Download Bio 120 Principles of Evolution Discussion Exercise 2 Optimality of

Bio 120 Principles of Evolution
Discussion Exercise 2
Optimality of the Genetic Code
Introduction
As indicated in the first lecture, the number of possible genetic codes in enormous. This
simple fact raises the question of whether the Universal genetic code reflects simple a random
choice among all those possibilities, or is in some way "optimized", i.e. whether the code and its
properties have been shaped in some way by natural selection. We know that the genetic code
can evolve because it is not truly universal. For example, in the mitochondria of vertebrates, the
codon AGR codes for the amino acid serine, rather than arginine as in the universal code. In
many protozoans UAR codes for glycine rather than the normal STOP. And in Mycoplasma,
UGA codes for tryptophan rather than serving as a stop codon. Moreover, it is quite possible that
code evolution was more common when the code was first being established. If such evolution
occurred, did it in some way optimize the code so that it functions better than a random code?
One suggestion that has been put forward is that the code has been optimized to mininize
the adverse effects of mutation on protein function. Redundancy of the code achieves this
optimization to some degree because synonymous base pair substitutions do not result in any
change in protein structure. However, there are many ways redundancy may be built into the
genetic code, and it is not intuitively obvious that the structure of redundancy in the universal
code is the best possible for minimizing the adverse effects of mutations.
Another way that the genetic code might minimize the adverse effects of mutation is by
maximizing the probability that a non-synonymous mutation (a mutation that causes an aminoacid substitution) will substitute an amino acid with properties similar to the original amino acid.
Substitution of an amino acid of similar charge, polarity, size, etc., will cause minimal disruption
of the three-dimensional structure, and hence function, of the resulting protein. While it seems
intuitively plausible that different genetic codes may do better or worse at optimizing this property
of the code, it is not at all clear how well the actual code does in this regard.
Exercise
In this exercise you will work as a group to design a computer program to determine
whether the genetic code is optimized. In particular, you will design a program that determines
how well the actual genetic code minimizes the adverse effects of mutation compared to a random
set of alternative codes. The program and your associated analysis should have several elements:
1. A method for evaluating how well any given code minimizes the effects of mutation.
For this you will need to pick some criterion that measures the adverse effects of amino-acid
substitution (i.e. change in polarity, charge, size, etc. or some combination of these). The
program will have to calculate an average change in the criterion for possible to consider all
possible mutations that could occur in the genetic code.
2. A method for generating alternate genetic codes.
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Bio 120 Principles of Evolution
Discussion Exercise 2
Optimality of the Genetic Code
3. A statistical method for evaluating whether the actual genetic code performs better
than the average random code you generate.
As in the previous exercise, many (possibly most) of you will not be equipped to write an
actual computer program. For those who can, you are encouraged to do so. For those who can't,
you will be expected to hand in a detailed flow-chart describing very precisely what that program
would do. Your flow chart should be detailed enough to allow a skilled programmer who has
little knowledge of evolutionary biology to write the program. Further details will be given by
your Teaching Assistant.
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