Biology Reference
In-Depth Information
5
Summary
Multiple Sequence Alignment requires homologous sequences; the
BLAST and FASTA programs calculate both alignment scores
and accurate estimates of their statistical significance that can
be reliably used to infer homology. Protein alignment scores with
E
()
<
0.001 in a single search reliably reflect homology—sequences
that have descended from a common ancestor. Searches for homologs
are far more sensitive at the protein level. Protein sequences change
more slowly than DNA sequences, providing greater evolutionary
look back time; protein alignments have more accurate statistical
estimates; and protein databases are dramatically smaller than DNA
databases. Today, most sequences are determined as DNA, but
blastx
and
fastx
can automatically translate those sequences and
compare them to protein databases. Search sensitivity can be increased
by searching smaller, representative databases, and using scoringmatri-
ces that are targeted to the length and evolutionary distance of the
sequences of interest. Because protein sequence databases have
become so diverse, it is rare that a query sequence does not find
homologs; the most common reason for failing to find homologs is a
query sequence that is largely low-complexity or strongly biased
amino-acid composition. It is routine to find homologs between
human and bacterial proteins that last shared a common ancestor
more than 2.5 billion years ago. Sequence comparison has improved
dramatically since it became generally availablemore than 25 years ago;
sequence databases are far more comprehensive, and statistical esti-
mates are far more reliable. It has become much easier to identify
homologs, which can provide more data for Multiple Sequence
Alignments.
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