Wednesday, July 18, 2018

Deep Genetics

First, a note about the title.  Many years ago Bill Gates mentioned somewhere that he had learned a lot by studying something called "deep history".  It turns out that the name comes from an idea popularized by Daniel Lord Smail, a Harvard History professor.  I took a video version of a course on the subject that used to be offered through a company called "Great Courses".  Sad to say, it looks like they no longer offer it.  But the course gave me a chance to see what Gates was talking about and I was grateful for the experience.  So what kind of history is "deep" history?

Let's start out with what "history" is.  (And, yes, there is a precise definition of the word.)  History is what people have written about what happened, about people and events.  The key idea is that history is written.  If it's not in a book its not history.  That means "history" covers at most 3,000 years and often far less.  We have histories written by ancient Romans, Greeks, Egyptians, Chinese, etc.  Writing has to have been invented and someone has to have written specifically about events, past and present.

Writing that goes beyond business and tax records hasn't been around for very long.  It is necessary that people engage in this more broad type of writing (and for their work effort to be preserved) for a particular historic record to exist.  And these early historians tended to make things up when they were writing about events that had not happened in the recent past.  So we get, for instance, an entirely mythological description of how and by whom the city of Rome was founded.  But even allowing for this, early histories typically did not venture far back into the past.

What precedes history is archeology. You dig things up and try to figure out what happened and who was involved.  For a long time what archeologists mostly dug up was bones.  The rest was mostly stuff people made like pots and jewelry.  Archeology allows us to study much more of the past.  But archeology as most people envision it (i.e. Indiana Jones digging up stuff) only takes us back so far.  And that "so far" is to something called the "Cambrian Explosion".

Consider most people's idea of an archeological "dig".  A relatively small piece of land is carefully excavated and every interesting object is located, examined, catalogued, and later studied.  How are interesting objects located?  People see them poking out of the ground.  And the important thing about this is that people see them.  The object is large enough to be visible with the naked eye.  It turns out that all life forms that are big enough to be seen with the naked eye date from the Cambrian Explosion or later.  But the Cambrian Explosion happened in round numbers 500,000 years ago.  That sounds like a long time but the earth is 4.54 billion years old.  (This number is known to be correct within an accuracy of  plus or minus 1%.)  So what happened in the intervening 4 billion years?

Interesting question.  And it's one that science has only a general idea of what the answer is.  So let's ask a related question.  How long has life existed on earth?  Here too science has only a general idea.  The best guess (and at this point, it's a guess) is that life has existed on earth for between 3.77 and 4.28 billion years.  So why is it a guess?  And why is the range so large?  The problem is a simple one.  We are trying to positively identify the remains of tiny single celled creatures.  They are quite fragile, have no bones, and are tiny.  This means they leave no trace of themselves behind except in extremely extraordinary and extremely unusual situations.  Finding a needle is a haystack (magnet, anyone?) is a piece of cake in comparison.

As a result the first really solid evidence for life involved finding the mineralized (i.e. fossilized) remains of a single celled microorganism in a kind of rock called "Apex chert" in a formation in Australia.  It has been dated to 3.564 billion years ago.  But the microorganism in question looks pretty complicated.  So scientists speculate that it's predecessors stretch back a short (i.e. to 3.77 billion years ago) or a long (i.e. to 4.28 billion years ago) time.  In any case, it appears that it took less than a billion years for life to originate on earth.  And it appears that not much happened between then and 3 billion years later when the Cambrian Explosion happened.

Before going further let me take a small side trip.  What's with this whole Cambrian Explosion thing, and specifically, what's with the whole "explosion" business?  Glad you asked.  As far as anyone can tell all life was composed of single celled creatures until about 800,000 years ago.  Then something happened and multi-celled creatures appeared seemingly instantly.  They quickly diverged into many different forms.  But these early creatures were still too small to be seen by the naked eye.  And, more importantly, they didn't have bones or shells.  That made them hard to find, especially if you weren't looking very carefully for them.

Then in another "blink of an eye" moment shells and bones and other stuff that gets preserved in sediment started showing up.  And the creatures with the bones, shells, etc. were big enough to be seen by the naked eye.  This point where geologists and archeologists went from "just rock" to "rock with all kinds of wee beasties in it" seemed to scientists of the time to be like an explosion.  They went from no life to all kinds of life (and lots of it looking truly weird) in an instant.  Life exploded into existence.

