Botulinum toxin found in new, common bacteria

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Clostridium botulinum, Photo: Eye of Science

Evolutionarily, horizontal gene transfer between bacteria is generally not so groundbreaking. In this case however, it’s a little more newsworthy. A lot of bacteria carry plasmids, which are mobile little DNA structures that are not part of the bacterial chromosome and can be transferred to other bacteria. Often plasmids contain genes that may provide some selective advantage (otherwise why bother keeping them?), such as a toxin or an antibiotic resistance gene. Enterococcus happens to be frequent plasmid-carrier, which makes it an especially good candidate for frequent horizontal gene transfer. But first, Clostridium. 

Clostridum is an especially fun group of bacteria including some really famous germs:

  • C. tetani (Tetanus),
  • C. difficile (the bacteria in your gut that gives you stomach issues after you take antibiotics as it swarms in on all the spaces other bacteria used to be, before they were killed by antibiotics),
  • C. perfrinigens (perhaps the nastiest of all, gas gangrene),
  • the less famous C. sordelli (which is a rare–but plenty horrific, pregnancy and abortion-associated infection almost always resulting in death by toxic shock syndrome)
  • And of course, C. botulinum, the primary culprit of botulism.
What is Botulinum toxin?

C. botulium is known for releasing botulinum toxin (BoNT), a toxin which interferes with the release of the neurotransmitter—acetylcholine, from axon terminals at the neuromuscular junction resulting in flaccid paralysis (you can’t breathe).

The toxin (a protein) works by binding to receptors at the neuromuscular junction. It is then taken into the cell by receptor-mediated endocytosis. A conformational change occurs inside the early endosome (due to a pH change). A piece of the protein (the light chain) is translocated to the cytosol when another piece of the protein (the heavy chain) forms a sort of channel. This light chain can then cleave these important complex-forming “SNARE” proteins, which are vital to normal vesicular transport and neurotransmitter (which in this case is acetylcholine) release. So without these SNARE proteins, the little acetylcholine vesicles don’t get to where they need to be. In normal neurotransmitter release, SNARE proteins would work to tether the vesicles to the membrane so the cell and vesicle membranes could fuse to allow the release of neurotransmitters.

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Visualized by me on Pymol- PDB file: 3BTA, BoNT, Serotype A. You too, can play around with it in pymol/swissPDB/Chimera/some other visualizer!

Botulinum toxin is the deadliest toxin known requiring just two billionths of a gram to kill someone person. It’s so dangerous that when type H (one serotype of the toxin) was discovered and failed to be controlled by typical botulinum antibodies, the type H toxin became the only example of a genetic sequence that was hidden from public databases due to security concerns. I say “may be” because how would we really know?

Not just in C. botulinum anymore

While we used to take comfort in knowing we could probably avoid Clostridium botulium by just avoiding puffed up canned food, rotten meat, and organic honey, that may no longer be the case. For the first time, the botulinum toxin has been found in a completely different (and very distantly related) bacteria: Enterococcus.

This new variant of the toxin called BoNT/En, was found in South Carolina, in an E. faecium strain isolated from cows. And it wasn’t just the toxin that was found. Several associated proteins that prevent the toxin from being degraded were also found. That being said, the BoNT/En variant didn’t give the cow it was found in, botulism, and it was not actually very harmful initially in mice. Researchers had to manipulate the toxin to better target mice before it was able to actually kill them (I know. Trying to give mice botulism is upsetting, and the reason why I stick to cells and microbes for my research). They are testing the toxin on human neurons to see how toxic it is to humans.

Enterococci_Bacteria_Cluster
Enterococcus

What makes this particular jump so terrifying is that Enterococcus is a highly abundant group of bacteria all over our bodies. It is ubiquitous in animals and actually a significant human pathogen. E. faecium is a very hardy bacterium easily evolving antibiotic-resistance and actually pretty difficult to get rid of in hospital surfaces. The thought of a dangerous neurotoxin being easily transferred to a ubiquitous and antibiotic-resistant bacteria is somewhat frightening. That being said, plasmids containing incredibly dangerous neurotoxins would likely need to provide a selective advantage to the host to stick around (and it’s possible in E. faecium’s case, it could even provide a slight disadvantage). BoNT can be carried in a bacteriophage, in a plasmid, or on a chromosome, but carrying a sizable gene cluster you don’t need in evolution has usually resulted in a “you don’t use it, you lose it” outcome. As plasmids by themselves are slightly disadvantageous to carry, what keeps them around is any selective advantage the genes they contain provide.

Where did these toxins come from?

Researchers found that the homolog of BoNT in Clostridium, seemed to be a flagellin gene. These flagellins contain collegenase which breaks down peptide bonds in collagen, so they are also a proteolytic toxin family like the Clostridia neurotoxins. They believe that the neurotoxin and adjacent genesevolved from an ancestral collagenase-like gene cluster.  This gene cluster was likely duplicated and evolved separately to become the BoNT we know today.

My case against Botox: amazing, but maybe take it easy?

