Who benefits?

There's an interesting idea from evolutionary theory called the cui bono principle.

Cui bono? is Latin for "who benefits?"  It started out as a legal concept; if a crime has been committed, and you're looking for the suspect, find out who benefitted.  That, very likely, will get you on the right path toward solving the mystery.

Cui bono in the evolutionary model has to do with explaining odd phenomena that seem to have no obvious underlying reason -- or which even induce organisms into self-destructive behavior.  One common example is the strange situation where certain ant species crawl up to the tops of blades of grass and basically just wait there to be eaten by herbivores.  It turns out that the bizarrely suicidal ants are infected with a parasite called a lancet worm that needs to complete its life cycle in the gut of a herbivorous mammal, so it damages the brain of the ant in just such a way as to turn its sense of direction upside down.  The parasitized ant then crawls upward instead of downward to safety, gets eaten -- and the lancet worm, of course, is the one who benefits.

Another, even creepier example, is Toxoplasma gondii, which I wrote about here at Skeptophilia a few years ago.  I encourage you to go back and read the post, but the upshot is this parasite -- which by some estimates infects half of the human population on Earth -- causes different symptoms in its three main hosts, cats, rats, and people.  Each set of symptoms is tailored to change behavior in very specific ways, with one end in mind; allowing the parasite to jump to its next host.

I just found out about another very peculiar (and convoluted) example of cui bono just yesterday, this one involving rice plants.  Many plants, it turns out, have pheromonal signaling, releasing chemicals into the air that then trigger responses in neighboring individuals, either of their own or of different species.  Acacia trees that are browsed by herbivores, for example, emit a signal that triggers nearby trees to produce bitter tannins, discouraging further snacking on the leaves.  Well, it turns out that rice plants have an even niftier strategy; attacked by insect pests, the rice plants emit a chemical called methyl salicylate (better known as oil of wintergreen), which attracts parasitoids -- insects like chalcid wasps that attack and kill the offending pests, usually by laying an egg in or on them and allowing the larvae to eat the pests for lunch.

Okay, but this has yet another layer of complexity, because there's a different set of organisms that have another take on cui bono.  Rice are subject to a group of plant viruses called tenuiviruses, which cause rice stripe disease, weakening or killing plants and severely reducing crop yield.  Tenuiviruses are spread by insect pests like planthoppers, which (much like mosquitoes with malaria, dengue fever, yellow fever, and chikungunya) suck up the sap of infected plants and the virus along with it, move on to an uninfected host, and spread the disease.

Rice stripe tenuivirus [Image credit: A. M. Espinoza]

And new research has found that the tenuiviruses, once in an infected plant's tissues, suppress the plant's ability to produce methyl salicylate.  The result?  The plant can't send a signal to the parasitoids, the planthoppers multiply, and the disease spreads.

The authors write:

[R]ice viruses inhibit methyl salicylate (MeSA) emission, impairing parasitoid recruitment and promoting vector persistence.  Field experiments demonstrate that MeSA, a key herbivore-induced volatile, suppresses vector populations by attracting egg parasitoids.  Viruses counter this by targeting basic-helix-loop-helix transcription factor OsMYC2, a jasmonic acid signaling hub, thereby down-regulating OsBSMT1 and MeSA biosynthesis, responses conserved across diverse rice viruses and vector species.

So once again, we have a parasitic microorganism that is engineering a response in its host that makes it more likely to be passed on, in this case by preventing the host from calling for help.

This kind of strategy brings Tennyson's observation that "nature is red in tooth and claw" to new heights, doesn't it?  Makes you wonder how many other examples there are out there of behavior being manipulated by parasites.  Further evidence that evolution is the Law of Whatever Works -- even if Whatever Works is kind of unsettling.

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Who benefits?

One of the most curious features of evolutionary biology is the cui bono principle.

