Evolution of ABCA4 proteins in vertebrates

Alexander N. Yatsenko, Wojciech Wiszniewski, Charles M. Zaremba, Milan Jamrich, James R. Lupski

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


The ABCA4 (ABCR) gene encodes a retinal-specific ATP-binding cassette transporter. Mutations in ABCA4 are responsible for several recessive macular dystrophies and susceptibility to age related macular degeneration (AMD). The protein appears to function as a flippase of all-trans-retinaldehyde and/or its derivatives across the membrane of outer segment disks and is a potentially important element in recycling visual cycle metabolites. However, the understanding of ABCA4's role in the visual cycle is limited due to the lack of a direct functional assay. An evolutionary analysis of ABCA4 may aid in the identification of conserved elements, the preservation of which implies functional importance. To date, only human, murine, and bovine ABCA4 genes are described. We have identified ABCA4 genes from African (Xenopus laevis) and Western (Silurana tropicalis) clawed frogs. A comparative analysis describing the evolutionary relationships between the frog ABCA4s, annotated T. rubripes ABCA4, and mammalian ABCA4 proteins was carried out. Several segments are conserved in both intradiscal loop (IL) domains, in addition to the transmembrane and ATP-binding domains. Nonconserved segments were found in the IL and cytoplasmic linker domains. Maximum likelihood analyses of the aligned sequences strongly suggest that ABCA4 was subject to purifying selection. Collectively, these data corroborate the current evolutionary model where two distinct ABCA half-transporter progenitors were combined to form a full ABCA4 progenitor in ancestral chordates. We speculate that evolutionary alterations may increase the retinoid metabolite recycling capacity of ABCA4 and may improve dark adaptation.

Original languageEnglish (US)
Pages (from-to)72-80
Number of pages9
JournalJournal of Molecular Evolution
Issue number1
StatePublished - Jan 2005
Externally publishedYes


  • ABCA4
  • Conserved regions
  • Photoreceptor
  • Phylogenetic tree
  • Selection

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics


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