Botox can be useful for treating cerebral palsy, urinary incontinence, wrinkles, sweating, spasms, headaches, and tinnitus. While no one’s reportedly died from cosmetic Botox use (presumably because people are probably extra careful with such a terrifying substance), there’s a risk of the toxin spreading beyond the injection site and causing respiratory paralysis. While ordinarily I’m totally accepting of people’s desire to do strange or expensive things in the name of beauty, my (probably illogical) fear is that all it takes is one new guy thinking a smudged decimal point is a comma and you’re dead of flaccid paralysis.

Consider that a muscle with a cut nerve will quickly result in atrophy which will definitely make you look worse, not better. Not using your face muscles isn’t going to prevent you from wrinkling because the issue is not the muscles, but the soft tissue decline that comes with age. Neuromodulators like Botox are very expensive, usually require a high enough dose to actually be effective and wear off in a few months, meaning you would have to get several injections a year to stay smooth and shiny, and the repeated injections are when people tend to see more negative side effects and require a higher dose.

Paralyzing muscles over and over again is not great for you long-term so maybe try sunscreen, a nice skincare routine, and drink plenty of water instead? Mistakes happen, people misplace decimal points, I’d rather not be near it personally. Just a friendly PSA to remind you to definitely do your research if you want to mess around with botulinum toxin!

Sources:

  1. Sicai Zhang et al. Identification of a Botulinum Neurotoxin-like Toxin in a Commensal Strain of Enterococcus faecium. Cell Host and Microbe, 2018
  2. P.K. Nigam, Anjana Nigam. Botulinum Toxin. Indian Journal of Dermatology. 2010 Jan-Mar; 55(1): 8–14.
  3. Doxey AC, Lynch MD, Müller KM, Meiering EM, McConkey BJ. Insights into the evolutionary origins of clostridial neurotoxins from analysis of the Clostridium botulinum strain A neurotoxin gene cluster. 2008.
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Cryptococcus — (r)evolutionary genius

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If you’re in the market for a particularly fun fungus to tell your friends about, I’d suggest the pathogenic yeast, Cryptococcus.

Cryptococcus is primarily known for causing Cryptococcal meningitis—a leading cause of death in AIDS patients. This is Cryptococcus neoformans, which, while more common really only infects the immunocompromised. Its cousin, Cryptococcus gatti, frequently infects immunocompetent, healthy individuals and is an important emerging pathogen. Weirdly enough, C. gatti infections all seem to come from trees. The fungal pathogen has dispersed all over the world surprisingly, scientists believe, due to continental drift. In the past few years, there’s been large outbreaks of the less common Cryptococcus gatti in the Pacific Northwest/Canada and South Africa.

Sex has something to do with it

Cryptococcus needs a lot of sugar to reproduce, particularly inositol which is all over the human brain and spinal cord which is probably why Cryptococcus is known for causing meningitis. Cryptococcus (depending on the species) has between about 6 to 12 genes involved in inositol transport while most fungi have only about two. While inositol is needed for reproduction and results in higher virulence, which mating type the fungus is may also play a large role in pathogenicity.

In yeasts there are two mating types, MATa and MATα. MATα strains are able to produce an extensive hyphen phase in the haploid state called monokaryotic fruiting. All the clonal C. gattii VGII (or C. deuterogatti) that have been infecting people have notably been from the same mating type: Matα. MATα strains are capable of same-sex mating which could be the origin for the outbreak around Vancouver. In C. neoformans, MATα strains which have their own genes specific to that mating type, are associated with higher virulence (but there’s no evidence of this with C. gattii). 

From Springer 2010, isolations of C. gatti from human clinical, veterinary, environmental sources. Underestimation of actual prevalence.
Hypermutator

Researchers found that several isolated C. deuterogatti strains contained mutations in MSH2, one of the genes involved in mismatch repair (genes that fix DNA replication errors). The human homologous MSH2 gene has the same effect where humans with mutations in MSH2 can have Lynch Syndrome, where they’re prone to various cancers.

The mutations in MSH2 in fungi were tested and resulted in their genomes mutating at a faster pace but growing at the same rate as wildtype Cryptococcus strains. When exposed to stressful conditions however, such as antifungals like rapamycin and FK506, the mutant strains rapidly took over as they could quickly acquire resistance to drugs. In the process of acquiring drug resistance the strains actually decreased in virulence and were significantly weakened compared to the outbreak strains.

So the hypermutators are much more fit in stressful conditions and can rapidly outcompete the wildtype strains, however they make a less fit pathogen without significant selective pressures present. This brings up an interesting question in host-pathogen evolution—what kind of genome makes for an ideal pathogen? Fungi in general are lousy pathogens, especially in people. Certainly white-nose syndrome in bats and chytrid fungus in amphibians have devastated populations but there aren’t a whole lot of “in between” fungal pathogens. Having a lower mutation rate than bacteria or viruses contributes to their easiness to treat. While in bacteria a hypermutator strain rapidly evolving drug resistance usually sounds like a bad thing, in this case hypermutator strains taking over would at least lower the virulence and fitness of the fungus as a pathogen.