Cui bono? is Latin for "who benefits?" and is an idea that found its first expression in courts of law.  If a crime is committed, look for who benefitted from it.  In evolutionary biology, it's adjuring the researcher to look for an evolutionary explanation for seemingly odd, even self-harming behavior.  Somebody, the principle claims, must benefit from it.

A while back, I did a post on one of the strangest and most complex examples of cui bono; the pathogen Toxoplasma gondii, a protist that primarily infects humans, cats, rats, and mice.  In each, it triggers changes in behavior, but different ones.  It turns rats and mice fearless, and in fact, makes them attracted to the smell of cat urine.  Infected cats are more gregarious and needing of physical contact (either with other cats or with humans).  Humans are more likely to be neurotic and anxious, impelling them to seek comfort from others... including, of course, their pets.  Each of these behaviors increases the likelihood of the pathogen jumping to another host.

That this behavioral engineering is successful can be gauged by the fact that by some estimates three billion people are Toxoplasma-positive.  Yes, that's "billion" with a "b."  As in, one third of the human population.  I can pretty much guarantee that if you've ever owned a cat, you are Toxoplasma-positive.

What effects that has had on the collective behavior of humanity, I'll leave you to ponder.

I just ran into another cool example of cui bono a couple of days ago -- well, cool if you're not a tomato grower.  This is another one for which the answer to "who benefits?" turns out to be a pathogen, this time a virus called tomato yellow leaf curl virus, which has the obvious effect on infected plants.

Uninfected (top) and infected (bottom) tomato plants [Image credit: Zhe Yan et al., MDPI]

The researchers, led by Peng Liang of the Chinese Academy of Agricultural Sciences, noticed a strange pattern; there's a pest of tomato plants (and many other crops) called the silverwing whitefly (Bemisia tabaci) that shows a distinct preference for tomato plants depending on who is infected with what.  If the whitefly is uninfected with the virus, it's preferentially attracted to infected tomato plants; if the whitefly is already infected, it shows a preference for uninfected plants.

So cui bono?  The virus, of course.  Infected whiteflies pass the virus along to uninfected plants, and uninfected whiteflies pick the virus up from infected plants.  Clever.  Insidious, but damn clever.

Liang et al. found that the virus accomplishes this by meddling with a chemical signal from tomato plants called β-myrcene.  The virus actually up-regulates the β-myrcene gene -- essentially, turning the volume up to eleven on β-myrcene's production -- which attracts uninfected whiteflies.  Once the virus gets into the whiteflies, it dials down the sensitivity of the whiteflies' β-myrcene receptors, making them less attracted to it.  

No need to be lured in by the infected plants if you're already infected yourself.

So like with Toxoplasma, we have here a microscopic pathogen that is manipulating the behavior of more than one host species.  It's fascinating but creepy.  You have to wonder what other features of our behavior are being steered by pathogens we might not even be aware of.  Recent studies have found that between five and eight percent of our DNA is composed of endogenous retroviruses -- scraps of DNA left behind by viruses in the genomes of our forebears, and which are suspected to have a role in multiple sclerosis and some forms of schizophrenia.

Who knows what else they might be doing?

If you find this whole topic a little shudder-inducing, you're not alone.  Science is like that sometimes.  If there's one thing I've learned, it's that the universe is under no compulsion to make me feel comfortable.  If you agree, sorry I put you through reading this.  Go cuddle with your kitty.

I'm sure that'll make you feel better.

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Analysis of a partnership

You probably recall from biology class the word symbiosis -- when two organisms share living space.  This sort of relationship can result in a fused life form where even so, the two participants retain a discernible separateness.  (Remember the Trill from Star Trek?)  The melding can go deeper, though; lichens, commonly seen growing on rocks and tree trunks in damp areas, are an example of such a composite, in this case between one or more types of fungus and photosynthetic cyanobacteria.  Deeper still are mitochondria -- the organelles in all eukaryotic cells that conduct cellular respiration and provide the majority of the energy required by the organism -- which are the descendants of single-celled aerobic bacteria that billions of years ago formed a partnership with their host cells so mutually beneficial that now, neither can live without the other.

