Tamir Tuller - Academia.edu (original) (raw)

Papers by Tamir Tuller

Research paper thumbnail of Solving the riddle of the evolution of Shine-Dalgarno based translation in chloroplasts

The chloroplast, a photosynthetic organelle found in all plant and algae species, originates from... more The chloroplast, a photosynthetic organelle found in all plant and algae species, originates from an ancient event in which a cyanobacterium was engulfed by a larger eukaryote. Thus, modern chloroplasts still harbor a bacterial-like genome and carry out all stages of gene expression, including mRNA translation by a 70S ribosome. However, the Shine-Dalgarno model, which predominantly regulates translation initiation by base-pairing between the ribosomal RNA and the mRNA in model bacteria genera, was reported to have ambiguous effects on chloroplast gene expression. Here we show that while the Shine-Dalgarno motif is clearly conserved in proteobacterial mRNAs, its general absence from chloroplast mRNAs is observed in cyanobacteria as well, promoting the idea that the evolutionary process of reducing the centrality of the Shine-Dalgarno mechanism began well before plastid endosymbiosis. As plastid ribosomal RNA anti-Shine-Dalgarno elements are highly similar to their bacterial counterp...

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Research paper thumbnail of Computational discovery and modeling of novel gene expression rules encoded in the mRNA

Biochemical Society Transactions

The transcript is populated with numerous overlapping codes that regulate all steps of gene expre... more The transcript is populated with numerous overlapping codes that regulate all steps of gene expression. Deciphering these codes is very challenging due to the large number of variables involved, the non-modular nature of the codes, biases and limitations in current experimental approaches, our limited knowledge in gene expression regulation across the tree of life, and other factors. In recent years, it has been shown that computational modeling and algorithms can significantly accelerate the discovery of novel gene expression codes. Here, we briefly summarize the latest developments and different approaches in the field.

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Research paper thumbnail of Whole cell biophysical modeling of codon-tRNA competition reveals novel insights related to translation dynamics

PLOS Computational Biology

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Research paper thumbnail of High-resolution modeling of the selection on local mRNA folding strength in coding sequences across the tree of life

Genome Biology

Background mRNA can form local secondary structure within the protein-coding sequence, and the st... more Background mRNA can form local secondary structure within the protein-coding sequence, and the strength of this structure is thought to influence gene expression regulation. Previous studies suggest that secondary structure strength may be maintained under selection, but the details of this phenomenon are not well understood. Results We perform a comprehensive study of the selection on local mRNA folding strengths considering variation between species across the tree of life. We show for the first time that local folding strength selection tends to follow a conserved characteristic profile in most phyla, with selection for weak folding at the two ends of the coding region and for strong folding elsewhere in the coding sequence, with an additional peak of selection for strong folding located downstream of the start codon. The strength of this pattern varies between species and organism groups, and we highlight contradicting cases. To better understand the underlying evolutionary proc...

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Research paper thumbnail of Widespread non-modular overlapping codes in the coding regions

Physical Biology

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Research paper thumbnail of Universal evolutionary selection for high dimensional silent patterns of information hidden in the redundancy of viral genetic code

Bioinformatics

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Research paper thumbnail of Networks of ribosome flow models for modeling and analyzing intracellular traffic

Scientific Reports

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Research paper thumbnail of Genome-wide analysis of horizontally acquired genes in the genus Mycobacterium

Scientific Reports

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Research paper thumbnail of Modeling three-dimensional genomic organization in evolution and pathogenesis

Seminars in Cell & Developmental Biology

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Research paper thumbnail of Temporal mRNA Translation Efficiency Is Encoded In Viral Coding Regions 

Science Trends

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Research paper thumbnail of A deterministic mathematical model for bidirectional excluded flow with Langmuir kinetics

