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

How old is old, part II: 3465...and counting!

Early life
How old is old?  We asked this question on Monday when it came to relate to human evolution and our species' age and history as revealed by genetic data, in light of new estimates of the genetic mutation rate.  Here, we're talking about differences of around 1 million or so years since we evolved from chimps, or much less since modern humans diverged from our barbarous colleagues like Neandertals.

We see some modest changes in less than 10 million years, and debate whether it was 10 million or 'only' 7.  But let's put that in perspective.

The really early life
A former college classmate of mine, Bill Schopf, at UCLA, has been one of the discoverers of the earliest of early life, the first fossils of life that are found on earth.  These are bacterial colony constructs.  Some are organized in compacted layers, known as stromatolites.  The structures resemble modern stromatolites, and they and other structures of fossil bacteria bear remarkable resemblance to today's bacteria and their biofilms, modern day versions of fossil stromatolites.  How old are they?  A mere 3465 Million, that is 3.465 billion years!

A recent report by Schopf and Anatoliy Kudryatsev, in the journal Gondwana Research (Gondwana is the name for the earliest continent), reports on modern tests to show definitively that these fossils are real, as this as been the subject of some debate.  Here are images of these fossils and of their bacterial structures found from that report. After many years of various types of highly technical tests, the internal details as well as external shape and cellular structures now seem convincing that these are not natural mineral formations, but really are evidence of life.

The earth itself is estimated to be 4.54 Bya.  This means that from the first fireball, to life's first primordial 'soup' essentially to modern bacteria took only 1 Billion years.  If bacteria and their aggregations were very primitive, or just barely making it as living organisms, then one might say that's about what we'd expect: a billion years to make the first staggering living things.  But these are, in a reasonable sense of the word, already modern.

One has to assume that their genomes would be very different from bacterial genomes today.  If you look at genetic divergence among bacteria and other comparably primitive forms of life, you see that they are as different as you'd expect for such an old beginning....that is, they have diverged by an amount consistent with the 3+ billion year common ancestry. There is a touch of circularity in species split-time estimates because they are calibrated by fossil and other geological dating.  But the picture is consistent.

What this means is that the morphology, to a great extent, has been conserved for aeons of time, a rather remarkable fact, given that other descendants have diverged hugely, leading to plants, and us!  How we can explain this  level of conservation of structure, given the divergence of genomes, is a major but largely unrecognized challenge for evolutionary genetics.

These findings make it seem trivial to ask how a few hundred million year old arthropods, like horseshoe crabs, or ancient but much more recent fossil insects or fish, can appear to be so highly conserved, if evolution is a relentless rat-race to adapt to a competitive and changing environment.

The environments on earth are always changing, even if gradually and with some long-term stability.  One can imagine that once adapted to an environment, it may be risky for a mutant organism to survive, if most mutations, occurring randomly with respect to function, are more likely to cause harm than to be beneficial.  But since so much life is no longer bacterial and since there are so many  kinds of bacteria, do we have a serious question to ask how any recognizable morphology of this nearly earliest of life could have persisted so long--when their descendant genomes as a whole, even among bacteria, have diverged in a reasonably molecular clock-like way?

One would expect drift to occur in many, if not all traits: small, gradual changes that didn't harm fitness but that accumulated over billions of years to make the founding forms basically unrecognizable. Apparently this is not the case.  Thinking about how to explain that is interesting--at least as interesting as accounting for Neandertal vs modern human variation and evolution.

How old is 'old'?

A story in last Friday's Science by Ann Gibbons concerns various recent, direct estimates of the DNA mutation rate in humans, and its import for the way we reconstruct our geographic and demographic origins.  The point is that new estimates are that mutations, nucleotide by nucleotide each generation, occur only about half as frequently as earlier estimates.  Instead of about one per 100 million nucleotides the estimates are about twice that.  How could numbers so small have any import at all?

The timing of various aspects--here we'll loosely call them 'events' even if they occurred very gradually in human lifetime terms--of human prehistory is at issue.  When we look at human variation today, and compare it to that in other primates, we try to account for how rapidly new variation arises.  If we take into account estimates of population size, the rate of new mutation is counterbalanced by loss due to chance, and the amount of standing variation within our population, or of difference from our nearest relatives, can be used to estimate the timing of expansions and migrations and geographic variation within our own species, when we diverged from those earlier relatives as a new species, and when/where/if we split into sub-groups (like Neandertals) that then interbred or became extinct.

The standard story had been that we diverged from chimps about 6-7 million years ago (Mya), and that the Neandertal group had started 400 thousand years (Kya) or so.  New direct estimates of mutation, on the order of 1 per 10^8 nucleotides, are slower and hence imply longer time periods for these inferred events in our history.

That would make no important difference, unless thinking that humans diverged from chimps 9 rather than 7 million years ago matters to you.  That's rather abstract, at best.  But there is some import in these estimates.

They are not fixed in stone, either in terms of their accuracy as averages from relatively sparse data (for example, mutation rates vary along the genome and between individuals), or over historical time and environments.  The per-year rates involve body size and hence generation length, and may have differed in the past.  The mating pattern may matter, since older males have had more sperm-line cell divisions in which mutation can have occurred, so populations with, say, older dominant males mating more often will have higher mutation rates per generation.  And so on.

But things really matter most when it comes to being consistent with the fossil record.  Fossils have tended to suggest more recent event times, and mutation rates that are often based on such times as calibrating points have been fitted accordingly, at least in part.  Of course, by the time morphology shows recognizable species differences, the species have already been clearly split for an unknown length of time.  Likewise gene-based separation times usually underestimate actual isolation events, for well-known reasons.

If, for example, we now don't know when human ancestors and/or Neandertals left Africa, our estimates of their history of admixture (or not) will be affected.  They could not have admixed if they hadn't evolved or emerged from Africa!  Right now, paleontologists are not easily agreeing with revised mutation rate estimates, but clearly the two kinds of data must be brought into agreement.

Probably, there will be little difference in the overall picture we get from fossil and genetic data on past and present variation.  The times will matter.  If that leads to other issues, they will have to be faced.

The issues arise because we're getting better data from genomic sequences, so they are legitimate--they are not just stubborn food fights among different research groups.  Whether they will make any substantial difference in our understand of our evolution as a species seems less likely, but remains open.