This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison
The Study of homology
First coined by Richard Owen in 1848, homology is defined as two sequences that share a common ancestor and is fundamental to Charles Darwin's Origin of Species. [1] Since, evolutionary theory predicts that related organisms derived from a common ancestor will share similarities, homology can be used to infer evolutionary relationships. Similarly, evolutionary relationships can be used to understand homology. [2] Protein homologues are also useful in identifying potential model organisms that would allow genetic manipulation and observation not possible in humans as well as indicating the importance and possible function of a protein that has not changed for thousands of years despite other changes throughout the genome. Care must be taken to not confuse analogous organisms with homologous organisms, however. While homologues share a common ancestor and diverge, analogs have separate evolutionary origins but appear superficially similar due to convergent evolution and natural selection. [3]
A decision on homology between proteins has to be made on the basis of the similarity between them and correlated to the probability that this similarity is not simply due to chance. The higher the similarity between two sequences of amino acids, the lower the probability that they have originated independently of each other and became similar merely by chance. Even for proteins that share a much lesser degree of identical amino acids, alignment of similar amino acids is often straightforward, and there seems to be no reasonable doubt of homology. [4]
A decision on homology between proteins has to be made on the basis of the similarity between them and correlated to the probability that this similarity is not simply due to chance. The higher the similarity between two sequences of amino acids, the lower the probability that they have originated independently of each other and became similar merely by chance. Even for proteins that share a much lesser degree of identical amino acids, alignment of similar amino acids is often straightforward, and there seems to be no reasonable doubt of homology. [4]
The homologues of the Tub protein
TUB protein homologues were initially identified using NCBI's Basic Local Alignment Search Tool (BLAST). BLAST identifies regions of local similarity between sequences by comparing amino acid sequences to sequence databases and calculating the statistical significance of the matches. After inputting the TUB protein sequence, BLAST provided a list of potentially homologous proteins in other species. These potential homologues were confirmed through reciprocal BLASTs (using the potential homologue's amino acid sequence as the input sequence to ensure that the human TUB was still identified as a homologue) and sequence alignments to visualize the similarity. The percent of amino acids that were identical to the human TUB and similar (a different amino acid that is similar in function) are shown in Figure 1 below. Homologene was also used to confirm the homologues initially identified through BLAST. While not all of the identified homologues listed below were found on Homologene, their successful reciprocal BLAST and alignment with the human TUB protein warrant their inclusion as a likely homologue. It is also important to note that the homologues shown below are not an exhaustive list of all potential TUB homologues. Instead, the image below displays the great variety of organisms, ranging from plants to humans, that contain TUB protein homologues.
Analysis of tub protein homologues
As can be seen in Figure 1, TUB is very well conserved in organisms ranging from plants to flatworms to frogs to chimpanzees, but there were no potential homologues identified in single-cellular organisms, such as yeast. Since all of the organisms shown above were verified to be homologues (and not analogs) through reciprocal BLASTs, it appears that the TUB protein may serve some essential function for all multicellular organisms. This assumption is supported by the fact that the TUB-1, the homologue of TUB, has been found to regulate fat storage in C. elegans. [5] As can be seen in the Clustal Omega alignment in Figure 2, the tubby domain at the C-terminus is nearly identical in all mammals and very well conserved even in plants pointing to its potential importance.