The Cambrian explosion is usually dated to 541 million years ago.  I used 500,000 above because it is a round number that is close enough for my purposes.  (The same thing is true for my 800,000 number.)  It didn't take long for broad speculation to emerge that there was something before the Cambrian explosion.  And careful study found the multi-celled predecessors of the critters that "seemingly sprang from nowhere".  And thus the explosion was explained.  Lots of life had been around for a while.  It just turned out that in many cases it all of a sudden evolved into the kinds of creatures that can be identified by careful "naked eye" examination.  So it was pretty easy to trace all the variety of life that first appeared during the explosion to earlier life and to trace this earlier life back to single celled creatures.

But that still left the question of what happened between roughly 3.5 billion years ago and roughly 0.5 billion years ago?  And that parallels the approach that the "deep history" lectures took.  Instead of confining themselves to history, the last 3,000 years, the lectures went back to the origin of life on earth.  And, in fact, they went all the way back to the origin of the known universe 13.8 billion years ago.  I don't want to go that far back.  So I am going to focus on the period between 3.5 (roughly) billion years ago and 0.5 (roughly) billion years ago.  And I am going to focus on the evolution of life during this period.

Science knows very little about this time period.  The problem is that what survives of life from this period doesn't tell us much.  Each creature is microscopic and nothing of the actual creature survives.  What does survive can be described as a shadow.  All the chemicals that originally made up the creature are replaced by minerals.  The minerals often start out as liquids but solidify over time leaving the traces we can now dig up and examine.  It would be nice to have DNA from these creatures.  But DNA is a very fragile chemical when subjected to vast amounts of time and to geological processes.

Scientists have become adept at recovering DNA from bones and teeth that are thousands of years old.  But that gets us back only about as far as history gets us.  Various creatures get stuck in amber.  Some DNA from creatures that are tens of thousands of years ago can sometimes be recovered because the amber provides a very stable and protective environment.  That gets us farther back to the most recent part of the archeological period.  The conceit behind the "Jurassic Park" movie was that DNA from tens of millions of years ago could be recovered and used to build dinosaurs.  If this were possible that would gets much deeper into the archeological period.

It seems unlikely this will ever be possible.  And remember, we are now talking about hundreds of millions of years.  We want to get to billions of years back.  It is unlikely in the extreme that DNA from this far back will ever be available.  And the same is true for the other chemicals that make up cells.  It is unlikely that it will ever be able to study anything except the shadow of these creatures.

So scientists have only two sources of information.  First, they get a limited amount of shape information from the shadow in the rock that is all that is left.  The other information is environmental.  The early atmosphere of the earth was quite different than it is now.  At one point vast quantities (billions of tons) of Sulfur precipitated out and formed vast deposits in the earth.  The same thing later happened with Iron.  Most modern life forms can not survive in environments where there is too much Iron or Sulfur.

And we now separate life into plants and animals.  Plants take up Carbon Dioxide and excrete Oxygen.  Animals take up Oxygen and excrete Carbon Dioxide.  Animals could not come into existence until Oxygen came to make up a significant portion of the atmosphere.  And many animals, humans included, can't survive if the atmosphere contains even 1% Carbon Dioxide.  So almost all of the Carbon Dioxide was scrubbed from the atmosphere at some point.  We know this because we know the early atmosphere of the earth contained a lot of Carbon Dioxide.

Life optimizes itself to survive in a particular environment.  So early life was well set up to handle the environment of that period (lots of Carbon Dioxide and other stuff no longer present, no Oxygen and lots of other stuff now present).  It also had to be able to thrive in a general environment containing lots of Sulfur and Iron, just to mention two obvious differences.  How did life of the time do that?  We just don't know.

But those are specific adaptations and I am interested in more general ones.  There seems to be no reason that whatever allowed early single cell organisms to survive lots of Carbon Dioxide, Sulfur, Iron, etc. and little or no Oxygen, etc. from becoming multicellular (and large).  But they didn't.  Why?

When one is discussing evolution the phrase "survival of the fittest" is often bandied around.  It is generally assumed to be vaguely negative.  Only mean beasties with no morals and big teeth need apply.  But that is not at all the situation.  There is no time in the entire period where life existed on the earth when single celled creatures have not been the dominant life form in terms of numbers (or even in terms of aggregate mass).  Lions seem fitter to survive.  But there are only a few Lions.  There used to be more but not so many more that you could add their total weight together and get a total weight that was greater than that of all the green algae in the ocean.  If you go by numbers instead mass the margin favoring green algae is far greater.  Either way, the algae win.

