This web page was produced as an assignment for Gen677 at UW-Madison Spring 2013
Protein Homology
Homology is a term used to describe relationships between traits[1]. Homologous structures are structures that share a common evolutionary ancestry[1]. In the context of proteins, this means that proteins in different species shared a single common ancestral protein some time in the past. Identification of homologs is of critical importance as it can indicate functional equivalence of a protein in other species[1]. This identification is important to scientific research as it allows scientists to identify possible model organisms with functional homologs of a protein of interest[2]. Research done on a model organism containing a protein homolog can then be applied to other organisms. There are three main kinds of homologous relationships: orthology, paralogy and xenology[2]. Orthology is homology as a result of speciation and is the focus of the following analysis [2]. Paralogy is homology as the result of gene duplication within the species lineage and xenology is homology as the result of horizontal gene transfer[1].
Homologs of Human MYO5a
For the purposes of this analysis the human MYO5a protein homolog was used as it is the most complete sequenced homolog of the horse MYO5a protein. All protein homologs were found using Homologene. All sequences were then confirmed using Basic Local Alignment Search Tool (BLAST). These programs take a single protein sequence and compare it across many genomes looking for areas of sequence similarity. The following file contains a list of all MYO5a homologs and their corresponding protein sequences.
myo5a_protein_homologs.docx | |
File Size: | 166 kb |
File Type: | docx |
Homologous Protein Reference Numbers
|
|
MYO5a Homolog Alignments
|
|
Analysis and Discussion
The homolog alignments of MYO5a made using T-Coffee and Clustal Omega show that it is a very conserved protein found across several domains of life. The homologs most closely related to each other were found to be vertebrates. The BLAST analysis showed that all vertebrate homologs analyzed, with the exception of the zebrafish, shared greater then 90% identity. This corresponds well to the fact that MYO5a is very important in neurons and thus in vertebrates in particular where is it most highly consevered. The invertebrates analyzed had between 36% and 43% identity
The T-Coffee alignment found MYO5a to be least conserved in the mosquito, roundworm, yeast, fruit fly and Mustard plant. The alignment showed that there is a region towards the end of the protein, from approximately amino acid 1105 to 1728 in the consensus sequence, where sequence alignment is fairly weak while the rest of the alignment has average to good alignment across all species. The Clustal Omega alignment agreed with the T-Coffee alignment, showing high conservation among vertebrates. The only difference between the two alignments was the placement of yeast. The T-Coffee alignment has it associated very closely to arabidopsis and the Clustal Omega alignment have it more closely associated to the vertebrates.
The T-Coffee alignment found MYO5a to be least conserved in the mosquito, roundworm, yeast, fruit fly and Mustard plant. The alignment showed that there is a region towards the end of the protein, from approximately amino acid 1105 to 1728 in the consensus sequence, where sequence alignment is fairly weak while the rest of the alignment has average to good alignment across all species. The Clustal Omega alignment agreed with the T-Coffee alignment, showing high conservation among vertebrates. The only difference between the two alignments was the placement of yeast. The T-Coffee alignment has it associated very closely to arabidopsis and the Clustal Omega alignment have it more closely associated to the vertebrates.
References
[1] Mindell DP., Meyer A. (2001) Homology Evolving. Trends in Ecology and Evolution 16(8):434-40.
[2] Kuzniar A., Van Ham RCHJ., Pongor S., Leunissen JAM. (2008) The quest for orthologs: finding the corresponding genes across genomes. Trends Genet. 24(11):539-51.
[3] Dereeper A., Audic S., Claverie J.M., Blanc G. BLAST-EXPLORER helps you building datasets for phylogenetic analysis. BMC Evol Biol. 2010 Jan 12;10:8. (PubMed)
[4] 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 Research. 2008 Jul 1; 36 (Web Server Issue):W465-9. Epub 2008 Apr 19. (PubMed)
[5] Notredame C., Higgins DG., Heringa J. T-Coffee: A novel method for fast and accurate multiple sequence alignment. J Mol Biol. 2000, Sep 8;302(1):205-17. (PubMed)
[2] Kuzniar A., Van Ham RCHJ., Pongor S., Leunissen JAM. (2008) The quest for orthologs: finding the corresponding genes across genomes. Trends Genet. 24(11):539-51.
[3] Dereeper A., Audic S., Claverie J.M., Blanc G. BLAST-EXPLORER helps you building datasets for phylogenetic analysis. BMC Evol Biol. 2010 Jan 12;10:8. (PubMed)
[4] 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 Research. 2008 Jul 1; 36 (Web Server Issue):W465-9. Epub 2008 Apr 19. (PubMed)
[5] Notredame C., Higgins DG., Heringa J. T-Coffee: A novel method for fast and accurate multiple sequence alignment. J Mol Biol. 2000, Sep 8;302(1):205-17. (PubMed)