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"He who sees things from their beginnings will have the most advantageous
view of them." ------Aristotle
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Ontogeny and Phylogeny III:
Developmental Biology of Phage Lambda
In previous postings we dealt with the abstraction of the ontogenic
development into the ontogenic chain, the cost of lengthening the ontogenic
chain, the importance of constructing vital organs and tissues at early
developmental stages, and teh likelihood of the vertebrate head having
evolved as a consequence of an ontogenic side chain. I ended the last
posting by asking if there is any positive evidence that the evolution of
the vertebrate head can be attributed to an ontogenic chain.
This question on the evolution of the vertebrate head was originally
intended to be answered in this posting. However, on a second thought I
decided to slow down the pace. The vertebrate head is a complicated
structure whose embryonic development requires the interaction among
ectomesenchyme (the neural crest cells), the paraxial mesoderm, the lateral
mesoderm and the ectoderm. Because most of you (most of my readers) have an
engineering background, you may very soon be overwhelmed by developmental
terminology and may not be able to comprehend what I will be talking about
the evolution of the head. If I sell the head to you now, you may not even
recognize it because it will not be the vertebrate head you have seen.
Now my strategy is to give you a raincheck for the vertebrate head and sell
you something else. Don't think that this something else is trivial. What
we will explore is a creature that should have been the dream of an
evolutionary developmental biologist come true.
The creature is small but beautiful, and it has a name that is almost
mathematical: bacteriophage lambda, or simply, phage lambda.
Phage lambda is a parasite of the bacterium, Escherichia coli, which
inhabits our guts as well as all molecular biology laboratories. Once inside
a bacterial cell, phage lambda has two developmental pathways: lytic pathway
and lysogenic pathway. In the lytic pathway, the phage replicates, lyses its
host and initiates another wave of invasion into other bacterial cells. In
the lysogenic pathway, the phage incorporates itself into the bacterial
genome and passively replicates itself through replication of its host.
As evolutionary biologists, we expect the phage to employ whatever
developmental strategy to maximize its survival in the next generation. Now
that these two developmental strategies (lytic and lysogenic) differ so much
from each other, it is almost certain that they will not be equally good in
all different circumstances. Most likely they will be employed at different
circumstances.
It turns out that the phage does make decisions. Once it is inside the
bacterium, it checks, directly, whether the medium is rich (i.e., whether
the bacterial colony is rapidly replicating). If the bacteria/phage ratio
is large (i.e., there are many hosts available), the lytic developmental
pathway is chosen. The phage rapidly replicates, lyses the host, and invade
other hosts. On the other hand, if the bacteria/phage ratio is small, the
lysogenic pathway is taken. The phage squeezes itself into the cozy home of
the host genome and awaits for future opportunities of replication. In this
state the phage is called a prophage.
But a bacterium, being vulnerable itself, is by no means a safe heaven for
the prophage. There are many factors that can damage bacterial DNA and
destroy the cozy home of the prophage. For this reason, the prophage has to
collect and analyse information of its host, and make decisions based on the
analysis. Almost as soon as you expose the host bacteria to physical or
chemical factors that damages the bacterial DNA, the prophage will rapidly
decide to desert its host. It will suspend the expression of genes that
maintain the lysogenic phase, cut itself out of its host genome, initiate
the lytic developmental pathway, replicates and lyses its already fatally
injured host. The phage is truly the most ungrateful creature our Mighty God
has ever created! Or is it Satan's masterpiece? Its mathematical name now
only reminds us of the evil Moriaty (spelling?) in Sherlock Holmes.
Fortunate for future developmental biologists who will model the
evolutionary dynamics of phage development, the genetics of the creature has
been worked out in great detail (see Lambda II by Hendrix et al. 1983 and
The Genetic Switch, 2nd edition by Ptashne 1992). What lays in front of us
is no longer an abstract ontogenic chain, but a well debugged genetic
program written with innovation, originality, charm and elegance. When I was
a visiting scientist at the Department of Genetics of University of
Washington, I used to sit in the departmental library and stare at its
genetic map for hours, forgetting all what I was supposed to do. I suggest
that you locate its genetic map in Maniatis' Cloning manual and stare at it
for a while. You would really appreciate the power of natural selection.
But it will be a kind of natural selection few evolutionary biologists have
appreciated.
Xuhua Xia
University of Manitoba
(to be continued)