An organism in order to be "fit to survive" need only be as good as or better than its immediate competition.  So a particular strain of green algae need only be worried about being as fit as or fitter than other strains of green algae.  It also needs to be able to thrive well enough so that after all the other critters that eat it have dined there are lots of green algae left.  And my larger point is that Lions and green algae are not in competition with each other.  The green algae is much better at being a green algae than a Lion would be.  The Lion is much better at being a Lion than the green algae would be.  They are pretty much oblivious to each other.

But taking the long view, somehow a green algae-like single celled creature evolved into a multi-cellular Lion.  But that's just the context.  The question I want to focus on is why did some single cell creatures evolved into multicell creatures (and eventually into Lions) when for billions of years they didn't.  I have a guess.

For a long time there was a theory that there was a long term evolutionary trend toward complexity.  People went further.  They said "complex is better" and by "better" they meant fitter.  But a careful study found lots of examples of more complex giving way to less complex and the less complex creatures surviving and thriving.  To provide but one example, some fish survive in caves where they are cut off from all light.  Over generations they lost the ability to see.  The complex eye (and the visual system that backs it) deteriorates and eventually disappears.  The reason is simple.  Eyes (and eyesight) exact a cost.  If eyes and eyesight don't provide a benefit it makes fish with eyes less fit and they get beat out by more fit fish without eyes.

I want to turn this thinking inside out.  But I am going to do it in steps.  In general eyes are very helpful.  That's why almost all animals have them.  And animals have evolved to the point where they have all the machinery necessary to make eyes.  In most situations eyes add complexity but they allow an animal to respond to its environment in more and more complex ways than an animal without eyes.  So the presence of the eye (and its supporting vision system) makes the animal more fit.  But even in this situation things are more complex.

Some animals (eagles) have very good eyes while others (people) have eyes that are not so good.  I want to emphasize the relatively of the concept of "survival of the fittest".  Complexity in general and good eyesight in particular do not always contribute positively to fitness.  An animal with poorer eyesight can be more fit than another animal with good eyesight.  Perhaps the "less fit" animal has other different attributes that are more important and more than make up for the poor eyesight.  You have now had the longer and fuller version of why there is no universal evolutionary drive toward complexity.

Now let me back up and take the long view.  And let me drill down to cells.  A chance confluence of circumstances caused the first living cell to come into existence.  Current scientific thinking says all life descended from a single cell.  But that is based on the fact that all modern cells share a lot of the same cellular machinery.  It's a good scientific theory because it is the simplest.  But that just means it can be tossed out the window and replaced by a different theory if evidence is found that discredits the current simple theory and supports a different more complex theory.

And science knows very little about this first cell.  But another assumption is that it was simple.  All the things that would have had to come together to make an extremely simple cell require an alignment of incredibly unlikely events.  But a lot of things happen when you take into account the entire earth and hundreds of millions of years.  That just means it requires a very large playing field (the whole earth) and a whole lot of patience (nearly a billion years) to create even a very simple cell.

But a more complex cell is, well, complex.  So it seems like this is asking too much to assume the first cells were complex at all.  If the necessary conditions for creating a complex cell happen once in a blue moon then it would be reasonable to believe that the circumstances necessary to create a very simple cell would happen on a daily basis.  It seems more likely, therefore, that more complex cells eventually emerged out of a large population of very simple cells.

Over time and space there would occasionally emerge the circumstances necessary to turn a relatively simple cell into a more complex one.  The more complex cell would evolve out of an environment containing many simpler cells much more quickly and easily than all on its own in a place where there were no simple cells available to jump start the process. This is a very reasonable argument but scientists just don't know enough to do anything but speculate as to whether it is correct or not.

And it is important to keep something in mind.  This whole fitness business is relative.  A very simple cell is probably not very fit compared to modern cells.  But what's its competition?  Nothing.  It doesn't have to be very "fit" because there is nothing out there trying to get it.  Sure, chance, or a change in circumstances (storm, volcanic eruption, etc.), could get it.  But that's just bad luck.  The concept of lunch, as in something seeing it as lunch, implies the kind of active competition for resources that was completely lacking back then.

Now let me return to my "more complex organisms can have a more complex response to their environment than less complex ones" argument.  If an organism is capable of a more complex response to its environment than another organism then the potential exists to do better.  Consider an organism that is only capable of a simple response to a predator, say wiggling.  Now consider a slightly more complex organism that can both wiggle and can chose the direction it wiggles in.  Both may or may not survive a given attack but it seems likely that the organism that can chose its direction can chose to wiggle away from its predator and that should give it a better chance at surviving.

