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Phylogenetic and promoter analysis of islet amyloid polypeptide gene causing type 2 diabetes in mammalian species

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Abstract

Mutation in islet amyloid polypeptide (IAPP) gene results into its protein misfolding and fibril formation. Isolation of various mammalian species shows its conservation from 89- to 93-amino acid sequence sharing homology with cats, rats, mice, and guinea pigs. For the present study, detailed phylogenetic analysis is carried out for the upstream promoter region of IAPP gene, IAPP messenger RNA (mRNA), and proIAPP protein of nine mammalian species. Sequence analysis has shown partial conservation among the rodent species and the canidae group; however, the primate group species has shown maximum conservation of all sequences under considerations with respect to the human IAPP sequences. Our novel approach of analyzing mRNA and protein sequence conservation of proIAPP delineates the importance for developing IAPP models in closely related species sharing a common ancestor with the time divergence. Further, transcription factor binding sites were critically analyzed for the upstream promoter region of the IAPP gene. These probable binding sites were predicted for DNA motifs recognized by transcription factors, which may prove to be helpful in predicting the regulatory mechanism in understanding the regulation of IAPP gene under in vitro or in vivo conditions. Therefore, confirming the co-evolutionary relationship of IAPP among different species will help us guide in studying transcription factor binding site for poorly studied IAPP gene and targeting disease mutation initiating pancreatic amyloidosis in clinical applications. The phylogenetic and gene promoter analysis presented in the paper reveals regulatory elements for beta cell death caused by pancreatic amyloidosis and resulting in type 2 diabetes (T2D) onset.

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  1. Chitkara School of Health Sciences, Chitkara University, Punjab, India

    Varsha Singh

  2. Chitkara University Research and Innovation Network, Chitkara University, Punjab, India

    Nitin Saluja

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Singh, V., Saluja, N. Phylogenetic and promoter analysis of islet amyloid polypeptide gene causing type 2 diabetes in mammalian species. Int J Diabetes Dev Ctries 36, 477–489 (2016). https://doi.org/10.1007/s13410-016-0508-3

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