SRD5A2: 5-alpha-reductase type 2 and Male Pattern Baldness 

This web page was produced as an assignment for Gen677 at UW-Madison Spring 2009.

Profile   Homology   Phylogeny    Motifs

Sequence Homology and alignments among organisms.

    Using Homologene, a number of homologous structures were found in many model organisms.    This seems logical since  the enzyme coded for by SRD5A2 is used in the production of male sex hormones, and most sexually reproducing species have marked differences between genders.  Interestingly, there was also a highly homologous structure found in Arabidopsis that has a conserved function.  A sequence profile for each of the species with homology, which includes a number of model organisms, can be found here.
    A very odd thing is that the chimpanzee was not listed as a homologous organisms by homologene, but when doing a BLAST alignment one gets 98% similarity and an E-value of 0.  Another very interesting fact is that the two isoforms are not actually very homologous.  In fact they share only around 50% sequence similarity, have different chromosome localization, enzyme kinetics, and even a different affinity for the main substrate testosterone (1). 

Alignments

T-COFFEE

tcoffeedna.pdf
File Size: 184 kb
File Type: pdf
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Muscle

muscle.docx
File Size: 36 kb
File Type: docx
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ClustalW

clustalw.docx
File Size: 15 kb
File Type: docx
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Analysis

The three big alignment programs all gave the same sequence results when used to compare SRD5A2.  I, did however prefer the output of T-COFFEE.  It was the most visually appealing and also the only one that allowed a .pdf output.  Each of the three programs were used from phlogeny.fr (2).  It may also be noted that DET-2 is not in any of the alignments.  I chose to leave it out, as it is the most different from the rest and skewed the results. 

References

1. Occhiato, E.G., Guarna, A., Danza, G., and Serio, M. (2004) Selective non-steroidal inhibitors of 5alpha-reductase type 1. The jouranl of Biochemistry and Molecular Biology. 88:1(1-16), doi10.1016/j.jsbmb.2003.10.004  

2.  Dereeper A.*, Guignon V.*, Blanc G., Audic S., Buffet S., Chevenet F., Dufayard J.F., Guindon S., Lefort V., Lescot M., Claverie J.M., Gascuel O. Phylogeny.fr: robust phylogenetic analysis for the non-specialist. Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W465-9. Epub 2008 Apr 19. (PubMed) *: joint first authors