PloS one, 2017

In many important cellular processes, including mRNA translation, gene transcription, phosphotran... more In many important cellular processes, including mRNA translation, gene transcription, phosphotransfer, and intracellular transport, biological "particles" move along some kind of "tracks". The motion of these particles can be modeled as a one-dimensional movement along an ordered sequence of sites. The biological particles (e.g., ribosomes or RNAPs) have volume and cannot surpass one another. In some cases, there is a preferred direction of movement along the track, but in general the movement may be bidirectional, and furthermore the particles may attach or detach from various regions along the tracks. We derive a new deterministic mathematical model for such transport phenomena that may be interpreted as a dynamic mean-field approximation of an important model from mechanical statistics called the asymmetric simple exclusion process (ASEP) with Langmuir kinetics. Using tools from the theory of monotone dynamical systems and contraction theory we show that the m...

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Research paper thumbnail of Significant differences in terms of codon usage bias between bacteriophage early and late genes: a comparative genomics analysis

BMC genomics, Jan 13, 2017

Viruses undergo extensive evolutionary selection for efficient replication which effects, among o... more Viruses undergo extensive evolutionary selection for efficient replication which effects, among others, their codon distribution. In the current study, we aimed at understanding the way evolution shapes the codon distribution in early vs. late viral genes in terms of their expression during different stages in the viral replication cycle. To this end we analyzed 14 bacteriophages and 11 human viruses with available information about the expression phases of their genes. We demonstrated evidence of selection for distinct composition of synonymous codons in early and late viral genes in 50% of the analyzed bacteriophages. Among others, this phenomenon may be related to the time specific adaptation of the viral genes to the translation efficiency factors involved at different bacteriophage developmental stages. Specifically, we showed that the differences in codon composition in different temporal gene groups cannot be explained only by phylogenetic proximities between the analyzed bac...

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Research paper thumbnail of Genome scale analysis ofEscherichia coliwith a comprehensive prokaryotic sequence-based biophysical model of translation initiation and elongation

DNA research : an international journal for rapid publication of reports on genes and genomes, Jan 17, 2017

Translation initiation in prokaryotes is affected by the mRNA folding and interaction of the ribo... more Translation initiation in prokaryotes is affected by the mRNA folding and interaction of the ribosome binding site with the ribosomal RNA. The elongation rate is affected, among other factors, by the local biophysical properties of the coding regions, the decoding rates of different codons, and the interactions among ribosomes. Currently, there is no comprehensive biophysical model of translation that enables the prediction of mRNA translation dynamics based only on the transcript sequence and while considering all of these fundamental aspects of translation. In this study, we provide, for the first time, a computational simulative biophysical model of both translation initiation and elongation with all aspects mentioned above. We demonstrate our model performance and advantages focusing on Escherichia coli genes. We further show that the model enables prediction of translation rate, protein levels, and ribosome densities. In addition, our model enables quantifying the effect of sil...

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Research paper thumbnail of A code for transcription elongation speed

RNA biology, Jan 2, 2018

The two major steps of gene expression are transcription and translation. While hundreds of studi... more The two major steps of gene expression are transcription and translation. While hundreds of studies regarding the effect of sequence features on the translation elongation process have been published, very few connect sequence features to the transcription elongation rate. We suggest, for the first time, that short transcript sub-sequences have a typical effect on RNA polymerase (RNAP) speed: we show that nucleotide 5-mers tend to have typical RNAP speed (or transcription rate), which is consistent along different parts of genes and among different groups of genes with high correlation. We also demonstrate that relative RNAP speed correlates with mRNA levels of endogenous and heterologous genes. Furthermore, we show that the estimated transcription and translation elongation rates correlate in endogenous genes. Finally, we demonstrate that our results are consistent for different high resolution experimental measurements of RNAP densities. These results suggest for the first time th...

