ExtRamp: a novel algorithm for extracting the ramp sequence based on the tRNA adaptation index or relative codon adaptiveness

Miller, Justin; Brase, Logan; Ridge, Perry G.

doi:10.1093/nar/gky1193

Cited by 18 publications

(18 citation statements)

References 29 publications

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“…Although both transcription and translation seem to be mediated by an initial ramp, the ramps have opposite efficiency. While a ramp of translation efficiency has been shown to start with higher occurrence of non-optimally translated codons at the 5 -end as a mechanism to possibly reduce traffic jams of ribosome downstream in translation elongation 5,11,37,38 , a ramp of transcription efficiency found here starts with optimal codons to seemingly reduce the energy required for unwinding dsDNA. Thus, the ramps of transcription and translation efficiency appear complementary in prokaryotes.…”

Section: Discussionmentioning

confidence: 70%

Codon usage bias creates a ramp of hydrogen bonding at the 5′-end in prokaryotic ORFeomes

Villada

Duran

Lee

2019

Preprint

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Codon usage bias exerts control over a wide variety of molecular processes. The positioning of synonymous codons within coding sequences (CDSs) dictates protein expression by mechanisms such as local translation efficiency, mRNA Gibbs free energy, and protein co-translational folding. In this work, we explore how codon variants affect the position-dependent content of hydrogen bonding, which in turn influences energy requirements for unwinding double-stranded DNA. By analyzing over 14,000 bacterial, archaeal, and fungal ORFeomes, we found that Bacteria and Archaea exhibit an exponential ramp of hydrogen bonding at the 5 -end of CDSs, while a similar ramp was not found in Fungi. The ramp develops within the first 20 codon positions in prokaryotes, eventually reaching a steady carrying capacity of hydrogen bonding that does not differ from Fungi. Selection against uniformity tests proved that selection acts against synonymous codons with high content of hydrogen bonding at the 5 -end of prokaryotic ORFeomes. Overall, this study provides novel insights into the molecular feature of hydrogen bonding that is governed by the genetic code at the 5 -end of CDSs. A web-based application to analyze the position-dependent hydrogen bonding of ORFeomes has been developed and is publicly available (https: //juanvillada.shinyapps.io/hbonds/).

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Section: Discussionmentioning

confidence: 70%

Codon usage bias creates a ramp of hydrogen bonding at the 5′-end in prokaryotic ORFeomes

Villada

Duran

Lee

2019

Preprint

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“…Highly expressed genes also have a ramp of 30-50 slowly-translated, rare codons at the 5' end of most protein coding sequences (Tuller, et al 2010) that serves to evenly space ribosomes ) and reduce mRNA secondary structure (Goodman, et al 2013) at translation initiation. A comprehensive analysis of ramp sequences from all domains of life, as well as a method to extract ramp sequences from individual genes is presented in Miller, Brase, et al (2019).…”

Section: Biological Implications Of Codon Usage Bias a Selection Towmentioning

confidence: 99%

How Codon Usage Bias Affects Our Ability to Recover the Tree of Life

Miller¹,

Whiting²,

Kauwe³

et al. 2019

Preprint

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Phylogenies depict shared evolutionary patterns and structures on a tree topology, enabling the identification of hierarchical and historical relationships. Recent analyses indicate that phylogenetic signals extend beyond the primary structure of protein or DNA, and various aspects of codon usage biases are phylogenetically conserved. Several functional biases exist within genes, including the number of codons that are used, the position of the codons, and the overall nucleotide composition of the genome. Codon usage biases can significantly affect transcription and translational efficiencies, leading to differential gene expression. Although systematic codon usage biases originate from the overall GC content of a species, ramp sequences, codon aversion, codon pairing, and tRNA competition also significantly affect gene expression and are phylogenetically conserved. We review recent advances in analyzing codon usage biases and their implications in phylogenomics. We first outline common phylogenomic techniques. Next, we identify several codon usage biases and their effects on secondary structure, gene expression, and implications in phylogenetics. Finally, we suggest how codon usage biases can be included in phylogenomics. By incorporating various codon usage biases in common phylogenomic algorithms, we propose that we can significantly improve tree inference. Since codon usage biases have significant biological implications, they should be considered in conjunction with other phylogenetic algorithms.

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“…We recently developed an algorithm, ExtRamp, to identify ramp sequences [14]. Previously, ramp sequences were known and characterized in only a few model species.…”

Section: Introductionmentioning

confidence: 99%

“…If an outlier portion is present at the beginning of the gene, it is considered a ramp sequence. Using this algorithm, species in most domains of life were shown to have an average of 10% of genes with ramp sequences [14]. Given the widespread presence of ramp sequences in most domains of life and their role in regulating translation, this project investigates the hypothesis that the presence or absence of a ramp sequence in a gene may be used as a morphological genomic character that can be used to recover a phylogenetic signal.…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Analysis of the Phylogenetic Signal in Ramp Sequences in 211 Vertebrates

McKinnon

Miller

Whiting

et al. 2020

Preprint

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Background: Ramp sequences increase translational speed and accuracy when rare, slowly-translated codons are found at the beginnings of genes. Here, the results of the first analysis of ramp sequences in a phylogenetic construct are presented.Methods: Ramp sequences were compared from 211 vertebrates (110 Mammalian and 101 non-mammalian). The presence and absence of ramp sequences was analyzed as a binary character in a parsimony and maximum likelihood framework. Additionally, ramp sequences were mapped to the Open Tree of Life taxonomy to determine the number of parallelisms and reversals that occurred, and these results were compared to what would be expected due to random chance. Lastly, aligned nucleotides in ramp sequences were compared to the rest of the sequence in order to examine possible differences in phylogenetic signal between these regions of the gene.Results: Parsimony and maximum likelihood analyses of the presence/absence of ramp sequences recovered phylogenies that are highly congruent with established phylogenies. Additionally, the retention index of ramp sequences is significantly higher than would be expected due to random chance (p-value = 0). A chi-square analysis of completely orthologous ramp sequences resulted in a pvalue of approximately zero as compared to random chance.Discussion: Ramp sequences recover comparable phylogenies as other phylogenomic methods. Although not all ramp sequences appear to have a phylogenetic signal, more ramp sequences track speciation than expected by random chance. Therefore, ramp sequences may be used in conjunction with other phylogenomic approaches.

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ExtRamp: a novel algorithm for extracting the ramp sequence based on the tRNA adaptation index or relative codon adaptiveness

Cited by 18 publications

References 29 publications

Codon usage bias creates a ramp of hydrogen bonding at the 5′-end in prokaryotic ORFeomes

Codon usage bias creates a ramp of hydrogen bonding at the 5′-end in prokaryotic ORFeomes

How Codon Usage Bias Affects Our Ability to Recover the Tree of Life

A Comprehensive Analysis of the Phylogenetic Signal in Ramp Sequences in 211 Vertebrates

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