This page was produced as an assignment for Genetics 677, an undergraduate course at UW - Madison.
The Study of Homology
Gene homology refers to genes in different species that have been inherited from a common ancestor [1]. Homologous genes can also be considered orthologous if they have also retained the same function throughout time as well. Homology/orthology should not be confused with analogy, which refers to two genes of the same function but evolved separately and independently from each other [1,2].
So why study homology? So what if a fly has the same gene as a human? Well, this has a couple of implications. First of all, it is great news if a model organism (such as a fruit fly or a mouse) has the same gene as a human, because it makes it possible - ethically, chronologically, and financially - to study that gene to a higher degree than would be possible to study in humans. Secondly, if a gene is conserved (that is, virtually unchanged, especially in function, throughout the course of evolution) in organisms from humans to fruit flies, it shows that the gene is probably involved in an important and/or necessary pathway or process [3]. A classic example of a highly conserved set of genes are Hox genes, which help control development and body plans, and are present in animals from worms to humans and everything in between [4].
So why study homology? So what if a fly has the same gene as a human? Well, this has a couple of implications. First of all, it is great news if a model organism (such as a fruit fly or a mouse) has the same gene as a human, because it makes it possible - ethically, chronologically, and financially - to study that gene to a higher degree than would be possible to study in humans. Secondly, if a gene is conserved (that is, virtually unchanged, especially in function, throughout the course of evolution) in organisms from humans to fruit flies, it shows that the gene is probably involved in an important and/or necessary pathway or process [3]. A classic example of a highly conserved set of genes are Hox genes, which help control development and body plans, and are present in animals from worms to humans and everything in between [4].
Finding the Homologs of the pah Gene
Homologs were found using NCBI's BLAST (Basic Local Alignment Search Tool) program. The BLAST program takes inputs of sequences (such as mRNA, DNA, or protein sequences), compares them to a database of other sequences and genomes, and finds similar sequences. This program uses a set of algorithms and statistics to create alignments (areas of the sequence that match each other) and to predict how identical the sequences are overall. BLAST is a good starting place to find homologs - inputting a sequence of interest (such as the human pah gene) and running it through the program will provide a list of potentially homologous genes in other species, based upon how identical the sequences are. Then, running the two potentially homologous genes against each other allows for analyzing alignments more finely. HomoloGene is another useful tool, which provides information on the known homologs of a specific gene of interest.
Because of the variety and amount of non-coding sequence in the pah gene (there are 12 introns), it was not possible to perform a BLAST search using DNA. Therefore, only coding information was used by BLASTing pah mRNA sequences.
Because of the variety and amount of non-coding sequence in the pah gene (there are 12 introns), it was not possible to perform a BLAST search using DNA. Therefore, only coding information was used by BLASTing pah mRNA sequences.
Analysis
Comparing the similarities between the genes, we can see that the human pah gene is all but identical with its homolog in the chimpanzee. This makes sense, as chimpanzees are humans' closest evolutionary relatives. The order of similarity (chimpanzee, mouse, chicken, zebrafish, fruit fly, and nematode) also can be considered intuitive, as all the mammals are more similar to the human pah gene than the other animals, and all the vertebrates are more similar than the non-vertebrates. Additionally, the similarity between all of the genes shows that pah is conserved throughout the animal kingdom. The low E values (shown below) also shows that these results are statistically significant, which allows inference that these genes are all homologs and not analogs. There were no homologs to the pah gene in non-animal organisms, such as E. coli, S. cerevisiae (yeast), and Arabidopsis.
Homolog Reference Pages and Numbers
Chimpanzee (Pan troglodytes) - Phenylalanine Hydroxylase
Accession Number: NC_006479.3 GI Number: 291061364 FASTA E value: 0.0 Max identical: 99.7% Chicken (Gallus gallus) - Phenylalanine Hydroxylase
Accession Number: NC_006088.3 GI Number: 358485511 FASTA E value: 0.0 Max identical: 77.1% Zebrafish (Danio rerio) - Phenylalanine Hydroxylase
Accession Number: NC_007115.5 GI Number: 312144726 FASTA E value: 0.0 Max identical: 70.0% |
Mouse (Mus musculus) - Phenylalanine Hydroxylase
Accession Number: NC_000076.6 GI Number: 372099100 FASTA E value: 0.0 Max identical: 87.2% Nematode (Caenorhabditis elegans) - Phenylalanine Hydroxylase
Accession Number: NC_003280.9 GI Number: 392973738 FASTA E value: 2 e-50 Max identical: 57.8% Fruit Fly (Drosophila melanogaster) - Henna
Accession Number: NT_037436.3 GI Number: 116010443 FASTA E value: 5 e-122 Max identical: 63.7% |
pah_mrna_alignments.webarchive | |
File Size: | 30 kb |
File Type: | webarchive |
References
1. Delsuc F, Brinkmann H, Philippe H. Phylogenomics and the reconstruction of the tree of life. Nat Rev Genet. 2005 May;6(5):361-75. Review. PubMed PMID: 15861208.
2. J. H. Jackson Laboratory. "Gene Similarity: Some Definitions." Michigan State University, 08 Apr. 1999. Web. <https://www.msu.edu/~jhjacksn/Reports/similarity.htm>.
3. Brody, Thomas B., PhD. "Evolutionarily Conserved Developmental Pathways." The Interactive Fly. Society for Developmental Biology, 10 Feb. 2012. Web. 15 Feb. 2013. <http://www.sdbonline.org/fly/aimain/aadevinx.htm>.
4. Lemons D, McGinnis W. Genomic evolution of Hox gene clusters. Science. 2006 Sep 29;313(5795):1918-22. Review. PubMed PMID: 17008523.
2. J. H. Jackson Laboratory. "Gene Similarity: Some Definitions." Michigan State University, 08 Apr. 1999. Web. <https://www.msu.edu/~jhjacksn/Reports/similarity.htm>.
3. Brody, Thomas B., PhD. "Evolutionarily Conserved Developmental Pathways." The Interactive Fly. Society for Developmental Biology, 10 Feb. 2012. Web. 15 Feb. 2013. <http://www.sdbonline.org/fly/aimain/aadevinx.htm>.
4. Lemons D, McGinnis W. Genomic evolution of Hox gene clusters. Science. 2006 Sep 29;313(5795):1918-22. Review. PubMed PMID: 17008523.