Oncotarget

Research Papers:

S18 family of mitochondrial ribosomal proteins: evolutionary history and Gly132 polymorphism in colon carcinoma

Muhammad Mushtaq, Raja Hashim Ali, Vladimir Kashuba, George Klein and Elena Kashuba _

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Oncotarget. 2016; 7:55649-55662. https://doi.org/10.18632/oncotarget.10957

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Abstract

Muhammad Mushtaq1, Raja Hashim Ali2, Vladimir Kashuba1,3, George Klein1, Elena Kashuba1,4

1Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institute, Stockholm, S-17177, Sweden

2KTH Royal Institute of Technology, Science for Life Laboratory, School of Computer Science and Communication, Solna, SE-17 177, Sweden

3Institute of Molecular Biology and Genetics of NASU, Kyiv, 03680, Ukraine

4R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, Kyiv, 03022, Ukraine

Correspondence to:

Elena Kashuba, email: [email protected]

Keywords: mitochondrial ribosomal proteins, MRPS18 family, phylogenetic analysis, evolutionary trace analysis, genetic polymorphism

Received: April 07, 2016    Accepted: July 10, 2016    Published: July 30, 2016

ABSTRACT

S18 family of mitochondrial ribosomal proteins (MRPS18, S18) consists of three members, S18-1 to -3. Earlier, we found that overexpression of S18-2 protein resulted in immortalization and eventual transformation of primary rat fibroblasts. The S18-1 and -3 have not exhibited such abilities. To understand the differences in protein properties, the evolutionary history of S18 family was analyzed. The S18-3, followed by S18-1 and S18-2 emerged as a result of ancient gene duplication in the root of eukaryotic species tree, followed by two metazoan-specific gene duplications. However, the most conserved metazoan S18 homolog is the S18-1; it shares the most sequence similarity with S18 proteins of bacteria and of other eukaryotic clades. Evolutionarily conserved residues of S18 proteins were analyzed in various cancers. S18-2 is mutated at a higher rate, compared with S18-1 and -3 proteins. Moreover, the evolutionarily conserved residue, Gly132 of S18-2, shows genetic polymorphism in colon adenocarcinomas that was confirmed by direct DNA sequencing.

Concluding, S18 family represents the yet unexplored important mitochondrial ribosomal proteins.


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PII: 10957