It’s not an arsenic-based life form

i-e88a953e59c2ce6c5e2ac4568c7f0c36-rb.png

Oh, great. I get to be the wet blanket.

There’s a lot of news going around right now about this NASA press release and paper in Science — before anyone had read the paper, there was some real crazy-eyed speculation out there. I was even sent some rather loony odds from a bookmaker that looked like this:

WHAT WILL NASA ANNOUNCE?

NASA HAS DISCOVERED A LIFE FORM ON MARS +200 33%
DISCOVERED EVIDENCE OF LIFE ON ONE OF SATURNS MOON +110 47%
ANNOUNCES A NEW MODEL FOR THE EXISTENCE OF LIFE -5000 98%
UNVEILS IMAGES OF A RECOVERED ALIEN SPACECRAFT +300 25%
CONFESSES THAT AREA 51 WAS USED FOR THE ALIEN STUDIES +500 16%

[The +/- Indicates the Return on the Wager. The percentage is the likelihood that response will occur. For Example: Betting on the candidate least likely to win would earn the most amount of money, should that happen.]

I think the bookie cleaned up on anyone goofy enough to make a bet on that.

Then the stories calmed down, and instead it was that they had discovered an earthly life form that used a radically different chemistry. I was dubious, even at that. And then I finally got the paper from Science, and I’m sorry to let you all down, but it’s none of the above. It’s an extremophile bacterium that can be coaxed into substiting arsenic for phosphorus in some of its basic biochemistry. It’s perfectly reasonable and interesting work in its own right, but it’s not radical, it’s not particularly surprising, and it’s especially not extraterrestrial. It’s the kind of thing that will get a sentence or three in biochemistry textbooks in the future.

Here’s the story. Life on earth uses six elements heavily in its chemistry: carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur, also known as CHNOPS . There are other elements used in small amounts for specialized functions, too: zinc, for instance, is incorporated as a catalyst in certain enzymes. We also use significant quantities of some ions, specifically of sodium, potassium, calcium, and chloride, for osmotic balance and they also play a role in nervous system function and regulation; calcium, obviously, is heavily used in making the matrix of our skeletons. But for the most part, biochemistry is all about CHNOPS.

i-cac37a6c74c7228f52bfa48531e329a9-chnops.jpeg

Here’s part of the periodic table just to remind you of where these atoms are. You should recall from freshman chemistry that the table isn’t just an arbitrary arrangement — it actually is ordered by the properties of the elements, and, for instance, atoms in a column exhibit similar properties. There’s CHNOPS, and notice, just below phosphorous, there’s another atom, arsenic. You’d predict just from looking at the table that arsenic ought to have some chemical similarities to phosphorus, and you’d be right. Arsenic can substitute for phosphorus in many chemical reactions.

This is, in fact, one of the reasons arsenic is toxic. It’s similar, but not identical, to phosphorus, and can take its place in chemical reactions fundamental to life, for instance in the glycolytic pathway of basic metabolism. That it’s not identical, though, means that it actually gums up the process and brings it to a halt, blocking respiration and killing the cell by starving it of ATP.

Got it? Arsenic already participates in earthly chemistry, badly. It’s just off enough from phosphorus to bollix up the biology, so it’s generally bad for us to have it around.

What did the NASA paper do? Scientists started out the project with extremophile bacteria from Mono Lake in California. This is not a pleasant place for most living creatures: it’s an alkali lake with a pH of close to 10, and it also has high concentrations of arsenic (high being about 200 µM) dissolved in it. The bacteria living there were already adapted to tolerate the presence of arsenic, and the mechanism of that would be really interesting to know…but this work didn’t address that.

Next, what they did was culture the bacteria in the lab, and artificially jacked up the arsenic concentration, replacing all the phosphate (PO43-) with arsenate (AsO43-). The cells weren’t happy, growing at a much slower rate on arsenate than phosphate, but they still lived and they still grew. These are tough critters.

