Saturday, February 9, 2013

Toy DNA Analysis Part III: Eve of Reconstruction

After the first and second activities of the morning, there was not
much more than 30 minutes left.  I wanted to do an activity with
mitochondrial DNA, so I went over the background first. (They had seen
much of the following earlier in the year, but the review turned out
to be necessary.)

Each cell has a nucleus which contains DNA, surrounded by the bulk of
the cell ("cytoplasm") which has various structures ("organelles") for
performing various functions.  One type of organelle is mitochondria,
when help you turn oxygen into energy.  Each cell has many
mitochondria, and here is the amazing thing: they have their own DNA!
They are not built according to instructions recorded in the DNA of
the nucleus; they simply reproduce by dividing asexually, as if they
were self-contained cells within the cell.  When the cell itself
divides, each daughter gets half the cytoplasm and therefore half the
mitochondria.  It is thought that mitochondria were once independent
bacteria, which learned to cooperate so well with other cells that
they took up residence.  That's pretty amazing!  Another amazing fact
is that all creatures on Earth share the same DNA code.  We are all
related, even humans and yeast.  (Example: if you put the DNA letters
for human insulin in yeast, the yeast understand those instructions
perfectly and makes human insulin.)

When a human egg cell is fertilized, the sperm carries in half the
nuclear DNA to complement the mother's half of the nuclear DNA.  But
the egg has an enormous amount of ctyoplasm and the sperm contributes
none.  So your mitochondrial DNA is an exact replica of your mother's,
and of her mother's, and of HER mother's....there is no shuffling with
each generation as we have with nuclear DNA.  Thus, mitochondrial DNA
makes it much easier to test whether you are a direct descendant
(through an all-female line) of, say, Cleopatra.  (A similar thing can
be done with Y chromosomes and all-male lines of inheritance.)
Furthermore, by mapping the geographical distributions of
mitochondrial DNA, we can trace out migrations of women over time.
(Ditto for Y chromosomes and men.)

It's good to ask the kids a few questions to see how well they
understand.  In this case, a girl said she was sorry for boys because
they had no mitochondria.  So we discussed that issue again: everyone
has mitochondria (that's how they turn oxygen into energy) but boys
won't pass theirs on to their kids.  Moms really do contribute more
than half, as immortalized by this song.

But there can be mutations. It turns out they're fairly rare in
mitochondria, probably because most mutations would be fatal very
early on.  But they do happen.  So if we gather mitochondrial DNA from
a large sample of people, we will find sequences that differ by a
little bit.  We should be able to trace the mutations backward and
reconstruct ancestor DNA.  For example, if we saw sequences GATTACA,
GATTACT, and AATTACA, we might guess that the ur-grandmother, many
generations back, of all three people had the sequence GATTACA.  One
mutation somewhere along the line would explain the people with
GATTACT, a different mutation somewhere else along the line would
explain the people with AATTACA, and the people who had never
experienced a mutation along their line would still have GATTACA.
They hypothesis of, say GATTACT being the ancestor is much less likely
because it requires that there was one mutation to make it GATTACA and
then, in the line with this mutation already present, there was
a second mutation making AATTACA.

So here's the problem I posed to the kids: reconstruct the ancestor of
these sequences:

CATTACGACT     
GAATACGACA      
GATTACAACT      
GATTACGACA      
GATTACGACT      
GATTATAACT
GATTCCAACT      
GTTTCCAACT      

Go ahead: print these out and cut them into strips, try to arrange
them as leaves of a tree, and guess what the branches and trunk have
to look like.

Some groups were lost, and so I tried to work it out with them on the
board, starting by making a guess about the immediate ancestor of one
very similar pair.  It turned out this was probably a bad guess,
because once we had worked out two hypothetical ancestors of two
different pairs, those two hypothetical ancestors seemed to have very
little in common, whereas we would have expected them to look similar
enough that we could guess a hypothetical original ancestor which
spawned them both.  Just as I was realizing that we were almost out of
time, another group handed me a sheet of paper in which they had
worked it all out.  The lesson I drew for everyone: don't be afraid to
take a guess, work out the consquences of that guess, and if it
doesn't work, scrap that guess and start over.  That's what science is
all about! (See the first minute or so of this video.)  Just because
lunchtime was coming up fast does not mean that we had done anything
wrong.  The wrong thing would be to continue pushing a guess which
doesn't explain all the evidence.

If I do this activity again, I would print out very large copies of
the sequence so I could rearrange them easily on the board (writing
with chalk does not lend itself to rearrangement).  Or I would print
it at regular size and use a document camera.  I would probably also
walk them through a simplified example first as I did in writing this
post.  Another idea I just had is to try representing the information
differently.  Perhaps a color code instead of letters would make
things just jump out. 

I saved a few minutes for the coolest part of this: because we know
that mutations happen about once every 10,000 years, we can use this
as a clock.  In my simplified example, you have to reverse-engineer
three mutations to get back to a common ancestor which explains all
the data.  That makes 30,000 years.  In real life with real data, you
have to go back 200,000 years, but you can do it.  That means that
there was one female about 200,000 years ago from whom every human
alive today has inherited their mitochondrial DNA; she is called
mitochondrial Eve.  This doesn't mean that other females living at
that time didn't contribute to people alive today; they surely did,
through their nuclear DNA.  But mitochondrial Eve is the only one who
has an unbroken female line to anyone alive today.  And a similar
argument identifies "Y-chromosomal Adam" who lived around 100,000
years ago.  We are all intimately related!







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