MicrobiologyBytes

The ongoing dance between a virus and its host shapes how the virus evolves. While human adenoviruses typically cause mild infections, recent reports have described newly characterized adenoviruses that cause severe, sometimes fatal human infections. A new paper describes a systems biology approach to show how evolution has affected the disease potential of a recently identified novel human adenovirus. A comprehensive understanding of virus evolution and pathogenicity is essential to our capacity to foretell the potential impact on human disease for new and emerging viruses.

Predicting the next eye pathogen: analysis of a novel adenovirus. (2013) MBio. 4(2): e00595-12. doi: 10.1128/mBio.00595-12
For DNA viruses, genetic recombination, addition, and deletion represent important evolutionary mechanisms. Since these genetic alterations can lead to new, possibly severe pathogens, we applied a systems biology approach to study the pathogenicity of a novel human adenovirus with a naturally occurring deletion of the canonical penton base Arg-Gly-Asp (RGD) loop, thought to be critical to cellular entry by adenoviruses. Bioinformatic analysis revealed a new highly recombinant species D human adenovirus (HAdV-D60). A synthesis of in silico and laboratory approaches revealed a potential ocular tropism for the new virus. In vivo, inflammation induced by the virus was dramatically greater than that by adenovirus type 37, a major eye pathogen, possibly due to a novel alternate ligand, Tyr-Gly-Asp (YGD), on the penton base protein. The combination of bioinformatics and laboratory simulation may have important applications in the prediction of tissue tropism for newly discovered and emerging viruses.

The peptidoglycan wall is a defining feature of bacterial cells and was probably already present in their last common ancestor. L-forms are bacterial variants that lack a cell wall and divide by a variety of processes involving membrane blebbing, tubulation, vesiculation and fission. Their unusual mode of proliferation provides a model for primitive cells and is reminiscent of recently developed in vitro vesicle reproduction processes.

Invention of the cell wall may have underpinned the explosion of bacterial life on the Earth. Later innovations in cell envelope structure, particularly the emergence of the outer membrane of Gram-negative bacteria, possibly in an early endospore former, seem to have spurned further major evolutionary radiations. Comparative studies of bacterial cell envelope structure may help to resolve the early key steps in evolutionary development of the bacterial domain of life.

L-form bacteria, cell walls and the origins of life. (2013) Open Biol. January 3: 120-143; doi:10.1098/rsob.120143 2046-2441

Malaria, toxoplasmosis, and related diseases are caused by infection with unicellular parasites called Apicomplexa. Their name refers to the elaborate invasion machinery that occupies the apical end of the parasite cell. This apparatus allows the parasite to force its way into the cells of its host, and to deliver factors that will manipulate host cell structure, gene expression, and metabolism. Once in the host cell the parasite will begin to grow. The parasite replicates its genome and organelles numerous times and then loads these various elements into numerous daughter cells that will further spread the infection.

This paper describes a fibre that coordinates the daughter cell budding process. The fibre links the centrosome, which controls the mitotic spindle, and the genome with the microtubule organizing center of the budding daughter. Parasite mutants lacking the proteins that build the fiber fail to form daughter cells at the earliest step. The fiber and its components are remarkably similar to fibers that coordinate flagella in algae. While Apicomplexa are not flagelated (with the exception of certain gamete stages) they evolved from flagellated algae. The authors propose that elements of the invasion apparatus evolved from the flagellum or flagellum associated structures.