It’s even worse in men

As is the case with many pathogens, there is an increased incidence of the disease in men and when it does appear mortality rates are significantly higher in men. C. neoformans isolates from females had a slower growth rate and released more capsular glucoronoxylomannan (GXM), (a virulence factor and immunosuppressant). Testosterone was associated with higher levels of GXM release while 17-β estradiol was associated with lower levels and slower growth rate. Furthermore, macrophages from females were better at fighting off C. neoformans than macrophages from males which were more damaged from the infection. This may explain why infections are more common in men.

While Cryptococcus neoformans has been a common issue for a while, Cryptococcus gatti has only recently emerging as a prominent pathogen, which scientists believe could be the result of climate change. These Cryptococcus infections infect healthy people and are fatal if left untreated.

Sources:

  1. The second STE12 homologue of Cryptococcus neoformans is MATa-specific and plays an important role in virulence. Y. Chang-L. Penoyer-K. Kwon-Chung – Proceedings of the National Academy of Sciences – 2001
  2. The Role of Host Gender in the Pathogenesis of Cryptococcus neoformans Infections. Erin Mcclelland-Letizia Hobbs-Johanna Rivera-Arturo Casadevall-Wayne Potts-Jennifer Smith-Jeramia Ory – PLoS ONE – 2013
  3. Highly Recombinant VGII Cryptococcus gattii Population Develops Clonal Outbreak Clusters through both Sexual Macroevolution and Asexual Microevolution. R. Billmyre-D. Croll-W. Li-P. Mieczkowski-D. Carter-C. Cuomo-J. Kronstad-J. Heitman – mBio – 2014

 

Cretaceous pterosaur diversification and extinction

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Artist: Mark Witton

Few things are as disappointing as learning that no pterosaurs survived the K/Pg extinction. This has always been especially hard for me to emotionally accept due to their immense diversity. The typical explanation usually told is that they were wiped out with the non-avian dinosaurs after the chicxulub impact, and that they were barely alive by that time anyway because all the birds had filled up the flying niches. However recent evidence indicates that pterosaurs actually were doing very well up until 65 million years ago. Why they went extinct may have nothing to do with birds or a failure to diversify. Serial size reduction allowed for smaller pterosaurs to survive through other extinctions. Reaching sexual maturity before being fully grown allowed for smaller hatchlings maturing more quickly, allowing for more reduction in size by accelerating evolution somewhat. So if there were smaller pterosaurs at the end of the Cretaceous, AND pterosaurs have previously proven to be capable of relatively rapid phylogenetic size decreases, why did no pterosaurs survive?

The Cretaceous is more known for its giant, “small-plane sized” pterosaurs (Arambourgiania, Quetzalcoatlus, and one that’s been in the news more recently for “terrorizing” Transylvania: Hatzegopteryx). For background pterosaurs are split into two major suborders, with Rhamphorhynchoids being a paraphyletic group characterized by having teeth, long tails, and a cruropatagium that stretched between the feet (like how bats have it). Most were small and lacked bony head crests. They appeared in the Triassic and went extinct during the Cretaceous though there is no strong evidence to indicate they were outcompeted by pterodactyloids which is a common assumption.

Pterodactyloids, the other suborder, did not appear until the late Jurassic and were much more successful and diverse in the Cretaceous. While all pterosaurs are outstanding creatures, the pterosaurs this post is concerned with would all be pterodactlyoid members.

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Rhamphorhynchoid on left, Pterodactyloid on right

No fossils of pterosaurs have been found from after the K/Pg extinction (and I don’t believe there ever will be 😦 ). But while there are certainly no pterosaurs alive today, there is a lot of evidence indicating that pterosaurs were actually quite diverse even at the end of the Cretaceous, and that some were even very small. The discovery of small pterosaurs from the late Cretaceous does seem to indicate that the reason for their clade’s total extinction was not simply because they were just “too large.”

Small pterosaurs may have been more abundant in Cretaceous than previously thought

A small azhdarchoid (azhdarchoids being the most recent common ancestor of Quetzalcoatlus and Tapejara, and all its descendents) pterosaur was discovered from the Campanian Northumberland Formation of British Columbia. With an estimated 1.5m wingspan, the pterosaur specimen is described as being about the size of a large seagull. The specimen found might not actually be an azcharchoid, but it certainly was from a pterosaur. Researchers were able to analyze the bones to determine whether or not it was juvenile or adult and found that the specimen was either fully grown or very close to being fully grown. For more on that, read the paper here.

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Pterosaurs preserve terribly. They’re bones are hollow, their skeletons are fragile, they didn’t routinely die in nice, preserving environments. During the Cretaceous, pterosaurs shifted from marine to more non-marine habitats. This may account for the lack of data on small, difficult to preserve pterosaur fossils in the late Cretaceous. Terrestrial habitats do not preserve fragile fossils. Even much larger, denser bones do not often preserve well in terrestrial environments. The fossils that have been found from pterosaurs of this period are usually in very bad shape and are only fragments of the entire skeleton. Often times, fossils have to be looked at by many bird and pterosaur specialists before it can even be determined that the bone WAS from a pterosaur.  There is a lot of growing evidence suggesting that smaller pterosaurs in the late Cretaceous were not as rare as once believed.