But if neither organism is complex enough to be able to wiggle then it doesn't matter if there is a direction that would work better than others.  You can't do what you can't do.  Simple cells can't do much.  It is unlikely, for instance, that they can wiggle.  But wiggling has a cost.  It uses up energy that could be used for another purpose.  So complexity in the form of being able to wiggle has a cost.  The trick is to gain more in benefit than you lose in cost.  And that means just a random increase in complexity is often going to cost more than it benefits.  And that means adding complexity is not as straight forward as it initially seems.

But if you get it right it is helpful.  And we now don't see simple single celled creatures in our modern world.  The simplest single cell creatures we now see are actually very complex.  As such all modern cells are capable of displaying very complex responses to their environment.  And what that means is that if you introduced a very simple cell into our modern environment it would probably not take long for some modern cell to notice that cell and turn it into lunch.  And the simple cell would be incapable of mounting an effective defense.  So all the simplest cells are long gone from the modern environment.  And that means we have no place to look to see what they would have looked like and how they would have worked.

And you now have all the pieces of my theory.  I theorize that the interactions between cells in a multi-celled creature needs to be quite complicated in order for the new configuration to be beneficial (more fit).  For the reasons elucidated above the evolution of complex cells was a very slow process.  It may have depended on changes like removing most of the Sulfur, Iron, and Carbon Dioxide from the environment and adding Oxygen and other components, or not.  But I speculate that quite a bit of quite complex cellular machinery must be on hand to make a two-or-more cell organism more fit than one celled organisms.

How complex?  I am not an expert.  In fact, I try to avoid the "wet" sciences.  But I have picked up a lot of information along the way.  So let's take a tour of a modern cell.  We start with the outer membrane.  It's job is to keep the outside stuff outside and the inside stuff inside.  But this turns out to be a quite complex process.  Things need to move in the correct direction on a continuous basis.  But only the right things.  So the outer membrane contains things called "ion channels".  Ions are things like Potassium and Sodium.  The inside of the cell requires that the proper amounts of each be maintained.  So each channel must monitor external and internal conditions and cause the right amount of the right kind of ions to flow in the right direction.  And this is the simplest thing that's going on.

In general the outer membrane must pull raw materials in and push garbage out.  But wait, there's more.  There is the whole "signaling" process.  Take a simple example.  The outside of the outer membrane contains things called "receptors".  These receptors continuously sample the environment outside the cell looking for specific chemicals.  When the right chemical comes along it gets "bound" to the receptor.  When this happens something changes within the cell.  This is the process used by Morphine.  Certain brain cells have "Morphine" receptors.  This kicks off a change within the cell that results in pain signals from the rest of the body getting shut down.

There are many cells in our bodies.  Different cells have different suites of special purpose receptors.  Most cells are indifferent to most chemical signals.  But this business of some cells in the body manufacturing some chemical that travels to the site of a different cell then attaches to a receptor is a common method of intercellular communication.  It depends on specific cells being able to manufacture and release specific chemicals which can then travel around in the body and eventually find the correct receptor on the correct cell.

Scientists literally don't know who many of these unique communications paths there are.  Suffice it to say that the number is more than 10,000.  And these chemicals don't always come from a cell located elsewhere in the body.  As morphine (and caffeine and LSD and the AIDS virus and untold other examples) demonstrates, the chemical can come from pretty much anywhere.  That's enough about the outer membrane.  It is complicated but not by any stretch of the imagination the most complicated part of cells.

If there is an outer membrane it stands to reason that there is another membrane.  And the obvious (and correct) name for this is the inner membrane.  So what's inside it?  That's where the cell's DNA and associated machinery resides.  DNA has the form of a double helix.  For our purposes that means it has two backbones.  Is there a difference between the two?  No!  The machinery of the cell can't tell one from the other.  And one of the things DNA is responsible for is holding the recipe for proteins.

Cells need lots of proteins and they need very specific proteins.  DNA contains the recipe for making each and every one of them.  It requires a quite complex set of mechanisms to turn the DNA information into the appropriate protein.  There is a piece of chemical machinery that scans down the DNA backbone.  Which backbone?  It doesn't matter as both backbones are scanned.  Anyhow, at some point a sequence of DNA bases is located that says "the recipe for a protein starts here".  The DNA is scanned a little further to see if it is the recipe for the right protein.  If not then the backbone scan continues.

But if it is the correct protein the chemical machine creates the starting end of the protein.  Then it reads the sequence of amino acids that make up the protein off of the DNA (see http://sigma5.blogspot.com/2016/04/dna-101.html for more on this).  It then fishes a free floating fragment of the correct amino acid out of the soup floating around inside the cell and attaches it.  It then moves on attaching amino acid after amino acid.  Eventually it hits the "this is the end" signal on the DNA backbone, completes the protein and quits.  Many of the various chemical machines are a specialized version of RNA.  RNA is a cousin to DNA.  The biggest difference is that RNA has only backbone while DNA has two.

