Genomic Conservation of the Outer Hair Cell Motility Protein, Prestin in the Monotreme: Ornithorhyncus anatinus (Platypus)
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Authors
Sanjeevi, Divvya C.
Issue Date
2007-08
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Thesis
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en_US
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Abstract
The process of outer hair cell (OHC) motility, which enables sound amplification, is an active process that is thought to be unique to mammals. Prestin, the motor protein of these OHCs, is crucial for its function in mammals. Loss of prestin has been found to result in a high-frequency hearing loss of 40 to 60 dB (sensitivity) in mice (Liberman et ai, 2002). Since being isolated in gerbil outer hair cells in 2001 (Zheng et al), prestin's exact tertiary structure remains to be elucidated. Also, the nature of its function, as either translocater or transporter, needs to be clarified.
The monotremes are unique in their shared cochlear features to mammals, birds and reptiles The presence of a prestin ortholog in a highly divergent mammal such as the Omithorhynchus anatinus (platypus) would indicate the preservation of function The absence of a prestin ortholog would allow for comparisons among the genomes, to identify how and when prestin evolved, using bioinformatics. In this study, the bioinformatics approach consisted of stringent criteria in ortholog identification based on 1) gene organization, 2) synteny, 3) structural motifs and 4) nucleotide and amino acid homology.
A prestin ortholog was identified in the platypus with a great identity to the mammalian mouse prestin. The eutherian branches have a 96% identity and 98% shared similarity in prestin amino acid structure, with the variations primarily in the C' and N' terminus. Mammalian prestin orthologs have "conserved motifs" throughout the entire length that may be crucial for function. In general, the conservation of prestin is greater than its sister paralogs, SIc26a6 or Slc26a4, which may signify its crucial function in mammalian outer hair cells. There is indication, even in the primary amino acid sequence comparisons, that its functionality is likely to vary between mammals and non-mammals.
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Creighton University
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Thesis-Divvya Sanjeevi.pdf