If mutations can go viral, adaptationism is less annoying.

Feb. 9, 2016: I have edited the paragraph beginning with "Exciting..." to remove details of mutation rates because my initial posting was probably wrong about coding vs. non-coding mutation rates. To fix that requires much more nuance than is relevant for the point I'm making in that paragraph, not to mention much more nuance than I'm capable of grasping immediately! Cheers and thanks to Daniel and Ken in comments below and to everyone who chimed in on Twitter. 

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I always account for virally-induced mutation when I imagine the evolution of our genome. That's because I'll never forget this quote. Who could?

“Our genome is littered with the rotting carcasses of these little viruses that have made their home in our genome for millions of years.” - David Haussler in 2008 

Or this...

"Retroviruses are the only group of viruses known to have left a fossil record, in the form of endogenous proviruses, and approximately 8% of the human genome is made up of these elements." (source and see this)

Exciting virus discoveries aside, we're constantly mutating with each new addition to the human lineage. Thanks to whole genome sequencing, the rate of new mutation between human parent and offspring is becoming better known than ever before. We each have new single nucleotide mutations in the stretches of our DNA that are known to be functional (very little of the entire genome) and that are not (the majority of the genome). These are variants not present in our parents’ codes (for example, we might have a ‘T’ where there is a ‘A’ in our mother’s code). And there are also deletions and duplications of strings of letters in the code, sometimes very long ones. Estimates vary on parent-offspring mutation rate and that's because there are different sorts of mutations and individuals vary, even as they age, as to how many mutations they pass along, for example. Still, without any hard numbers (which I've left out purposefully to avoid the mutation rate debate), knowing that there is constant mutation is helpful for imagining how evolution works. And it also helps us understand how mutations even in coding regions aren't necessarily good nor bad. Most mutations in our genome are just riding along in our mutation-tolerant codes—where they will begin and where they will go no one knows!

And it's with that appreciation for constant, unpredictable, but tolerated mutation—of evolution's momentum, of a lineage's perpetual change, selection or not—on top of a general understanding of population genetics that just makes adaptation seem astounding. It makes it difficult to believe that adaptation is as common as the myriad adaptive hypotheses for myriad traits suggest.

That's because this new raw material for adaptation, this perpetual mutation, really is only a tiny fragment of everything that can be passed on. But, what's more, each of those itty bitty changes could be stopped in its tracks before going anywhere.

The good, the bad, and the neutral, they all need luck to pass them onto the next generation. That's right. Even the good mutations have it rough. Even the winners can be losers! Here are the ways a mutation can live or die in you or me:

The Brief or Wondrous Life of Mutations, Wow.

This view of mutation fits into that slow and stately process that Darwin described, despite his imagination chugging away before he had much understanding of genetics.

Of course, bottlenecks or being part small populations would certainly help our rogue underdogs proliferate, and swiftlier so, in future generations.

Still, trying to imagine how any of my mutations, including any that might be adaptive, could become fixed in a population is enough to make me throw Origin of Species across the room.

By "adaptive," I'm talking about "better" or "advantageous" traits and their inherited basis ... that ever-popular take on the classic Darwinian idea of natural selection and competition.

For many with a view of mutation like I spelled out above, it's much easier to conceptualize adaptation as the result of negative selection, stabilizing selection, and tolerant or weak selection than it is to accept stories of full-blown positive selection, which is what "Darwinian" usually describes (whether or not that was Darwin's intention). One little error in one dude's DNA plus deep time goes all the way to fixed in the entire species because those who were lucky enough to inherit the error passed it on more frequently, because they had that error, than anyone passed on the old version of that code? I guess what I'm saying is, it's not entirely satisfying.

But what if a mutation could be less pitiful, less lonely, less vulnerable to immediate extinction? Instead, what if a mutation could arise in many people simultaneously? What if a mutation didn't have to start out as 1/10,000? What if it began as 1,000/10,000?

That would certainly up its chances of increasing in frequency over time, and quickly, relative to the rogue underdog way that I hashed out in the figure above. And that means that if there was a mutation that did increase survival and reproduction relative to the status quo, it would have a better chance to actually take over as an adaptation. This would be aided, especially, if there was non-random mating, like assortative mating, creating a population rife with this beneficial mutation in the geologic blink of an eye.

But how could such a widespread mutation arise? This sounds so heartless to put it like this, but thanks to the Zika virus, it seems to me that viruses could do the trick.

Electron micrograph of Zika virus. (wikipedia)

I'd been trapped in thinking that viruses cause unique mutations in our genomes the way that copy errors do. But why should they? If they infect me and you, they could leave the same signatures in our genomes. And the number of infected/mutated could increase if the virus is transmitted via multiple species (e.g. mosquito and human, like Zika). If scientists figure out that the rampant microcephaly associated with the Zika virus is congenital, wouldn't this be an example* of the kind of large-scale mutation that I'm talking about? 

*albeit a horrifying one, and unlikely to get passed on because of its effects, so it's not adaptive whatsoever.

If viral mutations get into our gametes or into the stem cells of our developing embryos, then we've got germ-line mutation and we could have the same germ-line mutation in the many many genomes of those infected with the virus. As long as we survive the virus, and we reproduce, then we'll have these mutant babies who don't just have their own unique mutations, but they also have these new but shared mutations and the shared new phenotypes associated with them, simultaneously.

Why not? Well, not if there are no viruses that ever work like this.