Symbiosis is usually broken down into three broad classes.  The distinction is how the participating organisms fare.  That one of them benefits in some way is a given; if both were harmed, the relationship would be strongly selected against and probably wouldn't persist very long.  It's what happens to the other that determines what kind of symbiosis it is:

• parasitism -- one organism benefits, the other is harmed (an example is disease-causing bacteria)
• commensalism  -- one organism benefits, the other breaks even (such as the bacteria passively riding on our skin)
• mutualism -- both organisms benefit (such as a good many of the bacteria in our gut, which have increasingly been found to be absolutely essential for health)

The trouble is, nothing in biology is clear-cut.  Our commensal skin bacteria occupy niches that, if they were eradicated, might be taken over by pathogenic species.  (Thus the adjuration by doctors not to overuse topical antibiotics and hand sanitizers.)  So are they actually mutualistic?  Then there are the species that help in some ways and harm in others -- or, perhaps, help one species and harm another.

This, in fact, is why the whole topic comes up today.  Scientists in New Zealand have been working to preserve endangered species on the islands.  There are quite a few, owing to the country's geological (and thus biological) isolation -- it's developed a singular group of endemic species that are uniquely vulnerable to loss of habitat from agriculture and from the introduction of exotic species like cats, pigs, and the ubiquitous sheep.  One such species is the rare Cooper's black orchid (Gastrodia cooperae), which is nearly invisible for most of the year -- the only above-ground part is a long, creeping stem -- and puts on a flower stalk once during the growing season.

[Image licensed under the Creative Commons Kathy Warburton/INaturalist (CC BY 4.0)]

Orchids are notorious for being difficult to grow from seed.  The seeds are minute, and most orchid species are extreme specialists, able to survive only in a very narrow range of conditions.  The result is that conservation efforts are fraught with difficulty.  Trying to germinate the seeds in the lab requires knowing exactly what that particular species needs, which can mean a lot of trial-and-error, and the potential loss of batches of seeds when the efforts fail.

The Cooper's black orchid is no exception.  It's so rare it was only identified in 2016, and is known to live in only three sites in New Zealand.  Fortunately for this species, there is a related orchid species, Gastrodia sesamoides, that is quite common and appears to need many of the same conditions that the Cooper's black does, so scientists have been trying to identify what those conditions are so they can be replicated in the lab.

And it turns out that one of the conditions is the presence of a symbiotic fungus -- Resinicium bicolor.  The fungus infiltrates the roots of the orchid, creating a greater surface area for nutrient and water uptake, much like the mycorrhizae familiar to organic gardeners that can increase crop yields without the addition of inorganic fertilizers.

Where it gets interesting is that Resinicium bicolor was already known to botanists -- as a plant pathogen.  It's a deadly parasite on Douglas firs, an introduced tree in New Zealand that is much used for lumber, causing "white-rot disease."

So is Resinicium a mutualist or a parasite?  The question is, "with respect to what?"  It's lethal to Douglas firs, but essential to the Cooper's black orchid (and, presumably, other native orchid species).

Biology, as I mentioned before, isn't simple.

That, of course, is why it's so endlessly fascinating.  The more we look into the complexity of the natural world, the more it brings home the truth of the quote from Albert Einstein: "Life is a great tapestry.  The individual is only an insignificant thread in an immense and miraculous pattern."

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Nice smile!

Back in December, I completely skeeved out some of my readers with a discussion of parasites, more specifically the protist Toxoplasma gondii.  Toxoplasma causes the disease toxoplasmosis, and a number of mammalian species are hosts, most notably cats, humans, and rats.  It's the cat/human connection that is why you've probably heard that pregnant women shouldn't clean cat litter boxes; contact with an infected cat's urine can transmit the parasite to a human, and Toxoplasma is associated with birth defects in human infants.

