 2008; Cortez et al., 2009). These viral genes either evolved fast and hence are no longer recognizable at either sequence or structure levels, or represent genes that originated directly in viruses (Forterre, 2011) (e.g., VSFs in Table 2). Determining the origin of viral ORFans remains an open and important question in virology research.
Finally, we only considered f-values of virus-encoded FSFs in cellular proteomes and not in viral proteomes. Viruses are notorious for encoding small-sized genomes that are likely a result of extreme genome reduction (Nasir et al., 2012a; Claverie and Abergel, 2013). In a recent analysis, we showed that only three viral FSFs had an f-value of over 0.3 (Nasir and Caetano-Anollés, 2015). This result is unsurprising considering that the 3,440 viruses of this study belong to seven different replication strategies, infect the many diverse groups of cellular organisms (see Nasir et al., 2014 for a mapping of virus replicons to their hosts), and in general harbor genomes and particle sizes that are minimalistic. The tendency of viruses to reduce genome size over long evolutionary timespans has effectively led to loss of information when extant virus genomes are comparatively analyzed with cellular genomes. Indeed, no single FSF could be detected in all seven viral replicon types (Nasir and Caetano-Anollés, 2015). Therefore, we caution the readers that the strategy reported in this study takes a modern-day snapshot of the proteomes of both viruses and cellular organisms and does not benefit from phylogenomic reconstruction. It is also dependent on the size of available genomic databases that are severely under-represented, especially, in archaeal and viral genome sequences. However, we do not expect that sequencing and discovery of novel viral and cellular lineages will drastically compromise our conclusions since we used a very strict threshold (e.g., f < 1%) in classifying an FSF to be acquired horizontally from viruses along with investigation of its biochemical function (e.g., virion synthesis). That is, future discovery of a virus-hallmark FSF in hundreds of newly sequenced genomes of a superkingdom that would significantly increase the f-values should be considered a highly unlikely event. However, discovery of novel viruses/cellular lineages can definitely add more virus-derived genes in cellular organisms thus adding to the lists of virus-acquired genes in cells or virus-specific genes (Table 2). Moreover, we restricted our analysis to the reference genomes of viruses and corresponding host organisms and to coding DNA. The next logical step is to perform a similar exercise on viruses recovered from metagenomic samples that are increasingly populating bioinformatics databases due to the continuous decline in sequencing cost and availability of fast and reliable high-throughput sequencing platforms. However, it can be sometimes challenging to establish host tropism in metagenome samples. Furthermore, there is no single universal gene (i.e., ribosomal RNA gene in cellular organisms) that can taxonomically classify short sequencing reads of viral metagenomes (Rohwer and Edwards, 2002). That is why we restricted our analysis to only well-curated reference genomes with virus host information available from experimental studies. Similarly, many viral genetic elements are permanently integrated into cellular genomes (Katzourakis and Gifford, 2010). This DNA also originated in viruses and thus should be considered the horizontal transfer of non-coding virus-to-cell transfer. While the virology community remains divided whether or not to include viruses in the realm of life (Claverie and Ogata, 2009; Moreira and Lopez-Garcia, 2009; Forterre, 2016), there have been recent important phylogenomic data-driven breakthroughs unfolding viral origins (Nasir and Caetano-Anollés, 2015). Past events such as FSFs lost via reductive evolution or species extinction leading to loss of ancestral FSFs cannot be accounted for in this analysis without phylogenomic reconstruction. Moreover, inferences drawn in this study are best parsimonious explanations consistent with reported data and lead to testable hypotheses. It is expected that a global dissection of viral and host proteomes will inspire debates and improve studies to better understand viral-host co-evolution.
Data Retrieval and Manipulation
Proteome data used in this study was taken from Nasir and Caetano-Anollés (2015). In brief, a total of 190,610 protein sequences corresponding to 3,966 completely-sequenced reference genomes of viruses that were available on the NCBI Viral Genomes Resource in June 2014 (Brister et al., 2015) were downloaded. Reference virus genomes are well-curated first genomes submitted for any virus species. Subsequent submissions of new genomes for that virus species are termed "genome neighbors." In our study, we only kept reference viral genomes, corresponding to any of the seven known viral replicon types (i.e., dsDNA, ssDNA, plus-ssRNA, minus-ssRNA, dsRNA, and retrotranscribing viruses) and excluding genomic neighbors, viruses that were listed as either "unclassified" or "unassigned" and deltaviruses.