Birds not the cause of pterosaur extinction

Pterosaurs were excellent fliers, almost definitely warm-blooded like birds (due to the energy expense of their lifestyle) and seemed able to adapt to a wide variety of niches. So it’s strange to imagine them going extinct due to their failure to diversify in the presence of birds. A study showed that pterosaurs actually diversified more after birds appeared. Pterosaurs had about a 160 million-year run on Earth and were relatively similar morphologically for the first 70 million years. They then began to experiment, trying out many modes of life. As birds became more successful, the pterosaurs actually responded by diversifying more. The emergence of birds (at least 50 million years after the first pterosaurs), encouraged the pterosaurs to try out new diets and feeding styles as seen by the rapid diversification of skull shapes in the fossil record. The general direction they went towards was much larger bodies. This was when the famous giant Quetzcoatlus types emerged.

sources:

  1. A small azhdarchoid pterosaur from the latest Cretaceous, the age of flying giants. Martin-Silverstone, Elizabeth, et al. Royal Society Open Science. 2016.
  2. Evolution of morphological disparity in pterosaurs. Katherine Prentice, Marcello Ruta, Michael Benton – Journal of Systematic Palaeontology – 2011

 

 

 

A microbe manipulating sex- and how it can fight Zika

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A fan favorite, and probably the most successful genus on the planet–at least on land—the bacteria, Wolbachia infects an estimate between 40 to 65% of all arthropod and nematode species. This microbe is constantly drifting across the line between mutualist and parasite to it’s host. Some hosts are unable to survive and reproduce without a Wolbachia infection whilst others are killed by it.

Wolbachia as a mutualist

Plenty of species have become reliant on this microbe. The caterpillar of the spotted tentiform leaf miner uses Wolbachia to create green islands on yellowing leaves which remain fresh for munching on.

It provides a benefit to certain nematode worms, such as Brugia malayi and Wuchereria bancrofti which cause elephantiasis, and which cannot survive without a Wolbachia infection. Image1.jpg

Some Wolbachia bacteria provide metabolic advantages to their hosts such as in bed bugs who use it to synthesize B-vitamins that are absent in their blood meals. Wolbachia can even mediate iron metabolism in Drosophila.

But most exciting given the recent explosion of flavivirus infections (Zika traveling farther and farther north every summer for example), Wolbachia provides flies with resistance to many RNA viruses.

Wolbachia as a sex-determinator

In leafhoppers, Zyginidia pullula, females have two X chromosomes while males have only one X chromosome, yet when infected with Wolbachia, the X0 genetic males appeared to be female.

Some females of the Japanese butterfly, Eurema mandarin have a sex chromosome system where the males are (ZZ) and the females are (ZWEurema_blanda_on_flower_by_kadavoor.JPG). This incongruence between chromosomal and phenotypic sex can be explained by feminization of genetic males induced by Wolbachia. Two strains of WolbachiawCI and wFem, have been found in E. mandarina and the females having male chromosomes (ZZ) are consistently infected with both wCI and wFem. However females with only wCI are true females (ZW). Despite having male chromosomes, ZZ females are physically female and fully fertile.

A similar thing happens in woodlice (pillbugs? Roly-polys?), where all the ZZ males infected with Wolbachia develop as female. The W chromosome is sometimes lost entirely in these populations and sex is entirely determined by presence or absence of Wolbachia.

Who needs males?

Wolbachia has evolved into an intracellular parasite, and while it can infect many different organs, it is most famous for infecting the testes and the ovaries. Wolbachia are too large for sperm, but fit nicely into mature eggs so the infection is inherited maternally through the eggs.

So now the evolutionary dilemma that keeps Wolbachia on the balance between parasite and mutualist is, if males are an evolutionary dead-end, how does this intracellular parasite that needs its host to survive and reproduce, and it’s host species to continue thriving, evolve to both spread throughout populations but not allow evolutionary cheater strains to ruin everything? Wolbachia has developed numerous ways of targeting males to help itself spread such as:

  • Male killing- infected male larvae die, so more infected females are born
  • Feminization- where infected males develop as females or infertile pseudofemales
  • Parthenogenesis- when females reproduce without males
  • Cytoplasmic incompatibility (CI)- when Wolbachia-infected males can’t successfully reproduce with uninfected females or females infected with another Wolbachia strain.CI-causing Wolbachia interferes with the chromosomes during mitosis so they no longer divide in sync.
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Warren et al, 2008, Nature Reviews, Microbiology.

Mosquitos carrying Wolbachia have a higher reproductive success when present in a population with mosquitoes not carrying Wolbachia. When a male mosquito carrying Wolbachia tries to mate with a female who is not carrying Wolbachia, the female’s eggs won’t hatch. However females with Wolbachia do not have this issue and produce perfectly healthy offspring which are all also carriers of Wolbachia. So you can imagine how the Wolbachia is able to sweep through a mosquito population. The female Wolbachia carriers have a much higher fitness than the non-carriers.