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Research paper thumbnail of Enhancing heterologous expression in Chlamydomonas reinhardtii by transcript sequence optimization

The Plant journal : for cell and molecular biology, 2018

Various species of microalgae have recently emerged as promising host-organisms for use in biotec... more Various species of microalgae have recently emerged as promising host-organisms for use in biotechnology industries due to their unique properties. These include efficient conversion of sunlight into organic compounds, the ability to grow in extreme conditions and the occurrence of numerous post-translational modification pathways. However, the inability to obtain high levels of nuclear heterologous gene expression in microalgae hinders the development of the entire field. To overcome this limitation, we analyzed different sequence optimization algorithms while studying the effect of transcript sequence features on heterologous expression in the model microalga Chlamydomonas reinhardtii, whose genome consists of rare features such as a high GC content. Based on the analysis of genomic data, we created eight unique sequences coding for a synthetic ferredoxin-hydrogenase enzyme, used here as a reporter gene. Following in silico design, these synthetic genes were transformed into the C...

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Research paper thumbnail of The extent of ribosome queuing in budding yeast

PLoS computational biology, 2018

Ribosome queuing is a fundamental phenomenon suggested to be related to topics such as genome evo... more Ribosome queuing is a fundamental phenomenon suggested to be related to topics such as genome evolution, synthetic biology, gene expression regulation, intracellular biophysics, and more. However, this phenomenon hasn't been quantified yet at a genomic level. Nevertheless, methodologies for studying translation (e.g. ribosome footprints) are usually calibrated to capture only single ribosome protected footprints (mRPFs) and thus limited in their ability to detect ribosome queuing. On the other hand, most of the models in the field assume and analyze a certain level of queuing. Here we present an experimental-computational approach for studying ribosome queuing based on sequencing of RNA footprints extracted from pairs of ribosomes (dRPFs) using a modified ribosome profiling protocol. We combine our approach with traditional ribosome profiling to generate a detailed profile of ribosome traffic. The data are analyzed using computational models of translation dynamics. The approach...

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Research paper thumbnail of Unsupervised detection of regulatory gene expression information in different genomic regions enables gene expression ranking

BMC Bioinformatics

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Research paper thumbnail of Tracking the evolution of 3D gene organization demonstrates its connection to phenotypic divergence

Nucleic Acids Research

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Research paper thumbnail of Widespread signatures of local mRNA folding structure selection in four Dengue virus serotypes

BMC Genomics

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Research paper thumbnail of Evidence of a Direct Evolutionary Selection for Strong Folding and Mutational Robustness Within HIV Coding Regions

Journal of Computational Biology

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Research paper thumbnail of Solving the riddle of the evolution of Shine-Dalgarno based translation in chloroplasts

The chloroplast, a photosynthetic organelle found in all plant and algae species, originates from... more The chloroplast, a photosynthetic organelle found in all plant and algae species, originates from an ancient event in which a cyanobacterium was engulfed by a larger eukaryote. Thus, modern chloroplasts still harbor a bacterial-like genome and carry out all stages of gene expression, including mRNA translation by a 70S ribosome. However, the Shine-Dalgarno model, which predominantly regulates translation initiation by base-pairing between the ribosomal RNA and the mRNA in model bacteria genera, was reported to have ambiguous effects on chloroplast gene expression. Here we show that while the Shine-Dalgarno motif is clearly conserved in proteobacterial mRNAs, its general absence from chloroplast mRNAs is observed in cyanobacteria as well, promoting the idea that the evolutionary process of reducing the centrality of the Shine-Dalgarno mechanism began well before plastid endosymbiosis. As plastid ribosomal RNA anti-Shine-Dalgarno elements are highly similar to their bacterial counterp...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Computational discovery and modeling of novel gene expression rules encoded in the mRNA

Biochemical Society Transactions

The transcript is populated with numerous overlapping codes that regulate all steps of gene expre... more The transcript is populated with numerous overlapping codes that regulate all steps of gene expression. Deciphering these codes is very challenging due to the large number of variables involved, the non-modular nature of the codes, biases and limitations in current experimental approaches, our limited knowledge in gene expression regulation across the tree of life, and other factors. In recent years, it has been shown that computational modeling and algorithms can significantly accelerate the discovery of novel gene expression codes. Here, we briefly summarize the latest developments and different approaches in the field.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Whole cell biophysical modeling of codon-tRNA competition reveals novel insights related to translation dynamics