Protein Structure Assignment
Viral proteins were scanned against a library of hidden Markov models (HMMs) (Gough et al., 2001; Gough and Chothia, 2002) maintained by the SUPERFAMILY database (ver. 1.75) (de Lima Morais et al., 2011) to detect SCOP FSFs using stringent E-value cutoff of 10−4. Viral genomes with no hits were discarded from the analysis. This reduced the viral dataset to include a total of 3,460 viruses including 1,649 dsDNA, 534 ssDNA, 166 dsRNA, 991 ssRNA, and 120 retrotranscribing viruses. Virus host information was available for 3,440/3,460 viruses (Bao et al., 2004) and was used to identify 62 archaeoviruses, 1,223 bacterioviruses, and 2,155 eukaryoviruses (Table S1). In parallel, pre-calculated FSF assignments for ~11 million proteins encoded by the completely-sequenced genomes of a total of 1,620 cellular organisms including 122 Archaea, 1,115 Bacteria, and 383 Eukarya were retrieved directly from the local installation of SUPERFAMILY MySQL database (July 2014). HMM assignments for viral proteomes can be downloaded from https://figshare.com/articles/Nasir_and_Caetano-Anolles_2015_zip/4833641.
Calculation of FSF Spread in Proteomes
The spread of each viral FSF in proteomes was calculated by an f-value, which represents the number of proteomes in a superkingdom (or virus group) encoding an FSF divided by the total number of proteomes in that superkingdom (or group). The resulting statistic is given on a scale from 0 to 1 indicating range from either complete absence (i.e., f-value = 0) to ubiquitous presence (f-value = 1). The index does not evaluate how heterogeneous is that distribution.
Determination of Virus-to-Cell and Cell-to-Virus HGT Events
Two factors were considered when postulating the direction of gene transfer (Figure 1): (i) the reported biochemical function of an FSF (e.g., virion synthesis or ATP synthesis), and (ii) spread of that FSF in the proteomes of cellular superkingdom(s). For example, if an FSF involved in capsid assembly (a virus hallmark function) was detected in only few cellular proteomes (e.g., <1%), then this FSF was determined to have transferred horizontally from virus-to-cell. In turn, if an FSF involved in cellular hallmark function (e.g., metabolism) and widespread in cellular proteomes (e.g., >60% presence) was detected in some viral proteomes then this was FSF was determined to have transferred horizontally from cell to viruses. The exception would be the presence of "cell-like" FSFs in the proteomes of all three virus groups, i.e., archaeoviruses, bacterioviruses, and eukaryoviruses, suggesting a cellular co-existence between viral and cellular ancestors prior to diversification of modern life (Nasir et al., 2012a,b). Thus, both the FSF spread and its biochemical function were considered when postulating the direction of gene transfer.
AN conceived the study. AN, KMK, and GCA designed the experiments. SSM and SAZ performed the preliminary experiments and wrote the first draft. AN, KMK, and GCA edited and improved the manuscript. All authors approved the study, final manuscript, and conclusions.
This work was supported by grants from the Higher Education Commission, Start-up Research Grant Program (Project no. 21-519/SRGP/R&D/HEC/2014), Pakistan to AN, from the National Science Foundation (OISE-1132791) and the National Institute of Food and Agriculture (ILLU-802-909 and ILLU-483-625) to GCA, and from the Collaborative Genome Program (20140428) funded by the Ministry of Oceans and Fisheries, Korea to KMK.
AN would like to thank members of the Computational Biology and Bioinformatics Group at COMSATS, Islamabad, for their support.
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmicb.2017.02110/full#supplementary-material
Table S1. List of viruses analyzed in this study. Also listed are virus replicon type, virus host, and known family/order.
Table S2. FSFs detected in archaeoviruses. FSFs are identified both by SCOP numeric IDs and alpha-numeric concise classification strings (ccs). The f-values are also listed for Archaea, Bacteria, and Eukarya. FSFs shared exclusively with non-host superkingdoms are highlighted.
Table S3. FSFs detected in bacterioviruses. FSFs are identified both by SCOP numeric IDs and alpha-numeric concise classification strings (ccs). The f-values are also listed for Archaea, Bacteria, and Eukarya. FSFs shared exclusively with non-host superkingdoms are highlighted.
Table S4. FSFs detected in eukaryoviruses. FSFs are identified both by SCOP numeric IDs and alpha-numeric concise classification strings (ccs). The f-values are also listed for Archaea, Bacteria, and Eukarya. FSFs shared exclusively with non-host superkingdoms are highlighted.