They also look different in these conditions. Below, the bacteria in (C) were grown on arsenate with no phosphate, while those in (D) grew on phosphate with no arsenate. The arsenate bacteria are bigger, but thin sections through them reveal that they are actually bloated with large vacuoles. What are they doing building up these fluid-filled spaces inside them? We don’t know, but it may be because some arsenate-containing molecules are less stable in water than their phosphate analogs, so they’re coping by generating internal partitions that exclude water.

i-25707f736c4671e100e31389e7693717-GFAJ-1.jpeg

What they also found, and this is the cool part, is that they incorporated the arsenate into familiar compounds*. DNA has a backbone of sugars linked together by phosphate bonds, for instance; in these baceria, some of those phosphates were replaced by arsenate. Some amino acids, serine, tyrosine, and threonine, can be modified by phosphates, and arsenate was substituted there, too. What this tells us is that the machinery of these cells is tolerant enough of the differences between phosphate and arsenate that it can keep on working to some degree no matter which one is present.

So what does it all mean? It means that researchers have found that some earthly bacteria that live in literally poisonous environments are adapted to find the presence of arsenic dramatically less lethal, and that they can even incorporate arsenic into their routine, familiar chemistry.

It doesn’t say a lot about evolutionary history, I’m afraid. These are derived forms of bacteria that are adapting to artificially stringent environmental conditions, and they were found in a geologically young lake — so no, this is not the bacterium primeval. This lake also happens to be on Earth, not Saturn, although maybe being in California gives them extra weirdness points, so I don’t know that it can even say much about extraterrestrial life. It does say that life can survive in a surprisingly broad range of conditions, but we already knew that.

So it’s nice work, a small piece of the story of life, but not quite the earthshaking news the bookmakers were predicting.

*I’ve had it pointed out to me that they actually didn’t fully demonstrate even this. What they showed was that, in the bacteria raised in arsenates, the proportion of arsenic rose and the proportion of phosphorus fell, which suggests indirectly that there could have been a replacement of the phosphorus by arsenic.

Wolfe-Simon F,
Blum JS,
Kulp TR,
Gordon GW,
Hoeft SE,
Pett-Ridge J,
Stolz JF,
Webb SM,
Weber PK,
Davies PCW,
Anbar AD, Oremland RS (2010) A Bacterium That Can Grow by Using Arsenic Instead of Phosphorus. Science DOI: 10.1126/science.1197258.

Lungs with taste, or lungs with a fortuitous receptor?

Researchers in Maryland have discovered an interesting quirk: lung smooth muscle expresses on its surfaces a protein that is the same as the bitter taste receptor. This could be useful, since they also discovered that activating that receptor with bitter substances causes the muscle to relax, opening up airways, and could represent a new way to treat asthma. That’s a fine discovery.

But man, it really tells us something about human psychology. I’m getting all this mail right now, and just about all of it asks the same question: Why do lungs have taste receptors? What is the purpose of sensing taste with the lungs? Even the investigators speculate this way:

Most plant-based poisons are bitter, so the researchers thought the purpose of the lung’s taste receptors was similar to those in the tongue — to warn against poisons. “I initially thought the bitter-taste receptors in the lungs would prompt a ‘fight or flight’ response to a noxious inhalant, causing chest tightness and coughing so you would leave the toxic environment, but that’s not what we found,” says Dr. Liggett.

Weird. I guess the teleological impulse really is etched deep into most people’s minds. I’m going to suggest that everyone just relax, let go, and embrace a simpler assumption.

There is no purpose.

That should be our default assumption. Gene regulatory networks are complicated, with expression of all kinds of genes coupled to other genes, so my first thought was that this was a simple biological accident, and totally unsurprising. I’ve looked at enough developmental gene expression papers to know that genes get switched on and off in all kinds of complicated patterns that have nothing to do with proximal function and everything to do with the network of connections between them; sometimes if gene A is active, the only ‘purpose’ is because A is coregulated by factor X which also switches on gene B, and B is the next step in a physiological or developmental program that is adaptive for the organism.

Another way to think of it: the handle on your teapot is wobbling loose, so you bring the home toolbox into the kitchen to tighten it up with your screwdriver. Your toolbox also contains wrenches and a hammer, but we don’t speculate that the reason you brought the hammer is that you need it right then to fix the teapot. The purpose of bringing the hammer is that it’s in the same handy toolbox as your screwdriver, which is not really a purpose at all.