Scientists have taken advantage of this evolutionary strategy in fighting mosquito-transmitted viruses such as Dengue and Zika. The Aedes aegypti, a black-and-white striped species of mosquito infects people with Dengue virus which has no vaccine or real treatment and causes pains, fevers, rashes, and headaches. A plan (credited to evolution/ecology biologist, Scott O’Neill) to release Wolbachia infected mosquitos into the wild to lower dengue spread is becoming more and more popular. Wolbachia stops Aedes mosquitoes from carrying degue virus. Wolbachia carrying females have a selective advantage and should sweep through the population.

Wolbachia to rescue us from Dengue (and others?)- The original plan

An unusually virulent strain of Wolbachia the ‘popcorn’ strain, essentially halves the mosquito lifespand (it’s pretty gruesome, the bacteria essentially reproduce like crazy in the brains, eyes, and muscles filling up neurons). Dengue takes a long time to be able to reproduce and make it to the salivary glands so it can be transmitted, so only older mosquitos can transmit it.

Unfortunately Aedes (and Anopheles which transmist malaria) are not natural hosts of Wolbachia infections, so Scott O’Neill carefully developed a new symbiosis by injecting eggs. This took forever to work, until one lucky grad student was able to make it a success. Finally, an egg was stably infected and a line of Wolbachia-carrying Aedes was created. But after all that work, the strain was too virulent and the females did NOT have a selective advantage and actually had lower numbers of eggs with lower viabilities (honestly, they should have seen this coming really).

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But none of that even ended up mattering because some other scientists figured out that Wolbachia stops dengue virus from replicating. Simply the presence of a nonvirulent strain of Wolbachia in the population was enough to stop the spread of dengue. So the team switched to a less virulent strain, wMel, and successfully started a line of wMel carrying Aedes mosquitos.

wMelwAlbB update and some critiques of the data

As amazing as Wolbachia is, it will take at least a few years to get significant results and many years to eliminate any particular mosquito-transmitted pathogen with this method. Some papers say Wolbachia was able to make not only dengue, but also Plasmodium and other flaviviruses less able to replicate, but others said the opposite. It would be kind of important to figure out how the Wolbachia is inhibiting the virus because no one seems to agree if it’s general or specific. But now with significant selective pressures on all these diseases I’d suspect it’d be easy to switch host vectors because mosquitos bite hosts, geographically spreading infections very far (potentially) exposing the virus to a wide variety of new potential hosts vector species.

In a 2016 paper looking at the progress of the wMel strains, they collected Ae. Aegypti after one year and it continued to have low levels of dengue (which implies it was passed around through tons of mosquitos and not a whole lot of apparent evolution has taken place in terms of resistance) but what if the some of the dengue viruses switched species?

They could try passing the dengue through many mosquitos perhaps in a mixed host population. Or basically just try to provide the virus with as many opportunities as you can for it to evolve in the hopes that you may understand potential mechanisms the different diseases may have to get around this one Wolbachia infected species of vectors.

While the paper shows wMelwAlbB, the superinfection, that strain of Wolbachia actually doesn’t appear to inhibit DENV very much. But later in the paper, it’s very dramatically different so it’s difficult to say if the data is actually supporting that the superinfection sweep will work.

As far as how they ensure the right strain is dominating all the time given selective pressures towards different mosquito sex alteration methods, that remains unanswered. Combined male-killing CI strains readily become extinct following invasion so CI strains are more selected for but sex-ratio distortion decreases male infection and therefore reduces the occurrence of CI meaning that you might expect selective pressure for evolution from CI to CI/sex ratio distortion to sex ratio distortion only.

Wolbachia’s potential

Using Wolbachia’s ability to stop mosquitos from carrying Zika, Dengue, Chikungunya, Plasmodium—the parasite responsible for malaria, may mean the eventual elimination of these diseases in humans.

It may even be used to someday stop nematode worms from causing blindness, disability, elephantitis etc in many millions of people every year.

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Particularly inspiring about this story is how ecologists and evolutionary biologists ended up being the ones to figure out a way to eliminate viral infections. Yet more evidence that pre-med students or medical researcher hopefuls shouldn’t blow off biodiversity/ecology/evolution classes in college.

Sources

Kageyama, Daisuke, Satoko Narita, and Masaya Watanabe. “Insect Sex Determination Manipulated by Their Endosymbionts: Incidences, Mechanisms and Implications.” Insects 3.4 (2012): 161-99.

I contain multitudes: the microbes within us and a grander view of life. Ed Yong, 2016

Bacterium offers way to control dengue fever. Natasha Gilbert – Nature – 2011.

Establishment of a Wolbachia Superinfection in Aedes aegypti Mosquitoes as a Potential Approach for Future Resistance Management. D. Joubert-Thomas Walker-Lauren Carrington-Jyotika Bruyne-Duong Kien-Nhat Hoang-Nguyen Chau-Iñaki Iturbe-Ormaetxe-Cameron Simmons-Scott O’Neill – PLOS Pathogens – 2016

 

 

Homosexuality in animals

bottlenose_dolphin_1249780c.jpg Since it’s pride month, I thought the evolution of homosexuality warranted some attention. It turns out homosexuality is common throughout the animal kingdom, while homophobia is only seen in one species.