Table S5. The composition of BE Venn group in bacterioviruses and eukaryoviruses. FSFs are identified both by SCOP numeric IDs and alpha-numeric concise classification strings (ccs). The f-values are listed for Bacteria, and Eukarya. The difference in f-values was calculated by subtracting f-value of an FSF in Bacteria from the corresponding f-value for that FSF in Eukarya. FSFs with an f-value difference of over 25% are highlighted (yellow when f-value in Eukarya exceeds that of in Bacteria and blue for vice versa). Data sorted in an increasing manner for FSFs common to both bacterioviruses and eukaryoviruses, unique to bacterioviruses, and unique to eukaryoviruses.
Table S6. A non-redundant list of 442 ABE viral FSFs detected in all three superkingdoms. FSFs are identified both by SCOP numeric IDs and alpha-numeric concise classification strings (ccs). The f-values are also listed for Archaea, Bacteria, and Eukarya, and archaeoviruses, bacterioviruses, and eukaryoviruses. abe FSFs are highlighted.
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Keywords: virus host, protein structure, fold superfamily, comparative genomics, horizontal gene transfer, virus evolution
Citation: Malik SS, Azem-e-Zahra S, Kim KM, Caetano-Anollés G and Nasir A (2017) Do Viruses Exchange Genes across Superkingdoms of Life? Front. Microbiol. 8:2110. doi: 10.3389/fmicb.2017.02110
Received: 24 July 2017; Accepted: 16 October 2017;
Published: 31 October 2017.
Thorsten Allers, University of Nottingham, United Kingdom
David L. Bernick, University of California, Santa Cruz, United States
David Paez-Espino, Joint Genome Institute (DOE), United States
Copyright © 2017 Malik, Azem-e-Zahra, Kim, Caetano-Anollés and Nasir. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Arshan Nasir, arshan.nasir@gmail.com
†These authors have contributed equally to this work.


text:
The Personality of Pearl
March 19, 2014 by Kenny Smith 1 Comment
He said "I'm baaaaaaaack."
Jay Jacobs said "I just wish he had some personality."
It took Bruce Pearl less than two minutes to point out Gus Malzahn at Tuesday night's press conference in Auburn Arena introducing him as Auburn's new basketball coach . It took him 17 minutes to get around to his wife. In between he talked about his son, his assistants and the need to have your family with you in life.
"Chances are you're going to see me with my clothes on most of the time," Pearl said, but that wasn't the highlight of the night for a man seemingly full of highlights.
People keep asking — Is this real? Because right now, everything seems like a highlight from someone else's dream. When you listened to the gathered crowd sing him Happy Birthday, it was easy to wonder. Is this real? You could wonder, when he feigned a bit of "Aww shucks" and then directed the singalong before saying "How about if we make a deal? How about if we celebrate my birthday at the tournament next year?" It was easy to wonder. Is this real?
And when Jay Jacobs, caught up in the spirit of the thing, took a shot at the media, it was easy to wonder. When the crowd chanted for Gus, and you realized: these might be high water times in the athletic department, you could wonder, is this real?
Pearl vowed his team would work hard. He said they wouldn't be fun to play against. He reveled in the crowd's adoration. He glowed when he mentioned his contract. He made a joke about whether he could teach a class on ethics. The high-energy pizza provider, the salesman, so pleased to step back into the game he loved said, yep, this is real. And real, now, not next year. Pearl made a point of that: "The players will not hear me say 'When we get our own players.' Those are my players, right there, and I'm their coach."
The highlight of the night was perhaps when he said to the crowd and cameras that he is mindful, "as a coach and even as a father … I let a lot of people down … and so that's why I still walk around with pain."
As he talked about how he has found "this part of the country to be a part of the country that offers grace," you might have found a different side to the high-energy, enthusiastic, Personality of Pearl.
It is hard to imagine Sonny Smith or Tommy Joe Eagles or Cliff Ellis running into a thundering mass of students and fans on the airport tarmac. But Bruce Pearl is saying to anyone who will listen that he is grateful and that he has been humbled. To Auburn folks, that seems real.
And you remember: Auburn loves a comeback. And they've got their next feature performer. That's real.