More interesting, though, are its behavioral effects.  In December's post, I described how toxoplasmosis alters the behavior of all three of its main hosts -- it makes cats more affectionate, humans more neurotic, and rats more fearless, all three of which serve the evolutionary function of increasing the likelihood that the pathogen will jump to another host.  (The cats seek out human company; the humans crave the comfort that pets can give; and the rats become unafraid of predators.  In fact, some studies have even shown that infected rats are actively attracted to the scent of cat urine.)

Which is creepy enough.  The idea that a brain parasite is, at least in some respects, in the driver's seat of our emotional state is a little unsettling.  Or maybe I'm only saying that because I've got it myself, having had cats off and on for pretty much my entire adult life.  But I'm not indulging in hypochondria, here; if you've ever owned a cat, especially one allowed outdoors, your chances of having a Toxoplasma infection is nearly 100%.  Kevin Lafferty, a microbiologist who is one of leading experts on Toxoplasma, estimates that there are three billion people in the world who have it.

Yes, that's "billion" with a "b."  As in just shy of 40% of the world's population,

But now another filigree of "holy shit, that is freaky" has been added to this already bizarre pathogen.  A team made up of Javier Borráz-Léon and Markus Rantala (of the University of Turku), Indrikis Krams (of the University of Latvia), and Ana Lilia Cerda-Molina (of the Instituto Nacional de Psiquiatría of Mexico City) found out that not only does Toxoplasma change our personalities, it changes our appearance.

The idea came from the fact that in other mammals, Toxoplasma can be spread through sexual contact, so there was no reason to believe the same couldn't be true of humans.  The researchers wondered if -- given that the parasite is pretty damn good at engineering its hosts to do things that pass it on -- there might be some way that being Toxoplasma-positive increased your likelihood of having sex.

And hoo boy, what they found.

They took a large test sample of infected and uninfected individuals, and rated them (or had others rate them, as the case may be) for a variety of features -- attractiveness (both self-perceived and as perceived by others), perception of healthiness, number of sexual partners, number of minor ailments, body mass index, mate value, handgrip strength, facial fluctuating asymmetry (i.e. asymmetry in features that change, such as how you smile), and facial width-to-height ratio, all of which could feasibly connect to sexual attractiveness.  

Some of the features (like handgrip strength and minor ailment susceptibility) showed no statistically significant difference.  But... well, let me quote you directly from the paper, so you don't think I'm making this up:

[We] found that infected men had lower facial fluctuating asymmetry whereas infected women had lower body mass, lower body mass index, a tendency for lower facial fluctuating asymmetry, higher self-perceived attractiveness, and a higher number of sexual partners than non-infected ones.  Then, we found that infected men and women were rated as more attractive and healthier than non-infected ones...  The present study offers novel evidence supporting the idea that some sexually transmitted parasites such as T. gondii may produce changes in the appearance and behavior of the human host, either as a by-product of the infection or as a result of the manipulation of the parasite to increase its spread to new hosts.

Which is probably why everyone finds me so dashingly handsome, and why my entire adult life I've had to fight off people trying to break down my bedroom door.

(Maybe having toxoplasmosis also makes you more sarcastic, I dunno.)

So.  Yeah.  That's not creepy at all.  Having a brain parasite causes you to look healthier and have a more attractive smile, and makes it more likely you'll get laid.  Who would have thought something that completely bizarre could be real?

Yeah, look at that smile. I bet you a hundred bucks David Tennant has toxoplasmosis. Maybe it even accounts for his amazing hair. [Image licensed under the Creative Commons Rach from Tadcaster, York, England, 2009 07 31 David Tennant smile 09, CC BY 2.0]

Interestingly, I wrote a short story called "The Germ Theory of Disease" (which you can read for free at the link provided) that riffs on this very idea -- a pathogen that makes you more social.  Unfortunately, it also turns you into a werewolf.  (C'mon, it's me we're talking about here, you had to know there'd be a paranormal twist.)

