molecular evolutionary analysis of abcb5 the ancestral gene is a full transporter with potentially deleterious single nucleotide polymorphismsabcb5祖先基因的分子进化分析是一个完整的运输与潜在的有害的单核苷酸多态性.pdfVIP

Molecular Evolutionary Analysis of ABCB5: The Ancestral Gene Is a Full Transporter with Potentially Deleterious Single Nucleotide Polymorphisms . . Karobi Moitra , Mark Scally , Kate McGee, Germaine Lancaster, Bert Gold, Michael Dean* Laboratory of Experimental Immunology, Human Genetics Section, Cancer and Inflammation Program, National Cancer Institute at Frederick, Frederick, Maryland, United States of America 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 posses 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. Methodology/Principal Findings: 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/Significance: From our in-silco an