Now the way evolution works is that this purposeless variation may fortuitously find a purpose — a gene in the T2R family of G-protein coupled receptors is uselessly misexpressed in the lungs, but a clever doctor finds a way to take advantage of it to treat asthma, or you may spot a vagrant mouse skittering across your kitchen counter, and suddenly the hammer becomes a useful implement of pest control — but the root of that innovation isn’t purpose, but purposelessness and serendipity.

There’s another reason to be unimpressed with the purpose of the expression of this gene in the lungs. Many of you may already be familiar with another quirk of the bitter receptor — its expression is variable in people. A common observation to make in genetics labs is the existence of non-tasters, tasters, and super-tasters to a substance called phenylthiocarbamide, or PTC. The mechanism of that is variability in this same kind of receptor gene now found to be expressed in lung tissue. Shouldn’t we be used to the random element of the expression of this gene by now?

Attenborough alert

Right now on Discovery…it’s First Life with David Attenborough, which is supposed to be about the origin of life on Earth. There’s a pretty severe metazoan bias, unfortunately, so it’s really about the origin of animals, but still it’s cool stuff about the Cambrian.

So that’s why Koch funded a major evolution exhibit

I was mystified why Chief Teabagger David Koch would invest so much in a Smithsonian exhibit on human evolution — usually those knuckledraggers object to people putting their ancestry on display. An explanation is at hand, though: his big issue is denying the significance of global climate change, and the exhibit is tailored to make climate change look like a universal good.

There are some convincing examples of the subterfuge being perpetrated. There is a big emphasis on how evolutionary changes were accompanied by (or even caused by) climate shifts, which evolutionary biologists would see as almost certainly true, and so it slides right past us. But, for instance, what they do is illustrate the temperature changes in a graph covering the last 10 million years, which makes it easy to hide the very abrupt and rapid rise in the last few centuries. They also elide over an obvious fact: we’d rather not experience natural selection. Climate change may have shaped our species, but it did so by killing us, by pushing populations around on the map, by famine and disease, by conflict and chaos. Evolution happened. That doesn’t mean we liked it.

I suppose it wouldn’t leap out at an evolutionary biologist because it is true: there have been temperature fluctuations and long term changes that have hit our species hard, and nobody is denying it. However, it’s a bit of a stretch to suggest that we should therefore look forward to melting icecaps and flooding seaboards and intensified storms. It’s probably also worth pointing out that our technological civilization is certainly more fragile than anything we’ve had before. The fact that we could be knocked back to a stone age level of technology without going extinct is not a point in favor of welcoming global warming.

Now we have a new question: how did this devious agenda get past the directors of the Smithsonian?

Bad evolution

There have been no science fiction movies that I know of that accurately describe evolution. None. And there have been very few novels that deal with it at all well. I suspect it’s because it makes for very bad drama: it’s so darned slow, and worst of all, the individual is relatively unimportant and all the action takes place incrementally over a lineage of a group, which removes personal immediacy from the script. Lineages just don’t make for coherent, interesting personalities.

io9 takes a moment to list the worst offenders in the SF/evolution genre. There are a couple of obvious choices: all of Star Trek, in all of its incarnations, has been a ghastly abomination in its depiction of anything to do with biology (I think you could say the same about its version of physics). Any episode with any biological theme ought to be unwatchable to anyone with any knowledge of the basics of the field; if you turn it off whenever it talks about alien races or whenever it mentions radiation from a contrived subatomic particle, though, you’d never see a single show. Gene Roddenberry must have been some kind of idiot savant, where the “idiot” half covered all of the sciences.

I’m very pleased to see that Greg Bear’s Darwin’s Radio gets mentioned for its bad biology. That one has annoyed me for years: Bear does a very good job of throwing around the jargon of molecular genetics and gives the impression of being sciencey and modern, but it’s terrible, a completely nonsensical vision of hopeful monsters directed by viruses and junk DNA. It’s also the SF book most often cited to me as an example of good biology-based science fiction, when it’s nothing of the kind.

