Editing Sequence motif (section)

====Phylogenetic motif discovery====
Motifs have also been discovered by taking a [[phylogenetic]] approach and studying similar genes in different species. For example, by aligning the amino acid sequences specified by the GCM (''glial cells missing'') gene in man, mouse and ''D. melanogaster'', Akiyama and others discovered a pattern which they called the [[GCM transcription factors|GCM motif]] in 1996.<ref name="Akiyama1996">{{cite journal | vauthors = Akiyama Y, Hosoya T, Poole AM, Hotta Y | title = The gcm-motif: a novel DNA-binding motif conserved in Drosophila and mammals | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 25 | pages = 14912–6 | date = December 1996 | pmid = 8962155 | pmc = 26236 | doi = 10.1073/pnas.93.25.14912 | bibcode = 1996PNAS...9314912A | doi-access = free }}</ref>  It spans about 150 amino acid residues, and begins as follows:

: <code>WDIND*.*P..*...D.F.*W***.**.IYS**...A.*H*S*WAMRNTNNHN</code>

Here each <code>.</code> signifies a single amino acid or a gap, and each <code>*</code> indicates one member of a closely related family of amino acids. The authors were able to show that the motif has DNA binding activity.

A similar approach is commonly used by modern [[protein domain]] databases such as [[Pfam]]: human curators would select a pool of sequences known to be related and use computer programs to align them and produce the motif profile (Pfam uses [[hidden Markov model|HMMs]], which can be used to identify other related proteins.<ref>{{cite web |title=Modelling in Pfam |url=https://www.ebi.ac.uk/training/online/courses/pfam-creating-protein-families/modelling-in-pfam/ |website=Pfam |access-date=14 December 2023 |language=en}}</ref> A phylogenic approach can also be used to enhance the ''de novo'' MEME algorithm, with PhyloGibbs being an example.<ref name="Siddharthan2005">{{cite journal | vauthors = Siddharthan R, Siggia ED, van Nimwegen E | title = PhyloGibbs: a Gibbs sampling motif finder that incorporates phylogeny | journal = PLOS Computational Biology | volume = 1 | issue = 7 | pages = e67 | date = December 2005 | pmid = 16477324 | pmc = 1309704 | doi = 10.1371/journal.pcbi.0010067 | bibcode = 2005PLSCB...1...67S | doi-access = free }}</ref>