Cell Division in Apicomplexan Parasites Is Organized by a Homolog of the Striated Rootlet Fiber of Algal Flagella. (2012) PLoS Biol 10(12): e1001444. doi:10.1371/journal.pbio.1001444
Apicomplexa are intracellular parasites that cause important human diseases including malaria and toxoplasmosis. During host cell infection new parasites are formed through a budding process that parcels out nuclei and organelles into multiple daughters. Budding is remarkably flexible in output and can produce two to thousands of progeny cells. How genomes and daughters are counted and coordinated is unknown. Apicomplexa evolved from single celled flagellated algae, but with the exception of the gametes, lack flagella. Here we demonstrate that a structure that in the algal ancestor served as the rootlet of the flagellar basal bodies is required for parasite cell division. Parasite striated fiber assemblins (SFA) polymerize into a dynamic fiber that emerges from the centrosomes immediately after their duplication. The fiber grows in a polarized fashion and daughter cells form at its distal tip. As the daughter cell is further elaborated it remains physically tethered at its apical end, the conoid and polar ring. Genetic experiments in Toxoplasma gondii demonstrate two essential components of the fiber, TgSFA2 and 3. In the absence of either of these proteins cytokinesis is blocked at its earliest point, the initiation of the daughter microtubule organizing center (MTOC). Mitosis remains unimpeded and mutant cells accumulate numerous nuclei but fail to form daughter cells. The SFA fiber provides a robust spatial and temporal organizer of parasite cell division, a process that appears hard-wired to the centrosome by multiple tethers. Our findings have broader evolutionary implications. We propose that Apicomplexa abandoned flagella for most stages yet retained the organizing principle of the flagellar MTOC. Instead of ensuring appropriate numbers of flagella, the system now positions the apical invasion complexes. This suggests that elements of the invasion apparatus may be derived from flagella or flagellum associated structures.

It’s a question half as old as time. “Where did viruses come from?” Over the last few years there has been quite a lot of activity in this area, in particulraly looking at whether the relatively new-discovered “giruses” (giant DNA viruses) represent a new domain of organisms or are part of the existing groupings (Archaea, Bacteria, and Eukarya). Recent work suggested that another domain was not necessary to accomodate these big viruses.

A new paper argues that the giruses may well have emerged via reductive evolution of cells, and that a new domain may be the right place to put them.

The battle continues – which side are you on?

Giant viruses coexisted with the cellular ancestors and represent a distinct supergroup along with superkingdoms Archaea, Bacteria and Eukarya. (2012) BMC Evolutionary Biology, 12:156 doi:10.1186/1471-2148-12-156
The discovery of giant viruses with genome and physical size comparable to cellular organisms, remnants of protein translation machinery and virus-specific parasites (virophages) have raised intriguing questions about their origin. Evidence advocates for their inclusion into global phylogenomic studies and their consideration as a distinct and ancient form of life.
Here we reconstruct phylogenies describing the evolution of proteomes and protein domain structures of cellular organisms and double-stranded DNA viruses with medium-to-very-large proteomes (giant viruses). Trees of proteomes define viruses as a ‘fourth supergroup’ along with superkingdoms Archaea, Bacteria, and Eukarya. Trees of domains indicate they have evolved via massive and primordial reductive evolutionary processes. The distribution of domain structures suggests giant viruses harbor a significant number of protein domains including those with no cellular representation. The genomic and structural diversity embedded in the viral proteomes is comparable to the cellular proteomes of organisms with parasitic lifestyles. Since viral domains are widespread among cellular species, we propose that viruses mediate gene transfer between cells and crucially enhance biodiversity.
Results call for a change in the way viruses are perceived. They likely represent a distinct form of life that either predated or coexisted with the last universal common ancestor (LUCA) and constitute a very crucial part of our planet’s biosphere.

Science Daily: Study of Giant Viruses Shakes Up Tree of Life

MicrobiologyBytes likes a good hypothesis – one that really makes you think, even if there’s not much actual data to support it. So here’s one for you: fungi ate the reptiles?

“Here are two indisputable facts: we are living in the age of mammals, and immunologically intact mammals are highly resistant to fungal diseases, such that most human systemic fungal are considered “opportunistic”. Could these two facts be connected? The mammalian lifestyle is characterized by endothermy, homeothermy, and care for the young, including nourishment via lactation, all of which are energetically costly activities. In contrast, reptiles, which are ectotherms, require about one-tenth of the daily mammalian energy needs, and reptilian development is faster and requires less parental involvement. Given this energy handicap, how did mammals replace reptiles as the dominant land animals? This essay further develops the hypothesis originally proposed seven years ago that fungi contributed to the emergence of mammals by creating a fungal filter at the end of the Cretaceous that selected for the mammalian lifestyle and against reptiles.”

Fungi and the Rise of Mammals. (2012) PLoS Pathog 8(8): e1002808. doi:10.1371/journal.ppat.1002808

Rapid evolution of RNA viruses is intimately linked to their success in overcoming the defenses of their hosts. Several studies have shown that rates of viral evolution can vary dramatically among distantly related viral families. Variability in the speed of evolution among closely related viruses has received less attention, but could be an important determinant of the geographic or host species origins of viral emergence if certain species or regions promote especially rapid evolution.