While sexuality is complex and seems to have a lot to do with epigenetics, as well as conditions in the uterus during fetal brain development, this variety is not limited to humans. Instead of thinking of humans as unique and separate from other animals, try to consider that brains, social structure, and cognitive ability exist on a spectrum with humans simply sometimes possessing a “higher degree” of whatever special unique thing we think we have. Such as love and sexuality. Homosexuality is especially common in primates and marine mammals (it’s correlated with intelligence in species). Same-sex relationships amongst animals strengthen social structures and can be particularly useful in systems with a lot of parental care, systems where the females outlive the males (humans?), and systems where not all males get an equal number of mates. Bottlenose dolphins for example are well-known for their bisexual behavior which strengthens social bonds.

When talking about homosexuality in nature, brief periods or episodes of homosexuality are actually pretty common. Male dominance mating (which is very common in giraffes), isn’t really “true homosexuality” because the males do not form any kind of bond, and the males will usually mate with females if they can. Cases of males or females rejecting the opposite sex and forming permanent pair bonds is more rare but absolutely happens.

Female-female couples

Young-albatross-female-couple-02.jpgA classic female-female coupling that actually makes a lot of evolutionary sense from a reproductive point of view, is the Laysan Albatross. The Laysan Albatross is monogamous and mates for life, and almost a third of the parent pairs are both female. This is useful as sometimes males will mate with more than the just their one female mate (basically he cheats on her in the hopes of making more offspring) and as the Albatross has evolved to require high parental care from both parents, female-female parents are actually a necessity in many cases where the father is absent.

Macaques are also rather known for their “lesbianism,” which in this case, has nothing to do with parenting and more to do with them just preferring sex with other female macaques. The males just can’t keep up.

Not all dominant mounting is males

While males mating with other males is very common, scientists have sometimes argued that a lot of that “mating” is simply the males exerting dominance over each other. Females do it to though, especially in the case of the female spotted hyenas who live in a matriarchy. The female hyena is even larger and more terrifying than the male hyena and leads the family.

Rams

gay-rams.jpgA study of gay sheep, was actually pretty historical as it really confirmed that there is a biological basis for sexual preference in animals. Sheep do seem to have a much higher rate of homosexuality than other animals where as many as 1 in 10 rams can be gay. Rams have undergone a lot of selective breeding which may provide some evidence that genes are involved in sexual preference. A region in the hypothalamus which is generally much bigger in rams than in ewes was found in gay rams to be the same size as the female’s. The hypothalamic region size variations effected levels of aromatase, an enzyme which converts androgens into estrogens. This supported the theory that hormones present during fetal development plays a role in determining sexual preference.

Bonobos

Bonobos are so closely related to us that it hardly seems worth it to mention them, but they are fascinating none the less. They exist in a peaceful (compared to chimps and humans) matriarchal society where sex occurs between basically every pairing you can imagine, excluding close family members (evolution doesn’t favor inbreeding). If you want to learn more about these super gay cousins of ours, I highly recommend primatologist, Frans de Waal’s books. He’s basically the top authority on bonobo sex. Really the best of the best.

Adoptive gay vulture dads
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In what may be one of the cutest stories I’ve read all year, two male griffon vultures from Amsterdam have recently been given the opportunity to raise a chick together. These two males are long-term mates who had been building nests together for months but were unable to produce an egg together (obviously). The zookeepers remarked that it was unfortunate as they were one of the most devoted culture couples observed.

Vultures are monogamous and have biparental care systems, so the males together could still make great parents. When a vulture egg was abandoned, and no heterosexual vultures would agree to incubate it, they gave the egg to the long-term male couple. The males ended up being very enthusiastic helicopter parents, proving that they could successfully hatch an egg even without a female helping. They carefully took turns incubating it, and when it hatched they proved to be protective, loving parents. The fathers have split their jobs equally, taking turns caring for their baby, looking for food, defending the nest, and feeding the baby.

Gay Penguins

Possibly the most famous gay couple in the animal kingdom is the penguin couple from the central park zoo, Roy and Silo. The two chinstrap penguins, where internationally celebrated for successfully hatching and caring for an egg they were given. Their caretakers noticed that they engaged in mating behaviors with one another and seemed to instinctually want an egg of their own, once seeming to try and hatch a rock that resembled an egg. Other gay penguin couples have been observed actually trying to steal eggs from other penguins, a behavior that’s not uncommon in heterosexual penguins either. Penguins typically engage in multiple long term relationships (kind of like humans do), and interestingly, many of them will switch around between male and female partners in their lifetime.

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sources

Oregon Health & Science University. “Biology Behind Homosexuality In Sheep, Study Confirms.” ScienceDaily. ScienceDaily, 9 March 2004.