Homologue reference pages and numbers
Human (Homo sapien)-TUB, isoform a
Accession Number: NP_003311.2 GI Number: 19923167 FASTA Chimpanzee (Pan troglodytes)-TUB Accession Number: XP_003312952.1 GI Number: 332835808 FASTA E value: 0.0 Max identical: 99% Max Similar: 99% Mouse (Mus musculus) - TUB Accession Number: NP_068685.1 GI Number: 11230782 FASTA E value: 0.0 Max identical:95% Max Similar: 97% Dog (canis lupus familiaris)-TUB Accession Number:XP_542495.3 GI Number: 359322422 FASTA E value: 0.0 Max identical: 95% Max Similar: 97% Chicken (Gallus gallus)-TUB Accession number: XP_420992.3 GI Number: 513186354 FASTA E value: 0.0 Max Identical: 78% Max Similar: 86% Zebrafish (danio rerio)-TUB Accession number: XP_697114.2 GI Number: 125820946 FASTA E value: 0 Max identical: 76% Max Similar: 84% Drosophila (Drosophila melanogaster)-king tubby Accession Number: NP_995911.1 GI Number 45552773 FASTA E value: 2e-1214 Max identical: 63% Max Similar 80% Arabidopsis thaliana-tubby-like F-box protein 3 Accession Number: NP_850481.1 GI Number: 30690823 FASTA E value: 2e-56 Max Identical: 37% Max Similar: 55% |
Gorilla (Gorilla gorilla)-TUB
Accession Number: XP_004050695.1 GI Number: 426367349 FASTA E value: 0.0 Max Identical: 99% Max Similar: 100% Rabbit (Oryctolagus cuniculus)-TUB Accession Number: XP_002708837.1 GI Number: 291384590 FASTA E value:0 Max identical: 98% Max Similar: 98% Rat (Rattus norvegicus)-TUB Accession Number: NP_037209.1 GI Number 6981686 FASTA E value 0.0 Max identical: 96% Max Similar: 97% Dolphin (Tursiops truncates)-TUB Accession Number: XP_004328722.1 GI Number: 470650710 FASTA E value: 0.0 Max identical: 93% Max Similar: 96% Xenopus (Xenopus tropicalis)-TUB Accession Number: NP_001086168.1 GI Number: 147906681 FASTA E value: 0.0 Max identical: 76% Max Similar: 85% Fugu (Takifugu rubripes)-TUB Accession Number: XP_003970049.1 GI Number: 410913145 FASTA E value: 0.0 Max identical: 75% Max Similar: 84% C. elegans (caenorhabditis elegans)-TUB-1 Accession Number: NP_495710.1 GI Number: 17536605 FASTA E value: 1e-107 Max Identical 49% Max Similar: 65% |
references
Cover Photo Credit
[1] Delsuc, F., Brinkmann, H., and Philippe, H. (2005). Phylogenomics and the Reconstruction of the Tree of Life. Nature Reviews Genetics, 6(5), 361. doi: 10.1038/nrg1603.
[2] Understanding Evolution: Homology.
[3] Understanding Evolution: Homologies and Analogies.
[4] Koonin, E.V. and Galperin, M.Y. Sequence-Evolution-Function: Computational Approaches in Comparative Genomics. Boston: Kluwer Academic; 2003. Chapter 2, Evolutionary Concept in Genetics and Genomics. Available from: http://www.ncbi.nlm.nih.gov/books/NBK20255/
[5] Ashrafi K., Chang F.Y., Watts J.L., Fraser A.G., Kamath R.S., Ahringer J., Ruvkun G. (2003). Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature, 421: 268. doi:10.1038/nature01279.
[1] Delsuc, F., Brinkmann, H., and Philippe, H. (2005). Phylogenomics and the Reconstruction of the Tree of Life. Nature Reviews Genetics, 6(5), 361. doi: 10.1038/nrg1603.
[2] Understanding Evolution: Homology.
[3] Understanding Evolution: Homologies and Analogies.
[4] Koonin, E.V. and Galperin, M.Y. Sequence-Evolution-Function: Computational Approaches in Comparative Genomics. Boston: Kluwer Academic; 2003. Chapter 2, Evolutionary Concept in Genetics and Genomics. Available from: http://www.ncbi.nlm.nih.gov/books/NBK20255/
[5] Ashrafi K., Chang F.Y., Watts J.L., Fraser A.G., Kamath R.S., Ahringer J., Ruvkun G. (2003). Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature, 421: 268. doi:10.1038/nature01279.
Site created by Rachael Baird.
Genetics 564 Assignment, Spring 2014
University of Wisconsin-Madison
Last Updated: 5-9-14
Genetics 564 Assignment, Spring 2014
University of Wisconsin-Madison
Last Updated: 5-9-14