Kenny graduated from Auburn at the turn of the century. He worked in newsrooms across the region and then earned a master's degree at UAB. He met and married a Yankee, who declared her Auburn allegiance at her first home game. She's now on the faculty at Auburn. He's finishing his PhD at Alabama and teaches at Samford University. And he's an assistant editor at The War Eagle Reader. See him online at www.kennysmith.org and @kennysmith.
Photos: Julie Bennett / al.com
Related: 'They could dominate Alabama': 'Pardon The Interruption' says Bruce Pearl great fit for Auburn basketball.
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redpajama_set_name: RedPajamaCommonCrawl


text:
Racist? Or Just Minority Interest?
We have a long running detective drama show in the UK called Midsomer Murders. It's been running for donkey's years and the format never changes. And neither does the plot. Basically each episode runs like this: a quaint, idiosyncratic, stereotypical English personage of a certain age who on the surface has their roiling emotions constrained by their stiff upper lip suddenly goes on the rampage and murders another quaint, idiosyncratic, stereotypical English personage of a certain age with something profoundly incongruous like a Black & Decker hedge trimmer or a Moulinex hand blender. Cue police investigation led by grumpy, cranky genius detective who solves the crime just in time to enjoy a cream tea at the local cricket club with his bridge playing wife and university graduate daughter. Cue titles.
Do feel free to take me to task (those of you who are fans of the show) if I have missed out any important plot points; I don't think that I have.
The show's creator, Brian True-May has, this week, got himself suspended by ITV chiefs for comments he made along the lines of "Midsomer Murders is the last bastion of Englishness" and he'd like to keep the cast all white as he feels to bring ethnicity issues into the show would change what the show is about. Basically he sees the show as being a fictional representation of an England that, if we're honest, has never really existed. It is a stereotypical view of what we (the English) and more likely what others (the Americans) would imagine is a traditional English village. Cricketing whites, tea and scones, old boys clubs, war veterans with walking sticks, toffs with chips on their shoulders and Mellors the gardener nobbing one of the posh ladies of the amateur dramatics society behind the back of her boorish husband.
It ain't real, folks, and it's never been real. But this is the show's very successful shtick. It has after all been running for over 14 years and been sold to 231 territories around the world (I wonder if any of those are Indian or African?).
The question is: is Mr True-May being racist in his adherence to a formula that has earned those very same ITV chiefs an awful lot of revenue over the last decade and a half. Is Midsomer Murders as a concept, racist?
'Cos the backstabbers are coming out of the ITV executive director's office with their knives of righteousness gleaming and freshly polished. They are "appalled" by his comments. An "investigation" has been launched. The story has even made the papers and the internet – no mean thing when it's hardly been what you'd call a slow news week.
I'm going to stick my head out here and say that, in my opinion, neither the show nor Mr True-May are racist. Not on your nelly. What he and the show are being, however, in non-representational. But that is very different from being racist. But – and here's the rub – the show isn't meant to be representational. It's a work of fiction. It taps into a stereotype of middle class Englishness and runs with it. Metaphorically the show is like drinking a cup of tea with your pinky sticking out. Chin-chin. Fancy a game of croquet?
I feel quite annoyed at the unspoken suggestion that the show should suddenly acquire itself an ethnic family just to tick that particular demographic box. I can't think of a more cheap, shallow and cynical reason to get a black actor onto the cast. And I'm at pains to point out here that I'm not a fan of the show. What I am a fan of though, is the freedom of writer's to be able to write what they like without having to jump through hoops just to appease the politically correct brigade who are so scared of offending anyone that they feel the imperative to impose the same restraints on every single show until all shows tick the same tick boxes and everyone is happy but no-one is watching the bloody show in the first place because it lacks character or individual personality.
Maybe I'm wrong. Christ, maybe I'm being racist. Am I? If the show was about an Asian village and about Asian life and values would someone be demanding a white family move in? Would that argument even get aired? Maybe that's over simplifying it – which is a bad idea as this topic is a bloody minefield as it is.
As far as I can see, the show is a cultural backwater. Literally. What sells the show is this fake, incestuous, closed-off Englishness that inevitably leaves little room for an ethnic dialogue. The show is not real and makes no attempt to engage with real life and the real culture of England which – thankfully – is wonderfully diverse and culturally rich. But that is this particular show's selling point. I think True-May is right. To meddle with that formula – for all it does little to appeal to me – would kill it off and ruin it for those fans who wish to suspend their disbelief and wallow for a couple of hours in a dream of England that didn't even exist in E. M Forster's time.
