Python Programming for Biology: Bioinformatics and Beyond

Figure 12.2.  The conservation of residues in a protease enzyme’s active site. The

active-site residues are those that are involved in the chemistry of the enzyme’s reaction,

and because of this they tend to vary little during evolution, as long as the function of the

enzyme is preserved. Invariant sites in this alignment are marked with ‘*’. Such important

residues may be discovered by doing multiple alignments of evolutionarily divergent

sequences, e.g. from different species, to see which amino acid residues are most

conserved. If an active site is not preserved this may tell us something important about the

function of the protein.

Genetic trees

On  the  whole,  groups  of  biologically  important  sequences  are  similar  to  one  another

because they are generated from common ancestors during the process of evolution. Such

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sequences that can be linked by their ancestry are often loosely described as a family.  A

family of sequences will arise as sections of chromosomes are duplicated and as different

groups of organisms evolve into separate species. As sequences diverge from one another,

their functions will also diverge, i.e. for different roles and different situations. However,

as  long  as  there  is  sufficient  similarity  to  link  one  sequence  to  another  we  can  still  infer

that sequences belong to a family.

Going a step further we can say not only that sequences are related, but also how they

are related. This is to say in what order they diverged from, or on occasion merged with,

one  another  and  hence  build  a  family  tree  for  the  sequences.  For  example,  by  using  the

most  variable  features  in  the  non-coding  regions  of  DNA  we  can  build  trees  of  closely

related  human  families.  In  order  to  build  a  genetic  tree  from  a  group  of  sequences  the

basic  procedure  is  to  generate  sequence  alignments,  and  hence  similarity  scores,  for  all

pairs  of  sequences.  The  task  then  is  to  use  the  scores  to  arrange  the  sequences  into  the

most likely tree-like arrangement; for example, by considering which arrangement is most

frugal with regard to the implied residue changes. Building an accurate tree is often very

difficult, given that the number of possible ways of arranging a tree can be immense.