But this is only one of the tasks the various components of the nucleus are capable of.  Another key process is cell division.  New cells are created by having one cell divide into two.  Part of this process involves copying all the DNA in the nucleus to make a second identical copy.  This is a very complex process.  And these two processes do not exhaust the capabilities of the chemical machinery resident in the nucleus.  But they are all I am going to talk about.

And then there is the middle, the part between the outer membrane and the inner membrane.  This is where the work of the cell is done.  And there are thousands of different kinds of cells in many creatures.  So there is "kidney" machinery in kidney cells, "brain" machinery in brane cells, "skin" machinery in skin cells, and so on.  And remember all these cells contain exactly the same DNA.  And they are all the many times great grandchildren of the single cell we all grow out of.

Think back to the machinery in the nucleus.  As cells divide often one will take on one role and the other will take on a different role.  How does this come to be?  Well, cells have a large amount of very complex regulatory machinery.  Some of it takes its orders from parts of the DNA that don't code for proteins.  Some of it uses different mechanisms.  But it's all there in each cell along with the other stuff I have talked about.

I hope I have given you a flavor of just how complex the cells that make up modern plants and animals are.  And by some process or another a liver cell has to figure out it is a liver cell then behave like a liver cell.  A brain cell must figure out it is a brain cell and then behave accordingly.  And so on.  This specialization was not necessary when critters only had a single cell.  Roughly speaking all the cells of a specific type of critter were the same.  But differentiation, the process of splitting one cell into two cells, each of which behaves differently, but differently in a very specific way, that's a capability that is necessary for multi-cell animals to have.

That's a lot of complexity.  And complex cells with complex behavior requires cells with a lot of cellular machinery.  Given all this and given the fact that complexity is not always a good thing it is not surprising to me that it took three billion years for cells to acquire all the complexity necessary to produce multi-cell critters that were fitter than single cell critters.  It would be nice if scientists knew how all this came to be but they don't.  All they know is that the pieces were finally in place roughly 800,000 years ago.

From there it did not take long (tens to hundreds of thousands of years) for widely different types of extremely successful multi-cellular organisms to come into existence.  Since they were so successful they evolved into many and bizarre critters.  But it didn't take long before there were lots of multi-cellular creatures around.  And at that point the level of fitness necessary to thrive and survive went up a lot.  And that resulted in most of these early different kinds of multi-cellular creatures being wiped out.

But evolution continued and things like bones and shells were developed.  These enhancements were again wildly successful so many wildly different variants quickly appeared.  And that quickly caused the level of fitness necessary to survive and thrive to again increase.  And so may of those early designs were quickly wiped out leaving creatures that for the most part we would recognize today.

But the Cambrian explosion was not the end of it.  Evolution continues to this day.  Darwin took note of animal breeders.  Dogs in particular now come in a wide variety of shapes, sizes, dispositions, attributes, etc.  This is because of the forced evolution dogs are subjected to by people.  There are entire breeds of dogs that were not in existence a few hundred years ago.  Darwin laid all this out more than 150 years ago but people, for reasons that are beyond me, don't find it convincing so how about this?

Scientists can now demonstrate evolution in the test tube in the lab over time periods of a single human lifetime.  There are very short lived single celled creatures that are easy to culture in the lab.  Zillions of them fit in a standard "chem lab" flask where they happily live out their lives.  They are born, live, breed, and die within a day.  That means you can rack up a thousand generations in three years or ten thousand in thirty.

Scientists have started out with a colony consisting of a large number (remember, they are small) of genetically identical single celled creatures of this kind in a flask in a lab.  They have in some cases just let them do their thing for generation after generation to see what would happen.  In other cases they changed their diets, or the amount of light they were subjected to, or the acidity of the solution they were cultured in, or other environmental variables.  In every case they wanted to see what would happen after a few or a few hundred or a few thousand generations.

These creatures are so simple that they can be frozen then brought back to life years later without suffering any harm.  So scientists regularly split one colony into two, each in its own flask.  Or they split a colony into two and freeze one half.  This lets scientists do things like repeating the same experiment multiple times or doing a family of experiments where a single parameter is changed by various amounts.  Later the critters can be genetically sequenced to see what has happened.  This has allowed all the basic tenets of evolution to be proved out in detail and in controlled lab experiments that can be preproduced by others.

My ideas about what happened during that three billion year period are pure speculation.  But the basic tenets of evolution are not.

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