But hell's bells, I thought it was fiction.

And little did I know that I'm very likely to be carrying around a pathogen myself that does just that.  (Well, not the werewolf part.  I hope.)  Sometimes, as Oscar Wilde pointed out, life imitates art just as much as art imitates life.  Or, to quote Mark Twain, "The difference between reality and fiction is that fiction has to be believable."

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I contain multitudes

One of the things that even folks conversant in the evolutionary model sometimes don't know is the extent to which we are composite organisms.

On the gross level (and I mean that in both senses of the word), there is the sheer number of cells in us that are not human.  The adult human body has about 10 trillion human cells, and (depending on who you talk to) between 1 and 3 times more bacterial cells -- intestinal flora, bacteria hitching a ride on our skin, in our mouths, in our respiratory mucosa.  Most of these are commensals at the very worst -- neither harmful nor helpful -- but a significant number are in a mutualistic arrangement with us, which is one of several reasons why the overuse of antibiotics is a bad idea.

Then there are the little invaders we can't live without -- namely the mitochondria, those tiny organelles that every high school biology student knows are the "powerhouses of the cell."  What fewer people know is that they are actually separate organisms, descended from aerobic prokaryotes that colonized our cells 2.5 billion years ago (give or take a day or two).  They have their own DNA, and reproduce inside our cells by binary fission the same way they did when they were free-living proto-bacteria.

Mitochondria [image courtesy of Louisa Howard and the Wikimedia Commons]

But that's not all.  If you're a plant (I'm assuming you're not, but you never know), you have three separate ancestral lines -- your ordinary plant cells, the mitochondria, and the chloroplasts, which are also little single-celled invaders that now plants can't live without.  But even that's not the most extreme example -- the microorganism Mixotricha paradoxa is a composite being made up of five completely separate ancestral genomes that have fused together into one organism.

But back to humans, if you're not already so skeeved out that you've stopped reading.  Because it's even more complicated than what I've already told you -- geneticists Cedric Feschotte , Edward Chuong and Nels Elde of the University of Utah have just published a paper in which we find out that even our nuclear DNA isn't entirely human.  10% of our 30,000-odd genes and three-billion-odd base pairs...

... came from viruses.

We usually think of viruses as pesky little parasites that cause colds, flu, measles, mumps, and so on, but they're more than that.  Some of them -- the retroviruses (HIV being the best-known example) -- are capable of inserting genetic material into the host's DNA, thus altering what the host does.  Certainly, sometimes this is bad; both AIDS and feline leukemia are outcomes of this process.  But now Feschotte, Chuong, and Elde have shown that some of our viral hangers-on have had their genes repurposed to work in our benefit.

These stowaway bits of DNA are called "endogenous retroviruses" (ERVs), and some of them seem to be associated with cancer.  Others have been implicated in multiple sclerosis and schizophrenia.  But what the researchers found is that not all of them are deleterious; the gene that allows us to digest starch, and (even more importantly) the gene that triggers the fusion of the developing embryo to the placenta, seem to have viral origins.

"We think we’ve only scratched the surface here on the regulatory potential of ERVs," Feschotte said.

All of which is pretty amazing.  And it definitely gives one pause when you stop to think of how we define the word "organism."  Am I a single organism?  Well, not really.  Besides my regular human cells, I've got trillions of mitochondria, each with their separate bacterially-derived genome; and 10% of what I think of as "my DNA" came from viruses, at least some of which has then been modified into genes that I depend on to survive.  So humans -- and all living things -- are looking more and more like composite colonies of symbiotic life forms, representing a web of interrelationships that is so complex that it's mind-boggling.

So, to hell with the weird, exotic life forms from Star Trek.  I'm too busy being blown away by how bizarre and cool the life here on Earth turns out to be.