Gene Cloning

240 Gene Cloning
Box 8.3 Phylogeny, Parsimony and Dendrograms
Mutations, which arise by chance, give rise to slightly different versions of genes and proteins.
While some of these mutations may affect the fitness of the organism most will be
neutral. Mutations which confer a selective advantage and mutations whose effect is neutral
will be inherited by subsequent generations. One of the ways in which we can study
evolutionary relationships is to compare the sequences of proteins or nucleic acid molecules
in living organisms, using the accumulation of mutations as a “molecular clock”
reflecting the evolutionary distance between the molecules, and hence the organisms
which carry them.
Imagine a short amino acid sequence such as (a). It would require three mutations, of one
amino acid at a time, to change it to sequence (c).
(a) M S A T H C (a) M S A T H C
I S A T H C I S A T H C
(b) I T A T H C (b) I T A T H C
(c) I T A G H C L T A A H C
(d) L T A A H C
This process is a bit like one of those word games where you have to get from the word
“fish” to the word “bike” in the fewest possible steps. (I can do it in five.) This analogy works
well because in the word game each intermediate has to be a real word. In the world of
amino acid sequences each intermediate needs to be a functioning protein. In this example
it is also possible to arrive at sequence (d) in four mutational steps, and in both pathways
there is a common sequence (b). There are of course many other pathways between
sequences (a) and (c), many just as plausible as the one shown. However, some involve
non-conservative substitutions and are likely to result in proteins which do not function,
these will not be part of the evolutionary pathway. Others involve more steps and so are less
parsimonious; evolutionary theory assumes that the shortest or most parsimonious route is
the most likely unless there is evidence to the contrary.
Branching diagrams or dendrograms are used to represent the evolutionary relationship
between sequences. Both of the dendrograms shown below are representations of the
relationship between the sequences used in this example. Sequences are linked by a line
with those to which they are most similar and the length of the line indicates the number
of intervening sequences. Diagram a) makes no assumptions about the direction of evolution
and is referred to as an unrooted tree. Diagram b) assumes that the sequence ISATHC
is the ancestral sequence and that the others have evolved from it; this is called a rooted
tree.
(a)
a
2 2
b
1
c
d
(b)
1 1
a b
1
c
2
d