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The RAS subfamily Evolution – tracing evolution for its utmost exploitation

In the development of multicellularity, signaling proteins has played a very important role. Among them, RAS family is one of the most widely studied protein family. However, evolutionary analysis has been carried out mainly on super family level leaving sub family information in scanty. Thus, a sub...

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Detalles Bibliográficos
Autores principales: Saad, Ismail IF, Saha, Saurav B, Thomas, George
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Biomedical Informatics 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070039/
https://www.ncbi.nlm.nih.gov/pubmed/24966537
http://dx.doi.org/10.6026/97320630010293
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author Saad, Ismail IF
Saha, Saurav B
Thomas, George
author_facet Saad, Ismail IF
Saha, Saurav B
Thomas, George
author_sort Saad, Ismail IF
collection PubMed
description In the development of multicellularity, signaling proteins has played a very important role. Among them, RAS family is one of the most widely studied protein family. However, evolutionary analysis has been carried out mainly on super family level leaving sub family information in scanty. Thus, a subfamily evolutionary study on RAS evolutionary expansion is imperative as it will aid in better drug designing against dreadful diseases like Cancer and other developmental diseases. The present study was aimed to understand RAS evolution on both holistic as well as reductive level. All human RAS family genes and protein were subjected to BLAST tools to find orthologs and paralogs with different parameters followed by phylogenetic tree generation. Our results clearly showed that H-RAS is the most primitive RAS in higher eukaryotes and then diverged into other RAS family members due to different gene modification events. Furthermore, a site specific selection pressure analysis was carried out using SELECTON server which showed that H-RAS, M-RAS and N-RAS are evolving faster than K-RAS and R-RAS. Thus, the results ascertain a new ground to cancer biologists to exploit negatively selected K-RAS and R-RAS as potent drug targets in cancer therapeutics.
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spelling pubmed-40700392014-06-25 The RAS subfamily Evolution – tracing evolution for its utmost exploitation Saad, Ismail IF Saha, Saurav B Thomas, George Bioinformation Hypothesis In the development of multicellularity, signaling proteins has played a very important role. Among them, RAS family is one of the most widely studied protein family. However, evolutionary analysis has been carried out mainly on super family level leaving sub family information in scanty. Thus, a subfamily evolutionary study on RAS evolutionary expansion is imperative as it will aid in better drug designing against dreadful diseases like Cancer and other developmental diseases. The present study was aimed to understand RAS evolution on both holistic as well as reductive level. All human RAS family genes and protein were subjected to BLAST tools to find orthologs and paralogs with different parameters followed by phylogenetic tree generation. Our results clearly showed that H-RAS is the most primitive RAS in higher eukaryotes and then diverged into other RAS family members due to different gene modification events. Furthermore, a site specific selection pressure analysis was carried out using SELECTON server which showed that H-RAS, M-RAS and N-RAS are evolving faster than K-RAS and R-RAS. Thus, the results ascertain a new ground to cancer biologists to exploit negatively selected K-RAS and R-RAS as potent drug targets in cancer therapeutics. Biomedical Informatics 2014-05-20 /pmc/articles/PMC4070039/ /pubmed/24966537 http://dx.doi.org/10.6026/97320630010293 Text en © 2014 Biomedical Informatics This is an open-access article, which permits unrestricted use, distribution, and reproduction in any medium, for non-commercial purposes, provided the original author and source are credited.
spellingShingle Hypothesis
Saad, Ismail IF
Saha, Saurav B
Thomas, George
The RAS subfamily Evolution – tracing evolution for its utmost exploitation
title The RAS subfamily Evolution – tracing evolution for its utmost exploitation
title_full The RAS subfamily Evolution – tracing evolution for its utmost exploitation
title_fullStr The RAS subfamily Evolution – tracing evolution for its utmost exploitation
title_full_unstemmed The RAS subfamily Evolution – tracing evolution for its utmost exploitation
title_short The RAS subfamily Evolution – tracing evolution for its utmost exploitation
title_sort ras subfamily evolution – tracing evolution for its utmost exploitation
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070039/
https://www.ncbi.nlm.nih.gov/pubmed/24966537
http://dx.doi.org/10.6026/97320630010293
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