DNA Clocks

What shape is a calendar?  How long is a clock?

I know these questions look like those nonsense computer generated sentences created by randomly assembling nouns and verbs, but they are not.  They are honest-to-goodness questions with honest-to-goodness answers.

The answer to the first question, it’s a double helix, gives us a clue to what is going on.  For all of us, “double helix” automatically says DNA.  All our genetic information, our DNA, is stored in chromosomes, 22 of them, plus the X & Y.  These different chunks of DNA are part of the tricks nature uses to cram a bloody huge molecule into a tiny package.

How big?  If you took a human DNA molecule and stretched it out into a single, ladder-shaped chain, how long would it be?

Answer: Over 2 meters long!  Imagine!

To make a new cell, that huge molecule, containing about 30,000 genes, has to be copied…exactly.  The reproduction process requires splitting the humongous ladder lengthwise and then using each half to reproduce its missing side.

Not too surprisingly, that copying process is prone to the occasional error.  Therefore each cell has “proof checking” mechanisms to find and correct them.  Still, the truth is that the occasional error in the occasional cell just doesn’t matter very much.  Cells are mostly kind of throwaways, anyway, being periodically replaced by new generations.

Except, that is, when we are talking about gametes, the reproductive cells.  An error in the creation of a gamete has the potential to be used in the creation of a new individual, with the error passed on to every cell of the new person and, far more importantly, into every descendent of that person.

For gametes, nature has given us even more mechanisms to make sure defective gametes aren’t fertile, and if they are, do not join with their sexual opposite number, and if they do, never come to term. (A set of protections, by the way, largely circumvented by in vitro fertilization.)

It is a great system, but not perfect.  Every once in a while, despite all the precautions, the rare error creeps in.  But the rate is pretty consistent.  Out of the roughly 9 billion ladder steps that make up your genome, about thirty of them don’t match either of your parents.

The result?  A clock.  Or a calendar, if you prefer.

If you went to a scientist and asked him to build you a clock, the first question he would ask is, “What time base?”  Give me a regular rhythm, whether it is the swing of a pendulum or the 60 Hz of the power company or the natural vibration of argon gas, and I will make you a clock.

That natural mutation rate, roughly thirty every generation, gives us the sine qua non of a clock.  A slow clock, maybe, but a clock just the same.  Each of us, all unknowing, is a kind of walking clock.

To measure what, you ask?

Why, our own species, of course.

Imagine, for a second, that I have a gamete mutation.  If I have offspring, each of them will share that mutation.  If they have children, so will the children.  And so on through the generations, my mutation will spread out, with ever greater numbers possessing it.  Some future scientist, detecting these mutations in some percentage of the population, could say that everyone in that percentage is related, whether they know it or not.  And by comparing the DNA of those people and knowing that they would have acquired thirty additional mutations for each generation, they can do a regression analysis, stripping away the differences contributed by each generation.  Eventually they could tell how many generations ago I lived and made my mutant contribution to the gene pool.

There is, however, a catch.  Sexual reproduction means that we get half of our genome from our mother and the other from our father.  That means that my mutation does not march down the generations in a nice, clear, isolated sequence.  Instead, each generation fuzzes up the signal by mixing in contributions from other folks.  In time, these genetic recombinations will so thoroughly obscure the signal that the useful information will be lost in the clutter.

Since this is a sex-based problem, it is nice to report that there are two solutions, a female and a male.

It turns out that there is another component to the human cell, the mitochondria, with its own DNA.  We get our mitochondrial DNA strictly from our mothers, which eliminates all those added signals.  Then, too, mitochondrial DNA is much simpler than our genomic DNA, which makes its analysis easier.  Nearly twenty years ago a team of scientists analyzed mitochondrial DNA, asking themselves questions: Looking backward, does the data converge (i.e., point to ancestral sources)?  How many convergence centers could be identified (i.e., how many ancestors)?  How many generations does it take for the data to converge?

The answers rather stunned the scientific world.  The data pointed to a single point of convergence and it was located about 200,000 years ago.  Our race seemed to have had a single ancestral mother (they called her Eve), who lived in a time before the race of humans had migrated from their home continent:  Eve was African.

The second sexual solution, the male one, came quite a bit later.  The trick here is that our gender is determined by whether we got an XX chromosome pair or an XY.  If you’ve got an XY, then you are a male…and you got that Y from your father.  Once again, no genetic recombination confusion.  No nasty mixing of the mutation signals.

As they say, there is both good news and bad news.

The bad news is that the Y chromosome is much bigger.  Instead of analyzing 16,000 nucleotide units (as in mitochondrial DNA), we are having to deal with the colossal 50 million nucleotides of the Y chromosome.  This means that both the chemistry and the math are lots messier.

On the other hand, the good news is that with so much information to analyze, the potential resolution of the analysis is lots better.  So much better that we can actually construct a phylogenetic tree of the whole human race, repeatedly tracing mutations backwards from all the possessors of a given mutation to The Most Recent Common Ancestor (TMRCA).  Each TMRCA represents a branching point on our human lineage.  Eventually, we are led back to our first branching point, the one shared by everyone who migrated out of Africa.  We finally arrive back at our first common male ancestor (whom they have dubbed Adam).

This tree has allowed us to map, in terms of geography versus time, the routes of humanity’s migrations.  If one group veers left and another right, they will share all the mutations before the split and only their own after it.

For example, we can see that a group of our ancestors (possessing the M89 mutation), left Africa around 45,000 years ago, then split into two groups.  The smaller moved directly into Europe, acquiring M172 on the way.  The bigger veered right and settled on the steppes, where they acquired M9.  They moved north (M45), then west (M173), finally reaching Europe, where their great numbers almost swamped the survivors (the M172’s) of the first settlers.  It’s all there to be read in the genes.

This technique is one of the most powerful and elegant scientific tools I’ve ever seen.  Still, it is a human tool, and all such seem to come with a mandatory dose of irony and unanswered questions.

In this case, we know that mitochondrial Eve lived in Africa about 200,000 years ago and is our common ancestor.  The corresponding male ancestor, Y chromosome Adam, lived in Africa, too,  only something around 60,000 years ago.

Adam and Eve, it seems, never met.

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