This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison
Gene Homology
Homology is an indication of how similar two gene sequences compare to each other. Generally, genes will be more similar to each other when they are more closely related and have more recent common ancestors. Homology can be an important tool in the study of genes because it can indicate which genes are more important than others based on what sequences are more highly conserved throughout evolution. It can also be used to study disease, when changes in the sequence of a gene cause a similar phenotypic response in many species [1].
The human SLC6A4 gene can be described as follows:
The human SLC6A4 gene can be described as follows:
Homo sapiens (Human)
Solute carrier family 6 (neurotransmitter transporter), member 4 (SLC6A4)
Accession Number: NM_001045.5
Length: 6,615 bp
Solute carrier family 6 (neurotransmitter transporter), member 4 (SLC6A4)
Accession Number: NM_001045.5
Length: 6,615 bp
Analysis
Homologs of SLC6A4 were initially found by searching through the NCBI Basic Local Alignment Search Tool (BLAST). Since this study is on gene homologs, a nucleotide blast was selected. With the accession number of the human SLC6A4 already known, the homo sapiens sequence can be compared to any organisms that are also found in the database. Fifteen homologs were found by searching highly similar sequences with Megablast, and their accession numbers as well as their similarity to the homo sapiens gene were noted.
Each of these homologs was confirmed by performing a reciprocal BLAST. This involves using the homolog accession number to search for homo sapiens homologs. If SLC6A4 was found to be a homolog with the same similarity to that found in the original BLAST, the two were considered true homologs.
A second site, HomoloGene, was used to search for more homologs and confirm those found using BLAST. Not all fifteen were found on HomoloGene, but of those that were found, all matched the genes found in BLAST. Two more homologs listed in HomoloGene, X. tropicalis and D. rerio, were not found using BLAST in the original search. Since these are common model organisms, a second Blast search was performed for these two organisms using sequences that were only somewhat similar (blastn). Under the less stringent search conditions, both organisms were found resulting in seventeen model organisms for comparison. These genes and their descriptions are listed below.
Pan troglodytes (Chimpanzee)
solute carrier family 6 (neurotransmitter transporter), member 4 (SLC6A4) Accession Number: XM_001135066.3 Max Identical: 99% Loxodonta africana (Elephant)
solute carrier family 6 (neurotransmitter transporter), member 4 (SLC6A4) Accession Number: XM_003416785.2 Max Identical: 88% Canis lupus familiaris (Dog)
solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (SLC6A4) Accession Number: XM_005624348.1 Max Identical: 86% Mus musculus (Mouse)
Solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (Slc6a4) Accession Number: NM_010484.2 Max Identical: 83% Gallus gallus (Chicken)
solute carrier family 6 (neurotransmitter transporter), member 4 (SLC6A4) Accession Number: NM_213572.1 Max Identical: 79% Xenopus tropicalis (Frog)
sodium-dependent serotonin transporter-like (LOC100493853) Accession Number: XM_002943375.2 Max Identical: 76% |
Macaca mulatta (Rhesus Macaque)
solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (SLC6A4) Accession Number: NM_001032823.1 Max Identical: 96% Equus ferus caballus (Domestic Horse)
serotonin transporter (5HTT) Accession Number: NM_001081824.1 Max Identical: 87% Cricetulus griseus (Chinese Hamster)
solute carrier family 6 (neurotransmitter transporter), member 4 (Slc6a4) Accession Number: XM_003506082.2 Max Identical: 84% Taeniopygia guttata (Zebra Finch)
solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (SLC6A4) Accession Number: XM_004186239.1 Max Identical: 80% Drosophila melanogaster (Fruit Fly)
serotonin transporter (SerT) Accession Number: NM_001299910.1 Max Identical: 76% Danio rerio (Zebrafish)
solute carrier family 6 (neurotransmitter transporter), member 4a (slc6a4a) Accession Number: NM_001039972.1 Max Identical: 72% |
Felis catus (Cat)
solute carrier family 6 (neurotransmitter transporter), member 4 (SLC6A4) Accession Number: XM_006940005.1 Max Identical: 88% Bos Taurus (Cattle)
solute carrier family 6 (neurotransmitter transporter), member 4 (SLC6A4) Accession Number: NM_174609.2 Max Identical: 87% Rattus norvegicus (Brown Rat)
solute carrier family 6 (neurotransmitter transporter), member 4 (Slc6a4) Accession Number: XM_008767950.1 Max Identical: 84% Columba livia (Dove)
solute carrier family 6 (neurotransmitter transporter), member 4 (SLC6A4) Accession Number: XM_005502033.1 Max Identical: 79% Culex quinquefasciatus (Mosquito)
sodium-dependent serotonin transporter Accession Number: XM_001849899.1 Max Identical: 76% |
Figure 1: Graphical representation of SLC6A4 gene homology, with the most similar at the bottom and least similar at the top.
Discussion
SLC6A4 is highly conserved in the organisms above. This is important to note, because it suggests this is an important gene whose resulting protein serves an essential function. A notable observation is that SLC6A4 is only expressed in multi-cellular organisms in the kingdom Animalia. No plants or fungi have similar sequences. This makes sense because SLC6A4 is involved in neurotransmission and neuronal systems are not found in organisms outside of Animalia. Within the animals, those organisms that are more closely related to humans evolutionarily show the highest sequence similarity to the human SLC6A4 gene while the insects, fish, and amphibians have the least similar sequences. This is expected, as organisms that have more recently diverged from each other should have more similar genomes than those that diverged in the distant past.
References
[1] Homologies. (n.d.). Retrieved March 21, 2015, from http://evolution.berkeley.edu/evolibrary/article/lines_04
BLAST: http://blast.ncbi.nlm.nih.gov/Blast.cgi
HomoloGene: http://www.ncbi.nlm.nih.gov/homologene/817
BLAST: http://blast.ncbi.nlm.nih.gov/Blast.cgi
HomoloGene: http://www.ncbi.nlm.nih.gov/homologene/817