TimeTree

People are always asking me for the source of those nice t-shirts that illustrate how long we’ve diverged from a given species. I think the name must be hard to remember: they’re at evogeneao.com. Now there’s a little software widget that will be just as neat-o.

Look up TimeTree, and remember to show it to the kids. This is a page with a simple premise: type in the name of two taxa (it will accept common names, but may give you a list of scientific names to narrow the search), and then it looks them up in the public gene databases and gives you a best estimate of how long ago their last common ancestor lived.

Grasshoppers and I, for instance, shared a many-times-great grandpa 981 million years ago. My zebrafish and I are practically cousins, with our last shared ancestor living a mere 454 million years ago. Hey, tree, we’ve been apart for 1407 million years, how’s it going? Sparrow! Long time no see! 325 million years, huh?

You get the idea. It’s great for getting the big perspective. The kids will pester you all the time for dates. Especially since…it’s got an iPhone app! Get on the App Store on your smart phone or iPad and search for TimeTree — it’s totally free (except for the cost of owning such a gadget, of course).

Oh, and once you’re done entertaining the children and yourself, it’s actually a serious tool. Tap on the results and it’ll take you to all the scientific details: breakdown of mitochondrial vs. nuclear date estimates, source papers, all that sort of thing.

For details on how it works, there’s also a published paper:

Hedges SB, Dudley J, Kumar S (2006) TimeTree: a public knowledge-base of divergence times among organisms. Bioinformatics 22(23):2971-2972.

Look, a cat! 92 million years.

Curl up and die already, HuffPo

Jebus, but I despise that fluffy, superficial, Newagey site run by the flibbertigibbet Ariana. I will not be linking to it, but if you must, you can just search for this recent article: “Darwin May Have Been WRONG, New Study Argues”. I don’t recommend it. It sucks. Read the title, and you’ve already got the false sensationalism of the whole story down cold.

It’s actually an old and familiar story that doesn’t upset any applecarts at all. There is a well-known concept in evolutionary theory of an adaptive radiation: a lineage acquires a new trait (birds evolve flight, for instance), or an extinction removes all competition and creates an opportunity for expansion (the dinosaurs are wiped out and mammals expand rapidly into vacant niches), and presto, new species and diversity abounds. For a really obvious example of this phenomenon, look to Darwin’s finches: one or a few species are storm-blown to an isolated chain of islands, and they gradually speciate to take on many roles.

See? No shock, no strike against evolution, or even against Darwin’s version of evolution. To claim otherwise is simply stupid.

Now the paper in question seeks to quantify the expansion of taxonomic diversity with the appearance of large-scale ecological opportunities, and concludes that competition and refinement by natural selection has not been the major driver of diversification, but that reason we have thousands of species of mammals and even more species of birds is more a consequence of chance and opportunity than strong competition. It’s a reasonable result, but not cause for a revolution; lots of us have been advocating for the importance of chance in evolution for many years, and it’s unsurprising that non-selective mechanisms of evolution will generate new diversity from a single species in an open, competition free field.

Bugger the awful Huffpo. One of the scientists, Sarda Sahney, has a nice blog with a sensible discussion of the paper. Read that instead.

It’s more than genes, it’s networks and systems

i-e88a953e59c2ce6c5e2ac4568c7f0c36-rb.png

Most of you don’t understand evolution. I mean this in the most charitable way; there’s a common conceptual model of how evolution occurs that I find everywhere, and that I particularly find common among bright young students who are just getting enthusiastic about biology. Let me give you the Standard Story, the one that I get all the time from supporters of biology.

Evolution proceeds by mutation and selection. A novel mutation occurs in a gene that gives the individual inheriting it an advantage, and that person passes it on to their children who also gets the advantage and do better than their peers, and leave more offspring. Given time, the advantageous mutation spreads through the population so the entire species has it.

One example is the human brain. An ape man millions of years ago acquired a mutation that made his or her brain slightly larger, and since those individuals were slightly smarter than other ape men, it spread through the population. Then later, other mutations occured and were selected for and so human brains gradually got larger and larger.