PLOS Computational Biology

Bookmarks Related papers MentionsView impact

Research paper thumbnail of High-resolution modeling of the selection on local mRNA folding strength in coding sequences across the tree of life

Genome Biology

Background mRNA can form local secondary structure within the protein-coding sequence, and the st... more Background mRNA can form local secondary structure within the protein-coding sequence, and the strength of this structure is thought to influence gene expression regulation. Previous studies suggest that secondary structure strength may be maintained under selection, but the details of this phenomenon are not well understood. Results We perform a comprehensive study of the selection on local mRNA folding strengths considering variation between species across the tree of life. We show for the first time that local folding strength selection tends to follow a conserved characteristic profile in most phyla, with selection for weak folding at the two ends of the coding region and for strong folding elsewhere in the coding sequence, with an additional peak of selection for strong folding located downstream of the start codon. The strength of this pattern varies between species and organism groups, and we highlight contradicting cases. To better understand the underlying evolutionary proc...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Widespread non-modular overlapping codes in the coding regions

Physical Biology

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Universal evolutionary selection for high dimensional silent patterns of information hidden in the redundancy of viral genetic code

Bioinformatics

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Networks of ribosome flow models for modeling and analyzing intracellular traffic

Scientific Reports

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Genome-wide analysis of horizontally acquired genes in the genus Mycobacterium

Scientific Reports

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Modeling three-dimensional genomic organization in evolution and pathogenesis

Seminars in Cell & Developmental Biology

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Temporal mRNA Translation Efficiency Is Encoded In Viral Coding Regions 

Science Trends

Bookmarks Related papers MentionsView impact

Research paper thumbnail of A deterministic mathematical model for bidirectional excluded flow with Langmuir kinetics

PloS one, 2017

In many important cellular processes, including mRNA translation, gene transcription, phosphotran... more In many important cellular processes, including mRNA translation, gene transcription, phosphotransfer, and intracellular transport, biological "particles" move along some kind of "tracks". The motion of these particles can be modeled as a one-dimensional movement along an ordered sequence of sites. The biological particles (e.g., ribosomes or RNAPs) have volume and cannot surpass one another. In some cases, there is a preferred direction of movement along the track, but in general the movement may be bidirectional, and furthermore the particles may attach or detach from various regions along the tracks. We derive a new deterministic mathematical model for such transport phenomena that may be interpreted as a dynamic mean-field approximation of an important model from mechanical statistics called the asymmetric simple exclusion process (ASEP) with Langmuir kinetics. Using tools from the theory of monotone dynamical systems and contraction theory we show that the m...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Significant differences in terms of codon usage bias between bacteriophage early and late genes: a comparative genomics analysis

BMC genomics, Jan 13, 2017

Viruses undergo extensive evolutionary selection for efficient replication which effects, among o... more Viruses undergo extensive evolutionary selection for efficient replication which effects, among others, their codon distribution. In the current study, we aimed at understanding the way evolution shapes the codon distribution in early vs. late viral genes in terms of their expression during different stages in the viral replication cycle. To this end we analyzed 14 bacteriophages and 11 human viruses with available information about the expression phases of their genes. We demonstrated evidence of selection for distinct composition of synonymous codons in early and late viral genes in 50% of the analyzed bacteriophages. Among others, this phenomenon may be related to the time specific adaptation of the viral genes to the translation efficiency factors involved at different bacteriophage developmental stages. Specifically, we showed that the differences in codon composition in different temporal gene groups cannot be explained only by phylogenetic proximities between the analyzed bac...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Genome scale analysis ofEscherichia coliwith a comprehensive prokaryotic sequence-based biophysical model of translation initiation and elongation

DNA research : an international journal for rapid publication of reports on genes and genomes, Jan 17, 2017

