Title

Low thymine content in PINK1 mRNAs and insights into Parkinson’s disease

Authors

Perumal Anandagopu, Shamima Banu, Jinyan Li^*

Affiliation

Bioinformatics Research Center, School of Computer Engineering, Nanyang Technological University, NS4-04-33a, 50 Nanyang Avenue, Singapore 639798

Email

jyli@ntu.edu.sg

Article Type

Hypothesis

Date

Received March 19, 2010; accepted April 09, 2010; published April 30, 2010

Abstract

Thymine is the only nucleotide base which is changed to uracil upon transcription, leaving mRNA less hydrophobic compared to its DNA counterpart. All the 16 codons that contain uracil (or thymine in gene) as the second nucleotide code for the five large hydrophobic residues (LHRs), namely phenylalanine, isoleucine, leucine, methionine and valine. Thymine content (i.e. the fraction of XTX codons, where X = A, C, G, or T) in PINK1 mRNA sequences and its relationship with protein stability and function are the focus of this work. This analysis will shed light on PINK1’s stability, thus a clue can be provided to understand the mitochondrial dysfunction and the failure of oxidative stress control frequently observed in Parkinson’s disease. We obtained the complete PINK1 mRNA sequences of 8 different species. The distributions of XTX codons in different frames are calculated. We observed that the thymine content reached the highest level in the coding frame 1 of the PINK1 mRNA sequence of Bos Taurus (Bt), that is peaked at 27%. Coding frame 1 containing low thymine leads to the reduction in LHRs in the corresponding proteins. Therefore, we conjecture that proteins from the other organisms, including Homo sapiens, lost some of their hydrophobicity and became susceptible to dysfunction. Genes such as PINK1 have reduced thymine in the evolutionary process thereby making their protein products potentially being susceptible to instability and causing disease. Adding more hydrophobic residues (thymine) at appropriate places might help conserve important biological functions.

Keywords

thymine distribution; PINK1; sequence analysis; protein stability; frame analysis

Citation

Anandagopu et al. Bioinformation 4(10): 000-000 (2010)

Edited by

P. Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.