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Deciphering the rationale behind specific codon usage pattern in extremophiles.

ABSTRACT: Protein stability is affected at different hierarchies - gene, RNA, amino acid sequence and structure. Gene is the first level which contributes via varying codon compositions. Codon selectivity of an organism differs with normal and extremophilic milieu. The present work attempts at detailing the codon usage pattern of six extremophilic classes and their harmony. Homologous gene datasets of thermophile-mesophile, psychrophile-mesophile, thermophile-psychrophile, acidophile-alkaliphile, halophile-nonhalophile and barophile-nonbarophile were analysed for filtering statistically significant attributes. Relative abundance analysis, 1-9 scale ranking, nucleotide compositions, attribute weighting and machine learning algorithms were employed to arrive at findings. AGG in thermophiles and barophiles, CAA in mesophiles and psychrophiles, TGG in acidophiles, GAG in alkaliphiles and GAC in halophiles had highest preference. Preference of GC-rich and G/C-ending codons were observed in halophiles and barophiles whereas, a decreasing trend was reflected in psychrophiles and alkaliphiles. GC-rich codons were found to decrease and G/C-ending codons increased in thermophiles whereas, acidophiles showed equal contents of GC-rich and G/C-ending codons. Codon usage patterns exhibited harmony among different extremophiles and has been detailed. However, the codon attribute preferences and their selectivity of extremophiles varied in comparison to non-extremophiles. The finding can be instrumental in codon optimization application for heterologous expression of extremophilic proteins.

SUBMITTER: Khan MF

PROVIDER: S-EPMC6195531 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Deciphering the rationale behind specific codon usage pattern in extremophiles.

Khan Mohd Faheem MF Patra Sanjukta S

Scientific reports 20181019 1

Protein stability is affected at different hierarchies - gene, RNA, amino acid sequence and structure. Gene is the first level which contributes via varying codon compositions. Codon selectivity of an organism differs with normal and extremophilic milieu. The present work attempts at detailing the codon usage pattern of six extremophilic classes and their harmony. Homologous gene datasets of thermophile-mesophile, psychrophile-mesophile, thermophile-psychrophile, acidophile-alkaliphile, halophil ...[more]

PMID: 30341344

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Project description:BackgroundGene expression is highly variable across tissues of multi-cellular organisms, influencing the codon usage of the tissue-specific transcriptome. Cancer disrupts the gene expression pattern of healthy tissue resulting in altered codon usage preferences. The topic of codon usage changes as they relate to codon demand, and tRNA supply in cancer is of growing interest.MethodsWe analyzed transcriptome-weighted codon and codon pair usage based on The Cancer Genome Atlas (TCGA) RNA-seq data from 6427 solid tumor samples and 632 normal tissue samples. This dataset represents 32 cancer types affecting 11 distinct tissues. Our analysis focused on tissues that give rise to multiple solid tumor types and cancer types that are present in multiple tissues.ResultsWe identified distinct patterns of synonymous codon usage changes for different cancer types affecting the same tissue. For example, a substantial increase in GGT-glycine was observed in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed invasive ductal and lobular carcinoma (IDLC) of the breast. Change in synonymous codon preference favoring GGT correlated with change in synonymous codon preference against GGC in IDC and IDLC, but not in ILC. Furthermore, we examined the codon usage changes between paired healthy/tumor tissue from the same patient. Using clinical data from TCGA, we conducted a survival analysis of patients based on the degree of change between healthy and tumor-specific codon usage, revealing an association between larger changes and increased mortality. We have also created a database that contains cancer-specific codon and codon pair usage data for cancer types derived from TCGA, which represents a comprehensive tool for codon-usage-oriented cancer research.ConclusionsBased on data from TCGA, we have highlighted tumor type-specific signatures of codon and codon pair usage. Paired data revealed variable changes to codon usage patterns, which must be considered when designing personalized cancer treatments. The associated database, CancerCoCoPUTs, represents a comprehensive resource for codon and codon pair usage in cancer and is available at https://dnahive.fda.gov/review/cancercocoputs/ . These findings are important to understand the relationship between tRNA supply and codon demand in cancer states and could help guide the development of new cancer therapeutics.

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Deciphering the rationale behind specific codon usage pattern in extremophiles.

Publications

Deciphering the rationale behind specific codon usage pattern in extremophiles.

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