Ethnic issues are well represented on other shows and in other dramas. Nobody is being hard done by. What is happening is that the fear of racism and the fear of being perceived as being racist is resulting in a good many Union Jack bloomers getting themselves tied up into a right royal twist.
Chill out, people! It's a minority interest show! Doesn't that tick a tick box too?
For those of you that are interested here is the opinion of a Midsomer Murders viewer from India: Ramana's Musings...
P.S. Thank you for all reading my 700th post.
Posted by Steve at Wednesday, March 16, 2011
Labels: anniversary, culture, England, idiocy, ITV, MidsomerMurders, news, offensive, pathetic, politicalcorrectness, racism, television, UK, writing, xenophobia
AGuidingLife said...
A lot of the villages around me are exactly like that. They do exist. Honestly! I think the token minority person could be as offensive as none. I think they should just leave it alone. Agatha Christie would be turning in her grave. They may not be as 'politically correct' as they ought by they are a damn good read. I think the setting is relevant. You wouldnt put the token White person in a Pakistani Market nor the token aboriginal in the Cotswolds country fair. True representation makes for fair play UNLESS it is fictional writing then the writer should be able to write whatever they want. But it may need to be screened independently, not be the representational BBC.
Wednesday, March 16, 2011 12:05:00 pm
Happy 700th post! That's an amazing achievement, Steve!
I tend to agree with you. I always fall asleep halfway through Midsomer Murders (it tends to be rather long and as you say the plot is always much the same).
I certainly wouldn't be upset if they didn't have gay people in it (although I think they have from time to time - murderous ones no doubt!!) because it is just so far removed from real life anyway.
If you analyse it and think about it, the programme is annoying on all sorts of levels - the portrayal of marriage, women, class, British weather, the misrepresentation of rural areas as havens of murderous individuals - but I don't think we are meant to think about it, simply bask in its summery glow.
They should put in a Scotsman to widen it's appeal. A hairy-legged fellow in a kilt, who repeatedly pinches the big arse of a middle-aged spinster he fancies. I would call him McTavish. If there isn't a middle-aged spinster in the show it's a total travesty.
Kelloggsville: ooh! The BBC will be bristling with righteous indignation because Midsomer Murders is actually an ITV show! Shame on you! Other than that I totally agree.
RB: lovely to hear from you. The programme is indeed annoying! It's why I can't watch it. Unless I'm ill. In that situation I find I can mong out to it quite happily mainly because I am not in a position to think about it much.
Gorilla Bananas: there are spinsters aplenty (is this representational of a typical English village?) and I for one would be very happy to see a big gingery Scotsman tossing his caber into the village boating pond while encouraging the locals to indulge in a good old hootenanny...
Wednesday, March 16, 2011 1:00:00 pm
Nota Bene said...
700? get on with some work!
I didn't know Midsommer Murders was still going until the furore...strikes me that it's as anachronistic as you can get...and it should stay that way..that's the appeal to the people who watch it. You can't make all things appeal to all people...or at least you shouldn't.
Mind you that Kumars at 42 was pretty damn racist wasn't it? :-)
Nota Bene: not to mention Goodness Gracious Me...? ;-) I think you've hit the nail on the head far more succinctly than I managed. The show is anachronistic - and that is it's one (and possibly only) selling point. You'd have to be a dunderhead to change it.
Sorry I can't comment just now. I'm waiting for the gardener to turn up: we only have an hour or two before rehearsals in the village hall later.
Trish: not called Mellors is he...?
the fly in the web said...
700 posts...and unlike Midsomer Murders no one has dropped off half way through a post.
Lang may your lum reek, Steve.
What lobby or pressure group are the ITV bosses so afraid of?
Might as well put a band of asians grooming young English parlourmaids into an episode of Miss Marple.
The fly in the web: shhh - Andrew Davies is a local writer. Don't want to be giving him ideas for his next period drama...!
700 posts? Well done!
I am a huge fan of Midsomer Murders. My mum and I have spent many a Sunday afternoon watching it.
The appeal IS the farfetchedness of it all...the fat old doctor sleeping with all the beautiful women, the fact that there have been over 200 murders in such a small area...about a quarter of them, Mrs Barnaby just happens to witness!!
If you try and add anything into that mix for the sake of political correctness then it becomes serious, and that's not what the show is all about. It isn't The Bill for heavens sake!
They should all get off of their PC soap boxes as far as I'm concerned.
clareybabble: it is not The Bill. There is a true endorsement if there ever was one! ;-)
it's crap isn't it! not the show, I don't know, it competes here with Cold Case so I never watch it,
the idea. Another case of common sense being chucked out the window.
