title: Molecular evolutionary analysis of ABCB5: the ancestral gene is a full transporter with potentially deleterious single nucleotide polymorphisms.
abstract: BACKGROUND
  ABCB5 is a member of the ABC protein superfamily, which includes the transporters ABCB1, ABCC1 and ABCG2 responsible for causing drug resistance in cancer patients and also several other transporters that have been linked to human disease. The ABCB5 full transporter (ABCB5.ts) is expressed in human testis and its functional significance is presently unknown. Another variant of this transporter, ABCB5 beta possess a "half-transporter-like" structure and is expressed in melanoma stem cells, normal melanocytes, and other types of pigment cells. ABCB5 beta has important clinical implications, as it may be involved with multidrug resistance in melanoma stem cells, allowing these stem cells to survive chemotherapeutic regimes.
  
  
  RESULTS
  We constructed and examined in detail topological structures of the human ABCB5 protein and determined in-silico the cSNPs (coding single nucleotide polymorphisms) that may affect its function. Evolutionary analysis of ABCB5 indicated that ABCB5, ABCB1, ABCB4, and ABCB11 share a common ancestor, which began duplicating early in the evolutionary history of chordates. This suggests that ABCB5 has evolved as a full transporter throughout its evolutionary history.
  
  
  CONCLUSIONS
  From our in-silco analysis of cSNPs we found that a large number of non-synonymous cSNPs map to important functional regions of the protein suggesting that these SNPs if present in human populations may play a role in diseases associated with ABCB5. From phylogenetic analyses, we have shown that ABCB5 evolved as a full transporter throughout its evolutionary history with an absence of any major shifts in selection between the various lineages suggesting that the function of ABCB5 has been maintained during mammalian evolution. This finding would suggest that ABCB5 beta may have evolved to play a specific role in human pigment cells and/or melanoma cells where it is predominantly expressed.
authors.affiliation: Laboratory of Experimental Immunology, Human Genetics Section, Cancer and Inflammation Program, National Cancer Institute at Frederick, Frederick, Maryland, United States of America.
authors.forename: Karobi
authors.initials: K
authors.lastname: Moitra
authors.forename: Mark
authors.initials: M
authors.lastname: Scally
authors.forename: Kate
authors.initials: K
authors.lastname: McGee
authors.forename: Germaine
authors.initials: G
authors.lastname: Lancaster
authors.forename: Bert
authors.initials: B
authors.lastname: Gold
authors.forename: Michael
authors.initials: M
authors.lastname: Dean
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000502:physiology; D000818:Animals; D043344:Chordata / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D008544:Melanocytes / Q000737:chemistry; D008545:Melanoma / Q000737:chemistry / Q000235:genetics; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide
chemical_list: C480744:ABCB5 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1