scholarly journals Signatures of optimal codon usage in metabolic genes inform budding yeast ecology

PLoS Biology ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. e3001185
Author(s):  
Abigail Leavitt LaBella ◽  
Dana A. Opulente ◽  
Jacob L. Steenwyk ◽  
Chris Todd Hittinger ◽  
Antonis Rokas
Keyword(s):  
Codon Usage ◽  
Codon Optimization ◽  
Kluyveromyces Lactis ◽  
Nutrient Sensing ◽  
Genomic Variation ◽  
Ecological Niches ◽  
Galactose Metabolism ◽  
Optimal Codon ◽  
High Gene Expression ◽  
High Gene

Reverse ecology is the inference of ecological information from patterns of genomic variation. One rich, heretofore underutilized, source of ecologically relevant genomic information is codon optimality or adaptation. Bias toward codons that match the tRNA pool is robustly associated with high gene expression in diverse organisms, suggesting that codon optimization could be used in a reverse ecology framework to identify highly expressed, ecologically relevant genes. To test this hypothesis, we examined the relationship between optimal codon usage in the classic galactose metabolism (GAL) pathway and known ecological niches for 329 species of budding yeasts, a diverse subphylum of fungi. We find that optimal codon usage in the GAL pathway is positively correlated with quantitative growth on galactose, suggesting that GAL codon optimization reflects increased capacity to grow on galactose. Optimal codon usage in the GAL pathway is also positively correlated with human-associated ecological niches in yeasts of the CUG-Ser1 clade and with dairy-associated ecological niches in the family Saccharomycetaceae. For example, optimal codon usage of GAL genes is greater than 85% of all genes in the genome of the major human pathogen Candida albicans (CUG-Ser1 clade) and greater than 75% of genes in the genome of the dairy yeast Kluyveromyces lactis (family Saccharomycetaceae). We further find a correlation between optimization in the GALactose pathway genes and several genes associated with nutrient sensing and metabolism. This work suggests that codon optimization harbors information about the metabolic ecology of microbial eukaryotes. This information may be particularly useful for studying fungal dark matter—species that have yet to be cultured in the lab or have only been identified by genomic material.

scholarly journals Signatures of optimal codon usage predict metabolic ecology in budding yeasts

2020 ◽  
Author(s):  
Abigail Leavitt LaBella ◽  
Dana A. Opulente ◽  
Jacob Steenwyk ◽  
Chris Todd Hittinger ◽  
Antonis Rokas
Keyword(s):  
Codon Usage ◽  
Codon Optimization ◽  
Kluyveromyces Lactis ◽  
Genomic Variation ◽  
Ecological Niches ◽  
Galactose Metabolism ◽  
Optimal Codon ◽  
High Gene Expression ◽  
Metabolic Ecology ◽  
Thiamine Biosynthesis

ABSTRACTReverse ecology is the inference of ecological information from patterns of genomic variation. One rich, heretofore underutilized, source of ecologically-relevant genomic information is codon optimality or adaptation. Bias toward codons that match the tRNA pool is robustly associated with high gene expression in diverse organisms, suggesting that codon optimization could be used in a reverse ecology framework to identify highly expressed, ecologically relevant genes. To test this hypothesis, we examined the relationship between optimal codon usage in the classic galactose metabolism (GAL) pathway and known ecological niches for 329 species of budding yeasts, a diverse subphylum of fungi. We find that optimal codon usage in the GAL pathway is positively correlated with quantitative growth on galactose, suggesting that GAL codon optimization reflects increased capacity to grow on galactose. Optimal codon usage in the GAL pathway is also positively correlated with human-associated ecological niches in yeasts of the CUG-Ser1 clade and with dairy-associated ecological niches in the family Saccharomycetaceae. For example, optimal codon usage of GAL genes is greater than 85% of all genes in the major human pathogen Candida albicans (CUG-Ser1 clade) and greater than 75% of genes in the dairy yeast Kluyveromyces lactis (family Saccharomycetaceae). We further find a correlation between optimization in the thiamine biosynthesis and GAL pathways. As a result, optimal codon usage in thiamine biosynthesis genes is also associated with dairy ecological niches in Saccharomycetaceae, which may reflect competition with co-occurring microbes for extracellular thiamine. This work highlights the potential of codon optimization as a tool for gaining insights into the metabolic ecology of microbial eukaryotes. Doing so may be especially illuminating for studying fungal dark matter—species that have yet to be cultured in the lab or have only been identified by genomic material.

scholarly journals Retained Heterodisomy Is Associated with High Gene Expression in Hyperhaploid Inflammatory Leiomyosarcoma

Neoplasia ◽  
2012 ◽  
Vol 14 (9) ◽  
pp. 807-IN5 ◽  
Author(s):  
Karolin H. Nord ◽  
Kajsa Paulsson ◽  
Srinivas Veerla ◽  
Johan Wejde ◽  
Otte Brosjö ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Gene Expression ◽  
High Gene

scholarly journals Interaction between transcriptional activator protein LAC9 and negative regulatory protein GAL80.