MissBehaving: a case of commonsense being birched, branded and stoned and then paraded through the streets in chains before being hung, drawn and quartered and then its suppurating remains burned at the stake. Yes, absolutely.
Marginalia said...
Dear Steve, I live in a tiny village in a county that was disbanded in the 1970's. We've not forgiven Ted Heath.
We don't have a single TV in the village; not because we wouldn't like it but because we live in such a deep dale that we can get no signal.
"The Archers" is brought round weekly by the mobile library in cassette form and we pass it and the cassette recorder around the village.
The last colour person to appear in our village was an Indian Raj who'd lost his way and after a futile attempt at opening an Indian restaurant converted to CofE and is now the verger of our lovely 13th century church which retains its original font.
Although it's not called into use much these days as most of the women in the village are past child bearing age.
We do have a policeman but we share him with the next village 4 miles away.
What crime we do have is fairly petty: sheep stealing, incest and the occasional gang rape.
Otherwise we're an extremely normal, quite English village.
For your description of the goings on in your village it all seems rather over dramatic. Is it by any chance near a film studio: I just wondered if most of the residents were out of work actors. They do seem slightly "kooky".
Ah, well must dash. We're burning the local policeman this evening. That nice reporter Alan Wicker's here to cover it.
PS. I dictated this message and a very nice young man said he'd e-mail it to you.
Susan George
Dear Susan, when you say "burning the policeman" and Alan Wicker covering do you mean that the poor plod will be installed inside a giant Wicker man loaded with faggots and kindling? If so, I'd like to come along and roast some marshmallows on the resultant blaze if I may... it's been a long while since I attended a pig roast.
Seeing as the show has been running for 14 years, it seems a bit late to be getting up in arms.
I think it's great. I watch it when I get home from work, the first 20 minutes from the trampoline, the last 40 with a cup of tea. It's perfect relaxing watching.
I think Brian True-May has been shamefully treated and I hope he is reinstated with an apology (and a G&T).
Dan said...
The fuss wasn't about there being no black or asian characters in the show (although for the length of time it's been going, with a new set of characters every single episode, the omission is very glaring)
The fuss is about the producer saying that to include a character from an ethnic minority would make the show less English. And he didn't say this in private - he said it to a national magazine.
He's an arse, and deserves his suspension.
Sarah: it does seem a bit late to complain now - and certainly given the show's obvious global popularity! It's not just middle England that likes it!
Dan: it depends what is meant by "English". As I've said the show has never meant to be representational - not of demographic breakdowns of population and certainly not of reality. The show has always struck me as being a bit of an in-joke - it has it's tongue firmly in its cheek. Seems to me the "English" Mr True-May was speaking of was a fake, stereotypical Englishness. The show has never set out to be a gritty mirror of reality. Lord knows there are plenty of other cop shows that do that. The Englishness that the show pitches for is that rosy cheeked, green gardened Englishness that you see on biscuit tins and decorated plates. It's never pretended to be anything else other than that. It is fake. To make it "real" would depart from the show's shtick. However, as I've already said, I don't really like the show. It's fakeness and contrivance annoys me. I don't think it's racist just a bit flat and 1 dimensional.
I tend to agree with your distinction between the show non-representational as opposed to overtly racist.
But I also agree with Dan that he's a prat to say that including ethnic minorities would make it less English. But then we get into the minefield of what we mean by 'English". I suspect what he meant was 'stereotypically middle class, country village, tea and scones, English' - which is what the show is about - but he's still daft to say it.
And on a different note. How come the Boycott American Women idiot has turned up on my blog too! Can't you send him to Midsummer Whotsit instead.
Have to be honest, I've never seen it, although I suspect Mr True-May is right...but in a sort of 'if it aint broke why fix it' kind of way..and as you say Steve it isn't real.
oops forgot! Happy 700th post!
Mark: I could certainly try and send Mr Boycott to Midsomer but I dare say his acceptance there will depend on his ethnicity...
Libby: it ain't real at all and I don't think anyone can watch the show and imagine for a minute that it is real. It's like a pantomime. Thank you for congratulations!
joebloggs said...
I dont think its trying to be anything other than what it is, a fctional story set in a fictional village.
If it was to be "inclusive" then as the story is so hackneyed and predictable then any black actor would either have to be the murderous drug dealing crim from the "smoke" or the victim, dead in the first 30 seconds. I for one would prefer being left out of it all together.