A new paper uses a dataset of rabies virus sequences collected from bat species throughout the Americas to test the role of inter-specific differences in reservoir host biology on the tempo of viral evolution. This shows the annual rate of molecular evolution to be a malleable trait of viruses that is accelerated in subtropical and tropical bats compared to temperate species. The association between geography and the speed of evolution appears to reflect differences in the seasonality of rabies virus transmission in different climatic zones.

These results illustrate that the viral mechanisms commonly invoked to explain heterogeneous rates of evolution among viral families may be insufficient to explain evolution in multi-host viruses and indicate a role for host biology in shaping the speed of viral evolution.

Rates of Viral Evolution Are Linked to Host Geography in Bat Rabies. (2012) PLoS Pathog 8(5):e1002720. doi:10.1371/journal.ppat.1002720
Rates of evolution span orders of magnitude among RNA viruses with important implications for viral transmission and emergence. Although the tempo of viral evolution is often ascribed to viral features such as mutation rates and transmission mode, these factors alone cannot explain variation among closely related viruses, where host biology might operate more strongly on viral evolution. Here, we analyzed sequence data from hundreds of rabies viruses collected from bats throughout the Americas to describe dramatic variation in the speed of rabies virus evolution when circulating in ecologically distinct reservoir species. Integration of ecological and genetic data through a comparative Bayesian analysis revealed that viral evolutionary rates were labile following historical jumps between bat species and nearly four times faster in tropical and subtropical bats compared to temperate species. The association between geography and viral evolution could not be explained by host metabolism, phylogeny or variable selection pressures, and instead appeared to be a consequence of reduced seasonality in bat activity and virus transmission associated with climate. Our results demonstrate a key role for host ecology in shaping the tempo of evolution in multi-host viruses and highlight the power of comparative phylogenetic methods to identify the host and environmental features that influence transmission dynamics.

Bacteria are generally distinguished from the cells of fungi, plants, and animals (eukaryotes) not only by their much smaller size but also by the absence of certain subcellular structures such as nuclei, internal organelles, and microtubules. Using state-of-the-art microscopy, this paper shows that microtubules do exist in some bacteria. These bacterial microtubules are built from proteins that are closely related to the microtubule proteins in eukaryotes. Bacterial microtubules are smaller in diameter than their counterparts in eukaryotic cells but have the same basic architecture. This paper proposes that bacterial microtubules represent primordial structures that preceded eukaryotic microtubules evolutionarily. Because bacterial microtubules can be produced and handled in the lab more easily than their eukaryotic counterparts, they may become useful tools for microtubule research and anti-cancer drug screening.

Microtubules in Bacteria: Ancient Tubulins Build a Five-Protofilament Homolog of the Eukaryotic Cytoskeleton. (2011) PLoS Biol 9(12): e1001213. doi:10.1371/journal.pbio.1001213
Microtubules play crucial roles in cytokinesis, transport, and motility, and are therefore superb targets for anti-cancer drugs. All tubulins evolved from a common ancestor they share with the distantly related bacterial cell division protein FtsZ, but while eukaryotic tubulins evolved into highly conserved microtubule-forming heterodimers, bacterial FtsZ presumably continued to function as single homopolymeric protofilaments as it does today. Microtubules have not previously been found in bacteria, and we lack insight into their evolution from the tubulin/FtsZ ancestor. Using electron cryomicroscopy, here we show that the tubulin homologs BtubA and BtubB form microtubules in bacteria and suggest these be referred to as “bacterial microtubules” (bMTs). bMTs share important features with their eukaryotic counterparts, such as straight protofilaments and similar protofilament interactions. bMTs are composed of only five protofilaments, however, instead of the 13 typical in eukaryotes. These and other results suggest that rather than being derived from modern eukaryotic tubulin, BtubA and BtubB arose from early tubulin intermediates that formed small microtubules. Since we show that bacterial microtubules can be produced in abundance in vitro without chaperones, they should be useful tools for tubulin research and drug screening.

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A new study has created a model of what scientists think the first multicellular cooperation might have looked like, showing that yeast cells – in an environment that requires them to work for their food – grow and reproduce better in multicellular clumps than singly.

