

"Perhaps one of the most important [recent] papers .. in evolutionary biology"  - Herring
http://sciencenow.sciencemag.org/cgi/content/full/2009/923/1

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ramanujan
This is a good paper with an empirical example of a _molecule level_ ratchet
effect, but the message here is way overstated. It is definitely NOT the case
that evolution "can't go in reverse" as a categorical statement.

1) First and most importantly, if selection pressure was reversed in sexually
reproducing species, it is (a) unlikely that the ancestral allele will ever
_completely_ die out and (b) also unlikely that a sequence of recombinational
events could not reconstruct the ancestral allele.

So reversed selection pressure would lead to an increase in frequency of the
ancestral allele. Doesn't require the (much higher) level of difficulty of
pushing six consecutive mutations to fixation in a single protein.

In bacteria or archaea it would be even easier -- just pick up the ancestral
allele through horizontal gene transfer.

2) Second, even discounting sexual reproduction for now, given strong enough
reversed selection pressure, either the species would go extinct or (more
likely) some other protein would have been co-opted into pursuing the new
function. That is, this road might be blocked but another one will almost
certainly be open.

3) Third, this _particular_ example has an accumulation of several mutations
that act as blockades in fitness space. But this is far from generally proven.
You'd need to do some serious correlation of activity with multiple
sequence/structure alignments across large families of proteins to show this
ratchet effect.

4) Finally, the whole concept of QSAR (quantitative structure activity
relationships) is based on the idea that activity-structure relationships
_tend_ to be more continuous than not, in the sense that small changes
_usually_ have small effects on activity [though in dealing with adding atoms
to molecules, you're talking about irreducibly large step sizes in different
dimensions]).

And continuous alterations in activity usually imply reversibility as a
function of many small steps.

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xel02
Summary: The reversibility/irreversibility of evolution has been difficult to
measure empirically. The researchers found a protein and its ancestral
protein. They found key mutations that act like evolutionary ratchets. If the
key mutations are left in place and the protein reversed to its ancestral form
it became non-functioning (and would probably be a harmful mutation).
Furthermore changes in the key mutation did not lead to any advantages in the
ancestral protein. This means that there is a mechanism where a protein can
mutate but is unlikely to mutate back, and this is a specific example of how
evolution can be irreversible.

~~~
btilly
Exactly, it is a version of "use it or lose it". Think of cave-dwelling fish
who no longer use their eyes. They lose the capacity for sight. And once lost,
it isn't coming back.

To give more detail, they were looking at an important protein which appears
in many species. Since they know the protein for many modern species, and they
know when different species branched off, they can reconstruct the likely form
of the protein at each branching. Given modern computer modeling, they can
figure out what each version of the protein will do. They demonstrated that it
used to respond to 2 hormones. 40 million years later it responded to only 1
of those. They identified the responsible mutation and found that random
mutations that happened after the first would cause it to respond to nothing
if you undid the mutation.

In short, a significant mutation opens the door for further mutations that
make the first irreversible.

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yannis
If not the most important certainly worth a read. Here is a link to the actual
paper.

[http://www.uoregon.edu/~joet/PDF/bridgham-thornton-
nature200...](http://www.uoregon.edu/~joet/PDF/bridgham-thornton-
nature2009.pdf) [pdf]

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aboodman
I am missing why this is important or unexpected.

Since most mutations are no-ops, and behavior is frequently expressed through
combinations, I'd have expected what they found. For every useful mutation,
there were usually other random mutations that prevent simply flipping back
the useful one.

~~~
btilly
Science isn't about collecting reasonable sounding ideas. It is about
collecting useful ways of understanding the world that have been stress-tested
until we can have great confidence in them.

The paper is the first time anyone has been able to provide solid evidence
about whether the evolutionary mechanism you outline really happens. It's the
difference between a note in Fermat's margin saying that he has a proof but
the margin is too small, and Andrew Wiles writing up a several hundred page
proof. Now that it has been demonstrated how to show which mutations are
irreversible, the door has been opened to using molecular genetics to provide
absolutely definitive answers to questions about the evolutionary tree that we
don't have good fossil evidence for.

Furthermore the ability to test specific questions about the functionality of
putative reconstructions of particular prehistoric genes does a _lot_ to
improve our confidence that we're reconstructing them correctly. We've now
been able to compare versions of a gene from 440 million years ago and 400
million years ago and gotten specific enough answers back that suggest we've
got both versions of the gene right. Monkeys and apes split perhaps 30 million
years ago. How accurately can we figure out the genetics of that last common
ancestor?