As for True-mays comments, he's entitled to his opinion.
I am not sure if it is still the case but up until last year the National Farmers Union only had one black member. He was on Country file once and dressed in his bottle green cords, check flannel shirt and wax coat was the epitome of English farmer, even his dog was called blacky...(probably?)
No Midsummer would not be the same with Normski or Dizzy Rascal as the new landed gentry, even they would draw the line at such fantasy!
Just remembered, was in a little "English" village in Suffolk last summer for a weeks hols and in all the time I was there I only saw one other black person. We had a little game of acknowlaging each other with a nod each time we saw each other.....(at least I think it was the same guy, they all look the same to me)
Joe: the unpalatable truth (unpalatable to the right-on press and ITV execs) is that there are actual real-life villages in the UK who do not have a single "ethnic" member. I'm not saying they are to be recommended (or even denegrated) but they do exist - they don't, however, to my knowledge harbour over 200 criminals and murderous crimes. Back in the days when it was difficult for a black actor to find work, shows that only employed white actors could be accused quite reasonably of racism. These days it is not the case - thank God. Not only do we have some wonderful black and Asian actors in this country but - even better - they win parts simply by the quality of their acting and not because the part "happens to be black". This is true progress. So to have an all white cast in the current, more liberated climate... is that still racist? I don't think it is. What's the difference between an all white cast for a production and all black cast? Both should be allowed if the script demands it without petty charges of racism being bandied about. To demand that a show has to have a black character or has to have an Asian character... well, to me, that is racist.
Congratulations on your milestone.
I`ve never watched `Midsomer Murders` - it`s too akin to the kind of tv I may have to watch in my nursing home, once I get there. Bad enough that they`ll make me eat the rice pudding.
ps not all middle-aged `spinsters` have big arses!just sayin`
Nana Go-Go: should we end up in the same nursing home I'll be the one singing "I like big butts and I cannot lie..."
I confess I was mightily disappointed in our English town, because the Midsomer Murders' village is exactly what I expected. I've been grumpy with the Englishman ever since he bought me across the globe to reside in a town lying in the shadow of an atomic bomb factory where the locals glow in the dark! I've lived in some of the most multicultural societies in the world and I know I'm not racist when I say that a writer should be free to write what he wants to write. I think putting the token Asian family into the mix would be bias, albeit positive bias, but bias that's a self-effacing apology and not at all genuine.
Vix: elegantly put. I bow to your superior lyricism.
Wylye Girl said...
Steve, The Husband worked with B T-M a few years ago. It's not an experience that he remembers fondly if you get my meaning. However, I live in what would probably be described as a quintessential English village with a village green, cricket club, pub and church. It also has no 'people of colour', or for that matter anyone who wouldn't tick the white/Christian box. The next village is the same and the one after that. My children's school of 1500 children has only a small handful of Asian/Africa heritage pupils, mainly associated with the army or local restaurants. It's not because we run them out of town, it's just because it is a very rural area and that's just how it is in many areas of rural England, whatever ITV may think. Unfortunately in the London-centric world of TV production, they think Hampstead or Wimbledon is 'the country' and don't seem to understand that there really are parts of the country where they inhabitants are all white.
Midsomer Murders has made B T-M a very wealthy man so I doubt that he would particularly care if he does get sacked as the exec producer and, with an average of 15 murders a year, you could forgive anyone for not wanting to live there ;) It's fiction, not fact and is sold in countries as diverse as South Africa, Saudi Arabia, Thailand and Malaysia. No-one has complained in 14 years so why not just leave it at that
The amount of murders that occur is this village means that there would be a high population turnover and you would think that eventually an ethic family would move in. The high crime rate would mean real estate prices are low LOL
Congrats on the 700th post, look forward to the next 700!
Thursday, March 17, 2011 2:03:00 am
Wylye Girl: "It's fiction, not fact and is sold in countries as diverse as South Africa, Saudi Arabia, Thailand and Malaysia..." that just says it for me. It's the idea of quaint Englishness that sells it - abroad as well as at home. If people want the reality of England they can tune into "Police, Cameras, Action"!
Vicky: Midsomer is not exactly somewhere that would be recommended on "Location, Location, Location" is it? ;-)
I'm all for positive discrimination on TV, but I do get tired of the formulaic shows that strive to achieve a perfect balance of male / female, white / black, straight / gay, able-bodied / disabled characters just to fill some pc quota rather than letting the story and characters dictate. I don't see anything wrong with having a show that has an all white cast, just as I never had a problem with the Cosby Show's all black cast. It's not necessary for every show on TV to tackle themes of race and equality - particularly quaint and harmless murder mystery shlock like this.