We need some examples. The mammalian placenta, and its subsequent diversity, is said to have begun virally, but I can't find any writing that assumes anything other than a little snowflake mutation-that-could.

Anything else? Any traits that "make us human"? Any traits that are pegged as convergences but could be due to the mutual hosting of the same virus exacting the same kind of mutation with the same phenotypic result in separate lineages?

I've always had a soft spot for underdogs. And I've always given the one-off mutation concept the benefit of the doubt because I know that my imagination struggles to appreciate deep time. What choice do you have when you think evolutionarily? However, just the possibility that viruses can mutate us at this larger scale, even though I know of no examples, is already bringing me a little bit of hope and peace, and also some much needed patience for adaptationism.

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Update: I just saw this published today, asking whether microcephaly and other virus-induced birth defects are congenital. Answer = no one knows yet: http://www.nytimes.com/2016/02/09/science/zika-virus-microcephaly-birth-defects-rubella-cytomegalovirus.html?partner=IFTTT&_r=1

Censorship in science won't go viral

The BBC radio program, Inside Science, recently considered the issue of research into how viruses become transmissible between humans and whether it should be allowed.  What enables viruses to, well, go viral--to be able to spread rapidly among the population with devastating consequences?  We think of war as devastating but until recently more, or far more, combatants died from sickness than from battle injuries.  The 1918 flu pandemic is iconic for this, but millions have died in miserable obscurity in army camps or just at home, over the years.

From time to time viral diseases erupt, often from animal reservoirs, to be transmissible to, and most dangerously among, humans.  As we try to combat pathogens, we face both antibiotic resistance in bacteria and the demography of human population, crowding, and travel that contributes to viral epidemics.

Many of the worst viruses primarily live in nonhuman animal hosts.  There, they can transfer from individual to individual and may not even be very virulent.  But if particular mutations arise that allow them to not only infect a human host, but be transferred between them, then we have an epidemic.

While some viral genes have been identified in strains that lead to human epidemics, no gene has been identified that enables the human-to-human transfer.  Preventing that could stop an epidemic in its tracks, so could be very important to global health.  So about a year ago, investigators in the Netherlands announced research findings that had identified some genetic basis for such transfer.

This raised a furor.  The idea was to use genomic techniques to introduce mutations and screen for ones that enabled a flu virus to be transmitted from human to human (well, experimentally it was among ferrets, who are a good model for human flu virus transfer).  That that work was even being done terrified many, because enabling a virus to become infectious in that way could, if the virus were to escape the lab, conceivably cause a global pandemic.  Indeed, terrorists could use such a thing to great harm.

A yearlong moratorium against publishing or even doing this kind of research was suggested and at least partly followed.  But the moratorium has ended, with little resolution about the kind of work and how, where, or whether it should be done.  Scientists doing the work defend it, of course, even if acknowledging some slight risk that the engineered virus could escape.  But the justification is that the risk is small and that viral pandemics are inevitably in our future just because of mutation and selection in nature, and that this research could teach us enough to somehow anticipate or prevent such outbreaks.

Should we worry that a terrorist might learn the techniques from that public-spirited scientific literature and create devastation in his basement lab? One of the guests on the show said that the risk is so slight that it shouldn't be a consideration.  That isn't even the right question, I don't believe.  It isn't wild-catting individuals, but nation states, or groups funded by them, who would be most likely to engineer viral mayhem for political or military purposes.

The Snowden  Factor
Given the history of leaked secrets, or Snowden-like leaking of the existence of secrets, that has taken place in recent history, this isn't far-fetched.  Of the many workers, from students to faculty to who knows who else, who would be involved in viral engineering experiments, or the scientists with government funds who read Nature and learn what you need to start up a lab of this type, does anyone think it is all that unlikely that if not other countries, at least some disgruntled worker or one whose politics differ from the host lab director's, etc., would take the secrets to some highest bidder?  The risks should not be minimized. And, of course, if one thinks of the Snowden factor, which hostile governments (who can also read Nature) might already be up to this kind of stuff, for military or geopolitical, or even defensive purposes? 

The Pandora's box argument
A common rationale scientists give for not having their work hands tied is that science is about nature, and if we don't investigate some subject somebody else will, so let us just carry on.  It's government's job to prevent abuse, isn't it?  This is the selfish argument, whether or not there is anything malicious behind it in an individual case.  But society does have the right and the precedent for keeping Pandora's box closed.  At least to some, if highly inadequate extent, our institutional review boards (IRBs) have to approve all university and government research before it can be done.  And while torture is in fact visited on countless laboratory animals with the IRBs' blessings, they do at least prohibit some things.   You can't put toxin in dining hall food to see how any people get sick, not even if you were to get students' permission first.  Science is, in some minimal sense at least, already censored.  We are not morally required to recognize that the world is out there, and anything some scientist wants to know about it is fair game.

Yet the problems are real, and maybe science can help
Greedy and self-interested as we scientists are, it is only proper to recognize that many of us are not in it just for the money.   We have a sometimes compulsive and relentless desire to understand and ameliorate problems of the world.  Viral epidemics, that could be lethal to millions or more, certainly qualify.  Scientists aren't just venal for grants, we need them to pay for our staff and equipment and so on.  We are imperfect and follow fads, but our methods are not just faddish but often do work in ways we hope.  We have a lot of understanding of genes, pathogen-host evolution, and epidemiology to be able to understand problems like we're discussing and often we can, indeed, do something about them.

So if we don't let scientists do this, we prevent what they might achieve.  We should not stifle their work for trivial reasons.