You either know what’s wrong here or you’re feeling a little uneasy—I gave you enough hints that you know I’m going to complain about that story, but if your knowledge is at the Evolutionary Biology 101 level, you may not be sure what it is.

Just to make you even more queasy, the misunderstanding here is one that creationists have, too. If you’ve ever encountered the cryptic phrase “RM+NS” (“random mutation + natural selection”) used as a pejorative on a creationist site, you’ve found someone with this affliction. They’ve got it completely wrong.

Here’s the problem, and also a brief introduction to Evolutionary Biology 201.

First, it’s not exactly wrong — it’s more like taking one good explanation of certain kinds of evolution and making it a sweeping claim that that is how all evolution works. By reducing it to this one scheme, though, it makes evolution far too plodding and linear, and reduces it all to a sort of personal narrative. It isn’t any of those things. What’s left out in the 101 story, and in creationist tales, is that: evolution is about populations, so many changes go on in parallel; selectable traits are usually the product of networks of genes, so there are rarely single alleles that can be categorized as the effector of change; and genes and gene networks are plastic or responsive to the environment. All of these complications make the actual story more complicated and interesting, and also, perhaps to your surprise, make evolutionary change faster and more powerful.

Think populations

Mutations are the root of biological variation, of course, but we often have a naive view of their consequences. Most mutations are neutral. Even advantageous mutations are subject to laws of chance in their propagation, and a positive selection coefficient does not mean there will be an inexorable march to fixation, where every individual has the allele. This is also true of deleterious mutations: chance often dominates, and unless it is a strongly negative allele, like an embryonic lethal mutation, there’s also a chance it can spread through the population.

Stop thinking of mutations as unitary events that either get swiftly culled, because they’re deleterious, or get swiftly hauled into prominence by the uplifting crane of natural selection. Mutations are usually negligible changes that get tossed into the stewpot of the gene pool, where they simmer mostly unnoticed and invisible to selection. Look at human faces, for instance: they’re all different, and unless you’re looking at the extremes of beauty or ugliness, the variations simply don’t make much difference. Yet all those different faces really are the result of subtly different combinations of mutant forms of genes.

“Combinations” is the magic word. A single mutation rarely has a significant effect on a feature, but the combination of multiple mutations may have a detectable or even novel effect that can be seen by natural selection. And that’s what’s going on all the time: the population is a huge reservoir of genetic variation, and what we do when we reproduce is sort and mix and generate new combinations that are then tested in the environment.

Compare it to a game of poker. A two of hearts in itself seems to be a pathetic little card, but if it’s part of a flush or a straight or three of a kind, it can produce a winning hand. In the game, it’s not the card itself that has power, it’s its utility in a pattern or combination of other cards. A large population like ours is a great shuffler that is producing millions of new hands every day.

We know that this recombination is essential to the rapid acquisition of new phenotypes. Here are some results from a classic experiment by Waddington. Waddington noted that fruit flies expressed the odd trait of developing four wings (the bithorax phenotype) instead of two if they were exposed to ether early in development. This is not a mutation! This is called a phenocopy, where an environmental factor induces an effect similar to a genetic mutation.

What Waddington did next was to select for individuals that expressed the bithorax phenotype most robustly, or that were better at resisting the ether, and found that he could get a progressive strengthening of the response.

i-b7d71dfe023865cd8212e074b3e018b3-bithorax.jpeg
The progress of selection for or against a bithorax-like response to ether treatment in two wild-type populations. Experiments 1 and 2 initially showed about 25 and 48% of the bithorax (He) phenotype.

This occurred over 10s of generations — far, far too fast for this to be a consequence of the generation of new mutations. What Waddington was doing was selecting for more potent combinations of alleles already extant in the gene pool.

This was confirmed in a cool way with a simple experiment: the results in the graph above were obtained from wild-caught populations. Using highly inbred laboratory strains that have greatly reduced genetic variation abolishes the outcome.

Jonathan Bard sees this as a powerful potential factor in evolution.