My Italian flag is out of my window to celebrate Italiy's 150th birthday today. My neighbours are not that keen. It's not racism but the narrowmindedness of a small village ...Ciao. A.
PS. Congratulations on your 700th post! And thanks for keeping on reading my blog. It looks like I'm blogging only for you! Ciao. A.
Rol: my point exactly. Midsomer Murders at the end of the day is just a piece of lightweight tosh. It has no higher agenda than to entertain the chattering classes for an hour or two. It is not meant to be thought provoking or culturally conscious. It's a bit of fluff.
Lunarossa: I wouldn't have a problem with an Italian flag being put out next door to me at all. And as for your blog... you mean you're not writing it just for me?
Congratulations on your 700th post Steve! Wow...
You speak of the truth only , it is the reality.
Janete: thank you - 700 posts... I feel like the old man of blogging...!
I had to return for your 700th post. I've never seen this programme but I guess I've not missed anything from the sound of it. As for an ethnic mix - when I was in Brittany I saw mainly white people and now I am in mid-Kent I see mainly white people. It's quite strange not to see a mix of people round here - they are noticeable by their absence
FF: welcome back - you've been missed. It sounds like Midsomer Murders may not be as nonrepresentational as I first thought... though I hope the murder rate is a lot lower where you are.
Bluddy Norah Steve! It's a bit busy in here tonight bloke. I've been so long in the queue outside your busy blog here, I've clean gone an missed most of the party. Well congrats then on becoming a DCC Blogga at last. What took you so long!
Excellent post though my friend. Totally agree with your sentiments and observations here, on top of which I really think you should forward this to Brian True-May and the head muppet at ITV, along with a copy of the following link:
http://www.bbcshop.com/comedy/fresh-prince-of-bel-air-the-season-1-dvd/invt/d068382/
If the BBC is still inherently regarded as the ethics and etiquette television media compass to pay regard and respect to on all things concerning 'race and representational balance' within the UK today – then why are they happy to promote and profit out of the sales of DVD's for the all black cast franchise series 'The Fresh Prince of Bel-Air' ?
The appearances of a 'non black' actor in the series were rare and very brief – and none of them bore character names. You'll probably find that ITV has shown this series too, or may well be still doing so. Time you gave them a bit of slap. You might even end up getting yourself "On the Telly!", dressed as a black jester.
No such thing as 'bad publicity' either. Jordan will end up a Baroness one day soon. You see. And she started off life as a black girl from Ethiopia by the way.
Phil: Jordan: As in Katie Price? Agree with you about the Fresh Prince - a good example of the other side of the coin and proves the point that if an all black cast is acceptable then the same should be said of an all white cast. Depends on the show and the context however. Thank God we've moved forwards from the days of the Blak & White Minstrel Show... but it seems we have still a way to go.
London City (mum) said...
Gotta love a storm in a teacup.
Oops. Is that a racist comment? Will the mugs be offended?
LCM x
Friday, March 18, 2011 4:58:00 pm
LCM: I think the mugs already are...
Sorry I'm late, feel like ym brain is operating on a different timetable to the rest of me these days.
Wow, 700 posts and worht every word and every visit! Well done.
I lost interest in Midsummer Murders once I realised that I was confusing it with Bergerac...and I didn't like that either. Ho hum.
Amanda: yes, Midsomer Murders is kind of like Bergerac only without the sea, the French and middle to lower class criminals. Other than that they are identical. Personally I blame John Nettles. They should have cast Lenny Henry instead.
It the body count in the village I'm worried about.
Congratulations on the 700 posts - here's to the next 700!
Have a good weekend Steve
Sorry I've not been on here much rather under the cosh at work and home at present - normal service will resume soonest
Löst Jimmy: totally understand - hope the cosh eases off soon, mate. In the meantime, hope you find some nuggets of R&R time to keep you going.
Saturday, March 19, 2011 8:40:00 am
Being Me said...
Happy 700th! You don't look a day over 697, though, you old charmer.
Being Me: flattery will get you everywhere - at the very least an invite to my 800th blog post birthday party...!
Hear Hear! Nail on the head as usual, Sir!
Livi: pity I can't hang a straight picture!
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