Our Inner Ape, Frans de Waal

Polyploidy in tetrapods

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African Clawed Frog

Polyploidy is the condition where an organism possesses more than two sets of chromosomes. Most people probably only associate it with plants, as polyploidy in animals has been relatively understudied, and unisexuals—animals that are entirely female, are typically ignored because they use hybridization and parthenogenesis (though personally I think it may be male refusal to accept that they aren’t as permanent or resilient as they may have hoped—see the degenerate Y chromosome). The most famous female-only species are probably the New Mexico whiptails, Cnemidophorus neomexicanus, or “lesbian lizards,” a hybrid species of lizard that no longer involves males in their reproduction but still often perform courtship rituals to stimulate ovulation.

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Females perform courtship rituals to stimulate ovulation. Nature is amazing.

Both parthenogenesis (when eggs develop with no fertilization) and hybridogenesis (fertilization occurs but paternal DNA isn’t passed on) are pretty common in amphibians. A more intriguing example than the lizards, though one that’s gotten less press until now, is the unisexual Ambystoma hybrid salamanders. This salamander ranges from triploid to pentaploid with Ambystoma nothagenes using genes from males from three different salamander species– Ambystoma lateraleAmbystoma texanum, and Ambystoma tigrinum.

The Ambystoma females always require sperm from a related species to fertilize their eggs and initiate development and generally just discard the sperm genome. Sometimes the unisexual sexually reproduces instead and there is a genome addition or genome replacement event where the maternal genome is discarded or the female acquires the male’s genes and then keeps only some of the genes after mating.

What’s kind of intriguing about this case of “kleptogenesis”, or gene stealing, is that the females basically express genes from the different males at a relatively equal rate. How exactly they choose which genes to use and which to throw away is not known, nor is how these genes come together to make a good hybrid.

Why do it? 

How Ambystoma, a six-million-year-old lineage, and how other polyploids/unisexuals/hybrid species survive when in competition with “regular” diploids living in the same spatial niche, is also not understood. It’s generally considered that polyploidy is a short-term strategy evolved in environments that are less stable. Which is why Ambystoma being a polyploid for so long is especially surprising.

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Ambystoma, female polyploid

While polyploidy can be advantageous, it’s initially unstable before becoming a competitive strategy. The presence of duplicated genes can help fuel diversification and evolutionary success.

Heterosis, gene redundancy, and asexual reproduction can all be considered advantages of polyploidy. Heterosis is essentially the ability to make better use of heterozygosity. Gene redundancy allows you to better diversity and provides a protection from harmful mutations. And asexual reproduction enables you to reproduce without a sexual mate around.

Polyploidy in animals is a case of convergent evolution where many fish and amphibians have acquired it separately. All the polyploids have acquired their genomes differently and in different ways. The unisexuals and males in the salamander group have higher gene exchange than other polyploids which may explain the “balance” in the genome not seen in other polyploids. Instead of gene silencing or dominance evolving, it seems natural selection has favored a more balanced genome because that’s just what worked for these girls. If you lose some gene contribution it’s less dramatic this way than if you’d put almost everything into one male salamander only for him to do something inconvenient like die or not show up to mate.

Faster regenerators

There’s some serious selective pressures for salamanders to survive injuries. They have the ability to regenerate tissue, so if part of their tails snap off, they can grow back. A study published in the Journal of Zoology showed that these polyploid all-female salamanders regenerate lost tissue 36% faster than other salamander species.

Within 10 weeks, after having had 40% of their tails cut off, the all-female salamanders had full length tails. The diploid sexually-reproducing relatives needed another 5 weeks to finish growing their tails.

The explanation may have to do with more genes meaning more proteins meaning faster regeneration. And if you can’t regenerate you don’t do so well so this could have been an added pressure to explain how this lineage was able to stay polyploid for six million years.

Sources:

  1. J. Saccucci, R. D. Denton, M. L. Holding, H. L. Gibbs. Polyploid unisexual salamanders have higher tissue regeneration rates than diploid sexual relatives. Journal of Zoology, 2016;
  2. Comai, Luca. “The advantages and disadvantages of being polyploid.” Nature Reviews Genetics11 (2005)
  3. Kyle E. McElroy, Robert D. Denton, Joel Sharbrough, Laura Bankers, Maurine Neiman, H. Lisle Gibbs. Genome Expression Balance in a Triploid Trihybrid Vertebrate. Genome Biology and Evolution, 2017
  4. Evolutionary Significance of Whole-Genome Duplication. Mcgrath-M. Lynch – Polyploidy and Genome Evolution – 2012

The struggle against antibiotic resistance

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“Animals may be evolution’s icing, but bacteria are the cake.” –Andrew Knoll, Life on a Young Planet

Rapid evolution of multi-drug resistant bacteria due to overuse of antibiotics is one of the biggest threats facing humans today. Luckily scientists, motivated by terror of a superbug killing us all, have been working pretty hard recently on trying to solve this problem.