1989 ◽  
Vol 9 (7) ◽  
pp. 2950-2956 ◽  
Author(s):  
J M Salmeron ◽  
S D Langdon ◽  
S A Johnston
Keyword(s):  
Transcriptional Activation ◽  
Kluyveromyces Lactis ◽  
Regulatory Protein ◽  
Wild Type ◽  
Galactose Metabolism ◽  
Metabolism Regulation ◽  
Transcriptional Activator Protein ◽  
The Difference ◽  
Carboxy Terminal

In Saccharomyces cerevisiae, transcriptional activation mediated by the GAL4 regulatory protein is repressed in the absence of galactose by the binding of the GAL80 protein, an interaction that requires the carboxy-terminal 28 amino acids of GAL4. The homolog of GAL4 from Kluyveromyces lactis, LAC9, activates transcription in S. cerevisiae and is highly similar to GAL4 in its carboxyl terminus but is not repressed by wild-type levels of GAL80 protein. Here we show that GAL80 does repress LAC9-activated transcription in S. cerevisiae if overproduced. We sought to determine the molecular basis for the difference in the responses of the LAC9 and GAL4 proteins to GAL80. Our results indicate that this difference is due primarily to the fact that under wild-type conditions, the level of LAC9 protein in S. cerevisiae is much higher than that of GAL4, which suggests that LAC9 escapes GAL80-mediated repression by titration of GAL80 protein in vivo. The difference in response to GAL80 is not due to amino acid sequence differences between the LAC9 and GAL4 carboxyl termini. We discuss the implications of these results for the mechanism of galactose metabolism regulation in S. cerevisiae and K. lactis.

scholarly journals Muscle overexpression of Klf15 via an AAV8-Spc5-12 construct does not provide benefits in spinal muscular atrophy mice

Gene Therapy ◽  
2020 ◽  
Vol 27 (10-11) ◽  
pp. 505-515
Author(s):  
Nina Ahlskog ◽  
Daniel Hayler ◽  
Anja Krueger ◽  
Sabrina Kubinski ◽  
Peter Claus ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Treatment Options ◽  
Survival Motor Neuron ◽  
Significant Activity ◽  
Dependent Manner ◽  
Patient Response ◽  
High Gene Expression ◽  
Virus Serotype ◽  
High Gene

AbstractSpinal muscular atrophy (SMA) is a neuromuscular disease caused by loss of the survival motor neuron (SMN) gene. While there are currently two approved gene-based therapies for SMA, availability, high cost, and differences in patient response indicate that alternative treatment options are needed. Optimal therapeutic strategies will likely be a combination of SMN-dependent and -independent treatments aimed at alleviating symptoms in the central nervous system and peripheral muscles. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates key metabolic and ergogenic pathways in muscle. We have recently reported significant downregulation of Klf15 in muscle of presymptomatic SMA mice. Importantly, perinatal upregulation of Klf15 via transgenic and pharmacological methods resulted in improved disease phenotypes in SMA mice, including weight and survival. In the current study, we designed an adeno-associated virus serotype 8 (AAV8) vector to overexpress a codon-optimized Klf15 cDNA under the muscle-specific Spc5-12 promoter (AAV8-Klf15). Administration of AAV8-Klf15 to severe Taiwanese Smn−/−;SMN2 or intermediate Smn2B/− SMA mice significantly increased Klf15 expression in muscle. We also observed significant activity of the AAV8-Klf15 vector in liver and heart. AAV8-mediated Klf15 overexpression moderately improved survival in the Smn2B/− model but not in the Taiwanese mice. An inability to specifically induce Klf15 expression at physiological levels in a time- and tissue-dependent manner may have contributed to this limited efficacy. Thus, our work demonstrates that an AAV8-Spc5-12 vector induces high gene expression as early as P2 in several tissues including muscle, heart, and liver, but highlights the challenges of achieving meaningful vector-mediated transgene expression of Klf15.

scholarly journals Non-optimal codon usage affects expression, structure and function of clock protein FRQ

Nature ◽  
2013 ◽  
Vol 495 (7439) ◽  
pp. 111-115 ◽  
Author(s):  
Mian Zhou ◽  
Jinhu Guo ◽  
Joonseok Cha ◽  
Michael Chae ◽  
She Chen ◽  
...  
Keyword(s):  
Codon Usage ◽  
Structure And Function ◽  
Optimal Codon ◽  
And Function ◽  
Clock Protein
Sign in / Sign up

Export Citation Format

Share Document