BLAST

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Chapter 2: Biological Sequences

genetic element or selfish DNA (a phrase coined by Francis Crick). These entities are

a bit like the fleas and ticks of the genome: they copy and spread themselves within

and between genomes and are generally believed to do little for the host genome.

Selfish DNAs are usually further classified into three subcategories: transposons, ret-

roviruses, and retrotransposons. If you see these names in a BLAST report, you may

need to use a repeat filter.

Pseudogenes

One of the most confounding problems in similarity searches is the presence of

pseudogenes. As the name suggests, pseudogenes are “fake genes”; that is, they look

like they could encode a protein, but they aren’t functional. Pseudogenes come from

a variety of sources. A mutation that introduces a stop codon into a gene creates a

pseudogene, but more commonly, pseudogenes are created from some kind of dupli-

cation event. Sometimes, through various mechanisms, regions of a chromosome

may become duplicated. The extra copies of genes are generally free of selective pres-

sures and may become pseudogenes as they accumulate mutations. Duplication may

also result from repetitive elements that include neighboring DNA as they copy

themselves into new locations. In eukaryotes, a very common form of pseudogene is

the retro-pseudogene, in which the mRNA from a gene is reverse-transcribed into

DNA and inserted back into the genome. Because retro-pseudogenes come from

mRNA, they contain the hallmarks of transcripts, notably an absence of introns and

the presence of a poly-A tail. They are therefore easy to detect if you know what to

look for. Most retro-pseudogenes come from highly transcribed genes such as the

protein components of the ribosome.

Biological Sequences and Similarity

The beginning of this chapter asked why biological sequences are similar to one

another. Let’s answer that question now. You’ve seen that biological sequences like

proteins may have important functions necessary for the survival of an organism.

You’ve also seen that DNA sequence can mutate randomly, and this may change

how a sequence functions. Over time, both functional constraints and random pro-

cesses impact the course of sequence evolution. The degree to which a sequence fol-

lows a functional or random path depends on natural selection and neutral

evolution. So the reason why sequences are similar to one another is because they

start out similar to one another and follow different paths. When you read a BLAST

report, you will find that your knowledge of molecular and evolutionary biology will

help you interpret the similarities and differences you see.