This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
Evolutionary conservation of ABC transporter proteins
ABC transporter families across multiple species [2]. Click image to enlarge and view key.
An ancient group of proteins...
Members of the large, ancient ABC transporter superfamily are found in many species in all three kingdoms [1].
Functions of ABC transporters...
ABC transporters perform active transport (that is, requiring energy from dephosphorylation of ATP) of large or polar molecules across cell membranes. These include ions, sugars, lipids, sterols, peptides and proteins, none of which can cross the non-polar membrane by diffusion alone [1].
Roles in human disease...
In humans, members of the ABC transporter superfamily are believed to play a role in the development of many diseases, including cystic fibrosis and certain cancers [2][7]. In both cases, mutated ABC transporters become unable to either take up of effuse molecules from cells, as is also the case with Tangier disease.
ABC1 homologs in eukaryotes
Known protein homologs of human ABCA1 in eukaryotes [3]
The ABC1 protein has well characterized homologs in several eukaryotic species. Their gene names and protein accession numbers can be found in the table above [3].
Protein phylogeny - BioNJ (bootstrapping)
TreeDyn [5] tree generated for ABC1 homologs in five mammalian species aligned using BioNJ [4]
Alignment with BioNJ and tree-drawing with TreeDyn 198.3 [5] among the protein sequences of five mammals with 1, 5 and 10 bootstrap trees produced the same phylogeny, pictured here.
The species used include human (Homo sapiens), common chimpanzee (Pan troglodytes), domestic dog (Canis lupis familiaris), domestic cow (Bos taurus) and mouse (Mus musculus). Comparisons were restricted to these species because the program requires that the compared protein sequences be of equal length - in this case, 2,661 AA. [4]
The species used include human (Homo sapiens), common chimpanzee (Pan troglodytes), domestic dog (Canis lupis familiaris), domestic cow (Bos taurus) and mouse (Mus musculus). Comparisons were restricted to these species because the program requires that the compared protein sequences be of equal length - in this case, 2,661 AA. [4]
Protein phylogeny - MrBayes 3.1.2
(Bayesian analysis)
TreeDyn [5] tree generated for ABC1 homologs in the same five mammalian species aligned using MrBayes [6]
When the same amino acid sequences are run through the MrBayes 3.1.2 program, which uses a Bayesian analysis algorithm instead of bootstrapping tests to generate a phylogeny, the same tree is produced.
The agreement between these two different approaches to generating phylogenies strongly indicates that the evolutionary relationships they suggest are correct.
The agreement between these two different approaches to generating phylogenies strongly indicates that the evolutionary relationships they suggest are correct.
Protein sequence file used for BioNJ and MrBayes alignments
A .txt. file of the protein sequence alignment file used to generate the BioNJ tree shown at right is available for download at below.
| bionjalignment.txt |
Sources:
1. http://www.ncbi.nlm.nih.gov/books/NBK31/
2. Moitra K, Scally M, McGee K, Lancaster G, Gold B, et al. 2011 Molecular Evolutionary Analysis of ABCB5: The Ancestral Gene Is a Full Transporter with Potentially Deleterious Single Nucleotide Polymorphisms. PLoS ONE 6(1): e16318. doi:10.1371/journal.pone.0016318.
3. http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=homologene&dopt=MultipleAlignment&list_uids=21130
4. http://www.phylogeny.fr/version2_cgi/one_task.cgi?task_type=bionj
5. http://www.phylogeny.fr/version2_cgi/one_task.cgi?task_type=treedyn
6. http://www.phylogeny.fr/version2_cgi/one_task.cgi?task_type=mrbayes
7. Dean M, Rzhetsky A, Allikmets R. The Human ATP-Binding Cassette (ABC) Transporter Superfamily. Genome Research. 2001; 11:1156-1166.
1. http://www.ncbi.nlm.nih.gov/books/NBK31/
2. Moitra K, Scally M, McGee K, Lancaster G, Gold B, et al. 2011 Molecular Evolutionary Analysis of ABCB5: The Ancestral Gene Is a Full Transporter with Potentially Deleterious Single Nucleotide Polymorphisms. PLoS ONE 6(1): e16318. doi:10.1371/journal.pone.0016318.
3. http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=homologene&dopt=MultipleAlignment&list_uids=21130
4. http://www.phylogeny.fr/version2_cgi/one_task.cgi?task_type=bionj
5. http://www.phylogeny.fr/version2_cgi/one_task.cgi?task_type=treedyn
6. http://www.phylogeny.fr/version2_cgi/one_task.cgi?task_type=mrbayes
7. Dean M, Rzhetsky A, Allikmets R. The Human ATP-Binding Cassette (ABC) Transporter Superfamily. Genome Research. 2001; 11:1156-1166.
