Python Programming for Biology: Bioinformatics and Beyond

Figure 14.1.  An overview of the basic types of small-scale genetic change. Changes

in DNA sequence often arise through somewhat random processes, like errors in

replication or recombination, but in general variation is accepted non-randomly by natural

selection. The simplest change, shown as an alignment mismatch, is the substitution of

one type of nucleotide for another, called a single-nucleotide polymorphism (SNP), and

there may be many substitutions in a given length of DNA. Insertions and deletions are

apparent where a section of a sequence does not have an equivalent alignment match in

another sequence. Knowing the ancestor sequence will reveal whether the change was

actually an insertion or a deletion, though in general such changes are called ‘indels’

without disclosing the mechanism. Insertions and deletions are more likely to occur where

the DNA sequence is repetitive, which in turn results in variation in the numbers of a

repeated sub-sequence.

The other general way of DNA changing is via the action of viruses and transposons,

which  can  both  be  thought  of  as  mobile  genetic  regions.  Some  viruses  hide  their  own

genome  inside  that  of  their  host,  using  enzymes  they  bring  along,  thus  evading  host

defences  to  become  virulent  at  a  later  time.  Some  of  these  are  retroviruses,

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which have

RNA viral genomes, but make a DNA copy using a reverse transcriptase enzyme, i.e. the

reverse of the normal DNA to RNA transcription. Virus DNA that is inserted into its host’s

genome naturally causes a change in the DNA sequence, but it may not stay there. Often

viral DNA is cut out or excised from its host, sometimes leaving parts of its DNA behind.

For virus DNA that remains, it can sometimes change so that the viral sequence remains in

an inactive form, but is carried from that time onwards as its host reproduces. Transposons

are like viruses in that they can be considered as genetic elements that can move and they

often have similar means of inserting and excising their genetic material. However, unlike

viruses, transposons lack the means to escape a cell: coat proteins, infection receptors and

the  like.  They  are  sometimes  colloquially  called  ‘jumping  genes’.  Transposons  and  their

remnants are responsible for large proportions of many genomes, forming repetitive, non-

functional sequences (at least in the cellular sense; they arguably have a role in evolution).

Whatever the cause of a change in DNA sequence, its persistence relies upon it being

accepted.  If  a  change  is  detrimental  and  kills  a  cell  or  organism  or  carries  a  distinct

disadvantage,  then  that  change  will  tend  not  to  be  passed  on  to  future  generations.  If  a

change is neutral or carries an advantage, then it will tend to be accepted. Thus, although

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the causes of sequence variation are highly random, their acceptance by evolution is not at

all random. Indeed, when we observe variation in biological sequences most interest is in

determining what the consequences are for the biology, for individuals and species, rather

than the causal mechanics.