Researchers found that cells of brewer’s yeast that clumped together were able more effectively to manipulate and absorb sugars in their environment than were similar cells that lived singly. The experiments showed that in environments where the yeast’s sugar food source is dilute and the number of cells is small, the ability to clump together allowed cells that otherwise would have remained hungry and static to grow and divide.

The work used the yeast Saccharomyces cerevisiae, which is commonly used in brewing and bread-making and has long been used by scientists as a model organism for understanding single-celled life. The researchers devised a series of experiments that presented two problems for the yeast cells to solve if they were to take in enough food to grow and divide: the first was how to change their food from an unusable form to a usable form; the second was how to actually take in this food. The researchers put the yeast in a solution of sucrose – table sugar – which is composed of two simpler sugars, glucose and fructose. Yeast lives on sugar, but the sucrose can’t get through the membrane that surrounds the cell. So the yeast makes an enzyme called invertase to chop the sucrose into glucose and fructose, each of which can enter the cell using gate-keeping molecules, called transporters, that form part of the membrane.

Working alone, a single yeast cell in a dilute solution of sucrose would never take in enough glucose and fructose to be able to grow and divide. But by cooperating, clumps of yeast in that same solution might have a chance. With several cells in proximity, all releasing invertase to create smaller sugars, these cooperating yeast cells would increase the density of those sugars near the clump, increasing the chances that each cell could take in enough to grow and divide. Sure enough, when the researchers tested these hypotheses on two strains of yeast, they found that the strain which clumped cells together was growing and dividing, while the yeast cells living alone were not.

Sucrose Utilization in Budding Yeast as a Model for the Origin of Undifferentiated Multicellularity. (2011) PLoS Biol 9(8): e1001122. doi:10.1371/journal.pbio.1001122
We use the budding yeast, Saccharomyces cerevisiae, to investigate one model for the initial emergence of multicellularity: the formation of multicellular aggregates as a result of incomplete cell separation. We combine simulations with experiments to show how the use of secreted public goods favors the formation of multicellular aggregates. Yeast cells can cooperate by secreting invertase, an enzyme that digests sucrose into monosaccharides, and many wild isolates are multicellular because cell walls remain attached to each other after the cells divide. We manipulate invertase secretion and cell attachment, and show that multicellular clumps have two advantages over single cells: they grow under conditions where single cells cannot and they compete better against cheaters, cells that do not make invertase. We propose that the prior use of public goods led to selection for the incomplete cell separation that first produced multicellularity.

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Recent studies have unearthed a treasure trove of prehistoric virus ‘fossils’, viral genomes or genome segments frozen millions of years ago as integrated copies in the genomes of diverse animal hosts. The fact that these integrated viral fossils can be easily recognized as belonging to modern virus families is stunning given the fact that modern exogenous viruses have replicated and evolved for many millions of years since these viral fossils were captured. Despite high rates of mutation, the evolution of virus sequence is clearly constrained. This constraint comes partially from intrinsic selective forces that limit virus evolution, such as selection for modulation of pathogenicity to the host and the structural constraints of the virus itself. Other major constraints on virus evolution come from the diverse immune strategies imposed by hosts. Cumulatively, these constraints act together to limit all aspects of virus evolution from the swarm of variants produced in a single host to the evolution of expanded host range. These newly identified fossils indicate that constraint on virus evolution might be far greater than has previously been appreciated.

Two-stepping through time: mammals and viruses. (2011) Trends Microbiol. 19(6): 286-294
Recent studies have identified ancient virus genomes preserved as fossils within diverse animal genomes. These fossils have led to the revelation that a broad range of mammalian virus families are older and more ubiquitous than previously appreciated. Long-term interactions between viruses and their hosts often develop into genetic arms races where both parties continually jockey for evolutionary dominance. It is difficult to imagine how mammalian hosts have kept pace in the evolutionary race against rapidly evolving viruses over large expanses of time, given their much slower evolutionary rates. However, recent data has begun to reveal the evolutionary strategy of slowly-evolving hosts. We review these data and suggest a modified arms race model where the evolutionary possibilities of viruses are relatively constrained. Such a model could allow more accurate forecasting of virus evolution.

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