Translation initiation in prokaryotes is affected by the mRNA folding and interaction of the ribo... more Translation initiation in prokaryotes is affected by the mRNA folding and interaction of the ribosome binding site with the ribosomal RNA. The elongation rate is affected, among other factors, by the local biophysical properties of the coding regions, the decoding rates of different codons, and the interactions among ribosomes. Currently, there is no comprehensive biophysical model of translation that enables the prediction of mRNA translation dynamics based only on the transcript sequence and while considering all of these fundamental aspects of translation. In this study, we provide, for the first time, a computational simulative biophysical model of both translation initiation and elongation with all aspects mentioned above. We demonstrate our model performance and advantages focusing on Escherichia coli genes. We further show that the model enables prediction of translation rate, protein levels, and ribosome densities. In addition, our model enables quantifying the effect of sil...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of A code for transcription elongation speed

RNA biology, Jan 2, 2018

The two major steps of gene expression are transcription and translation. While hundreds of studi... more The two major steps of gene expression are transcription and translation. While hundreds of studies regarding the effect of sequence features on the translation elongation process have been published, very few connect sequence features to the transcription elongation rate. We suggest, for the first time, that short transcript sub-sequences have a typical effect on RNA polymerase (RNAP) speed: we show that nucleotide 5-mers tend to have typical RNAP speed (or transcription rate), which is consistent along different parts of genes and among different groups of genes with high correlation. We also demonstrate that relative RNAP speed correlates with mRNA levels of endogenous and heterologous genes. Furthermore, we show that the estimated transcription and translation elongation rates correlate in endogenous genes. Finally, we demonstrate that our results are consistent for different high resolution experimental measurements of RNAP densities. These results suggest for the first time th...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Enhancing heterologous expression in Chlamydomonas reinhardtii by transcript sequence optimization

The Plant journal : for cell and molecular biology, 2018

Various species of microalgae have recently emerged as promising host-organisms for use in biotec... more Various species of microalgae have recently emerged as promising host-organisms for use in biotechnology industries due to their unique properties. These include efficient conversion of sunlight into organic compounds, the ability to grow in extreme conditions and the occurrence of numerous post-translational modification pathways. However, the inability to obtain high levels of nuclear heterologous gene expression in microalgae hinders the development of the entire field. To overcome this limitation, we analyzed different sequence optimization algorithms while studying the effect of transcript sequence features on heterologous expression in the model microalga Chlamydomonas reinhardtii, whose genome consists of rare features such as a high GC content. Based on the analysis of genomic data, we created eight unique sequences coding for a synthetic ferredoxin-hydrogenase enzyme, used here as a reporter gene. Following in silico design, these synthetic genes were transformed into the C...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of The extent of ribosome queuing in budding yeast

PLoS computational biology, 2018

Ribosome queuing is a fundamental phenomenon suggested to be related to topics such as genome evo... more Ribosome queuing is a fundamental phenomenon suggested to be related to topics such as genome evolution, synthetic biology, gene expression regulation, intracellular biophysics, and more. However, this phenomenon hasn't been quantified yet at a genomic level. Nevertheless, methodologies for studying translation (e.g. ribosome footprints) are usually calibrated to capture only single ribosome protected footprints (mRPFs) and thus limited in their ability to detect ribosome queuing. On the other hand, most of the models in the field assume and analyze a certain level of queuing. Here we present an experimental-computational approach for studying ribosome queuing based on sequencing of RNA footprints extracted from pairs of ribosomes (dRPFs) using a modified ribosome profiling protocol. We combine our approach with traditional ribosome profiling to generate a detailed profile of ribosome traffic. The data are analyzed using computational models of translation dynamics. The approach...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Unsupervised detection of regulatory gene expression information in different genomic regions enables gene expression ranking

BMC Bioinformatics

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Tracking the evolution of 3D gene organization demonstrates its connection to phenotypic divergence

Nucleic Acids Research

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Widespread signatures of local mRNA folding structure selection in four Dengue virus serotypes

BMC Genomics

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Evidence of a Direct Evolutionary Selection for Strong Folding and Mutational Robustness Within HIV Coding Regions

Journal of Computational Biology

Bookmarks Related papers MentionsView impact