Waddington’s results have excited considerable controversy over the years, for example as to whether they reflect threshold effects or hidden variation. In my view, these arguments are irrelevant to the key point: within a population of organisms, there is enough intrinsic variability that, given strong selection pressures, minor but existing variants in a trait that are not normally noticeable can rapidly become the majority phenotype without new mutations. The implications for evolution are obvious: normally silent mutations in a population can lead to adaptation if selection pressures are high enough. This view provides a sensible explanation of the relatively rapid origins of the different beak morphologies of Darwin’s various finches and of species flocks.

Think networks

One question you might have at this point is that the model above suggests that mutations are constantly being thrown into the population’s gene pool and are steadily accumulating — it means that there must be a remarkable amount of genetic variation between individuals (and there is! It’s been measured), yet we generally don’t see most people as weird and obvious mutants. That variation is largely invisible, or represents mere minor variations that we don’t regard as at all remarkable. How can that be?

One important reason is that most traits are not the product of single genes, but of combinations of genes working together in complex ways. The unit producing the phenotype is most often a network of genes and gene products, such at this lovely example of the network supporting expression and regulation of the epidermal growth factor (EGF) pathway.

i-6da181d843f908cf8ac30e2218f723b9-egf_network.jpeg
The EGF pathway (from www.sabiosciences.com/pathwaycentral.php)

That is awesomely complex, and yes, if you’re a creationist you’re probably wrongly thinking there is no way that can evolve. The curious thing is, though, that the more elaborate the network, the more pieces tangled into the pathway, the smaller the effect of any individual component (in general, of course). What we find over and over again is that many mutations to any one component may have a completely indetectable effect on the output. The system is buffered to produce a reliable yield.

This is the way networks often work. Consider the internet, for example: a complex network with many components and many different routes to get a single from Point A to Point B. What happens if you take out a single node, or even a set of nodes? The system routes automatically around any damage, without any intelligent agency required to consciously reroute messages.

But further, consider the nature of most mutations in a biological network. Simple knockouts of a whole component are possible, but often what will happen are smaller effects. These gene products are typically enzymes; what happens is a shift in kinetics that will more subtly modify expression. The challenge is to measure and compute these effects.

Graph analysis is showing how networks can be partitioned and analysed, while work on the kinetics of networks has shown first that it is possible to simplify the mathematics of the differential equation models and, second, that the detailed output of a network is relatively insensitive to changes in most of the reaction parameters. What this latter work means is that most gene mutations will have relatively minor effects on the networks in which their proteins are involved, and some will have none, perhaps because they are part of secondary pathways and so redundant under normal circumstances. Indirect evidence for this comes from the surprising observation that many gene knockouts in mice result in an apparently normal phenotype. Within an evolutionary context, it would thus be expected that, across a population of organisms, most
mutations in a network would effectively be silent, in that they would give no selective advantage under normal conditions. It is one of the tasks of systems biologists to understand how and where mutations can lead to sufficient variation in networks properties for selection to have something on which to act.

Combine this with population effects. The population can accumulate many of these sneaky variants that have no significant effect on most individuals, but under conditions of strong selection, combinations of these variants, that together can have detectable effects, can be exposed to selection.

Think flexible genes

Another factor in this process (one that Bard does not touch on) is that the individual genes themselves are not invariant units. Mutations can affect how genes contribute to the network, but in addition, the same allele can have different consequences in different genetic backgrounds — it is affected by the other genes in the network — and also has different consquences in different external environments.

Everything is fluid. Biology isn’t about fixed and rigidly invariant processes — it’s about squishy, dynamic, and interactive stuff making do.

Now do you see what’s wrong with the simplistic caricature of evolution at the top of this article? It’s superficial; it ignores the richness of real biology; it limits and constrains the potential of evolution unrealistically. The concept of evolution as a change in allele frequencies over time is one small part of the whole of evolutionary processes. You’ve got to include network theory and gene and environmental interactions to really understand the phenomena. And the cool thing is that all of these perspectives make evolution an even more powerful force.

Bard J (2010) A systems biology view of evolutionary genetics. Bioessays 32: 559-563.