Teixobactin

A new class of antibiotics was discovered with the help of a new device, the iChip. Humans have been unable to figure out how to isolate and culture most (99%) of the Earth’s bacteria, but the iChip was successfully used to culture previously unculturable soil bacteria, notably Eleftheria terrae. This bacteria was found to produce Teixobactin, an antibiotic that micorbes have an exceptionally difficult time evolving resistance to (like, so difficult none have been able to do it yet). Because most antibiotics are usually discovered by accident via fungi or other microbes, being unable to culture most of what was in the soil has been a pretty big barrier in our search. Teixobactin is active against gram-positive bacteria and works by inhibiting cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). Peptidoglycan is what makes up the thick walls of Gram-positive bacteria. Gram-negative bacteria also have peptidoglycan but in much smaller amounts and are protected by a second outer membrane which Gram positive bacteria do not have.

Screen Shot 2017-06-06 at 8.38.59 PM.pngStaphylococcus aureus (MRSA/VRSA) and Mycobacterium tuberculosis (TB), two ofthe biggest names in the antibiotic resistance crisis, were both killed by and unable to develop resistance to, Teixobactin.

Teixobactin is probably more robust against mutations of pathogens, because of its antibiotic mechanism is so unusual. Most antibiotics involve binding to relatively mutatable proteins. Teixobactin however, binds to much less mutatable fatty molecules.

Vancomycin 3.0

Vancomycin has been in use since 1958 and was once considered a last-resort drug because it seemed bacteria were not very good at developing resistance to it but it’s a pretty serious drug. It has a higher toxicity level than most antibiotics you’d usually be prescribed so it is used only for the treatment of life-threatening Gram-positive infections. It kills bacteria by preventing cell wall synthesis by binding to peptides ending in two copies of D-alanine. Unfortunately bacteria were able to replace a D-alanine with a D-lactate (D-lac). Scientists decided to fix this by creating a new vancomycin that binds to peptides ending in D-ala and D-lalc. Other scientists came up with ways to manipulate vancomycin to kill cells by stopping cell wall synthesis in a new way or causing the outer wall membrane to leak.

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The new vancomycin, vancomycin 3.0, has three antimicrobial targets in one antibiotic. It was shown to be effective against vancomycin resistant Enterococcus (VRE) and vancomycin resistant Staphylococcus (VRS). A three-pronged approach presumably means that for a bacterium to be resistant, it would have to have three non-lethal mutations to get around this drug.

Phage-therapy

Bacteriophages, viruses that infect bacteria, are also being used as a method to treat bacterial infections. While this concept is not especially new, it’s been relatively neglected by the U.S.. Phage therapy would take a long time to get FDA approval and it still needs a lot more research. The coevolution of bacteria and bacteriophages, while certainly studied a lot in model organisms, is an important factor to consider when blindly expecting phage therapy to work. The nice thing about phages over antibiotics, is that antibiotics can sometimes have unpleasant side-effects, cause allergic reactions, or have high toxicity to the people/animals taking them. Phage are harmless and extremely specific to their targets, unlike broad-spectrum antibiotics. However phage are huge spreaders of antibiotic resistant genes as they are relatively important engagers in horizontal gene transfer (where genes, instead of being inherited, are picked up and incorporated into a genome via viral infection or collection of raw DNA).

Phage therapy saves man with multidrug-resistant infection
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credit:  Dr Graham Beards
 

In 2015, a four-phage cocktail was administered to target a man with a serious Acinetobacter baumannii infection which had been causing hallucinations and was killing his kidneys. This was the first instance of phages being used intravenously to treat someone almost dead due to an infection caused by a drug-resistant bacteria. Luckily he was married to a genius woman who happened to be an infectious-disease specialist and decided a phage-cocktail was his best bet. It was difficult trying to find the right bacteriophages but it worked in the end.

The Gram-negatives

One of the biggest struggles in finding new antibiotics is Gram-negative bacteria are often intrinsically resistant to antibiotics because their outer membrane is impermeable to large glycopeptide molecules, and so many antibiotics seem to target the cell wall.

Some Gram-negative bacteria that can cause pretty serious infections include Klebsiella (pneumonia, blood, wound), Acinetobacter (pneumonia, blood or wound infections), Pseudomonas aeruginosa (burns, wounds, respiratory), E. coli, Vibrio (Cholera), Yersinia pestis (“the plague”), and Neisseria gonorrhoeae (gonorrhea).

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Neisseria gonorrhoeae

Luckily, a lot of these don’t usually infect people (the first three basically never infect healthy people), however antibiotic resistant sexually transmitted diseases are actually on the rise in the United States and could become a very serious and difficult to control problem pretty rapidly. Gonorrhea’s not really a big deal if you catch it early and treat it, but it’s asymptomatic in many people (making them untreated, unknowing carriers) and left ignored, causes infertility and pelvic inflammatory disease.

So even though we might feel relief at these new discoveries, keep in mind that no antibiotic will work on all bacterial pathogens, and allergies to antibiotics are very common so we can’t just be left with a single last-resort. We kind of need a lot of options.

Sources:

  1. Okano, Akinori, Nicholas A. Isley, and Dale L. Boger. “Peripheral modifications of [Ψ[CH 2 NH]Tpg 4 ]vancomycin with added synergistic mechanisms of action provide durable and potent antibiotics.” Proceedings of the National Academy of Sciences (2017)
  2. “A new antibiotic kills pathogens without detectable resistance.” Ling et al (2015)