Faculty Opinions recommendation of A genome-wide screen for regulators of TORC1 in response to amino acid starvation reveals a conserved Npr2/3 complex.

Abstract Carrot is a major source of provitamin A in a human diet. Two of the most important traits for carrot breeding are carotenoid contents and root color. To examine genomic regions related to these traits and develop DNA markers for carrot breeding, we performed a genome-wide association study (GWAS) using genome-wide single-nucleotide polymorphisms (SNPs) in two F2 populations, both derived from crosses of orange root carrots bred by a Japanese seed company. The GWAS revealed 21 significant associations, and the physical position of some associations suggested two possible candidate genes. An Orange (Or) gene was a possible candidate for visual color evaluation and the α- and β-carotene contents. Sanger sequencing detected a new allele of Or with an SNP which caused a non-synonymous amino acid substitution. Genotypes of this SNP corresponded to the visual evaluation of root color in another breeding line. A chromoplast-specific lycopene β-cyclase (CYC-B) gene was a possible candidate for the β/α carotene ratio. On CYC-B, five amino acid substitutions were detected between parental plants of the F2 population. The detected associations and SNPs on the possible candidate genes will contribute to carrot breeding and the understanding of carotenoid biosynthesis and accumulation in orange carrots.

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Genome wide association study of HTLV-1–associated myelopathy/tropical spastic paraparesis in the Japanese population

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2004199118 ◽

2021 ◽

Vol 118 (11) ◽

pp. e2004199118

Author(s):

Marina Penova ◽

Shuji Kawaguchi ◽

Jun-ichirou Yasunaga ◽

Takahisa Kawaguchi ◽

Tomoo Sato ◽

...

Keyword(s):

Amino Acid ◽

Association Study ◽

Proviral Load ◽

Odds Ratio ◽

Japanese Population ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Genome Wide ◽

A Genome ◽

Increased Risk

HTLV-1–associated myelopathy (HAM/TSP) is a chronic and progressive inflammatory disease of the central nervous system. The aim of our study was to identify genetic determinants related to the onset of HAM/TSP in the Japanese population. We conducted a genome-wide association study comprising 753 HAM/TSP patients and 899 asymptomatic HTLV-1 carriers. We also performed comprehensive genotyping of HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1 genes using next-generation sequencing technology for 651 HAM/TSP patients and 804 carriers. A strong association was observed in HLA class I (P = 1.54 × 10−9) and class II (P = 1.21 × 10−8) loci with HAM/TSP. Association analysis using HLA genotyping results showed that HLA-C*07:02 (P = 2.61 × 10−5), HLA-B*07:02 (P = 4.97 × 10−10), HLA-DRB1*01:01 (P = 1.15 × 10−9) and HLA-DQB1*05:01 (P = 2.30 × 10−9) were associated with disease risk, while HLA-B*40:06 (P = 3.03 × 10−5), HLA-DRB1*15:01 (P = 1.06 × 10−5) and HLA-DQB1*06:02 (P = 1.78 × 10−6) worked protectively. Logistic regression analysis identified amino acid position 7 in the G-BETA domain of HLA-DRB1 as strongly associated with HAM/TSP (P = 9.52 × 10−10); individuals homozygous for leucine had an associated increased risk of HAM/TSP (odds ratio, 9.57), and proline was protective (odds ratio, 0.65). Both associations were independent of the known risk associated with proviral load. DRB1-GB-7-Leu was not significantly associated with proviral load. We have identified DRB1-GB-7-Leu as a genetic risk factor for HAM/TSP development independent of proviral load. This suggests that the amino acid residue may serve as a specific marker to identify the risk of HAM/TSP even without knowledge of proviral load. In light of its allele frequency worldwide, this biomarker will likely prove useful in HTLV-1 endemic areas across the globe.

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Evolutionary switches between two serine codon sets are driven by selection

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1615832113 ◽

2016 ◽

Vol 113 (46) ◽

pp. 13109-13113 ◽

Cited By ~ 16

Author(s):

Igor B. Rogozin ◽

Frida Belinky ◽

Vladimir Pavlenko ◽

Svetlana A. Shabalina ◽

David M. Kristensen ◽

...

Keyword(s):

Amino Acid ◽

Great Majority ◽

Purifying Selection ◽

Nucleotide Substitutions ◽

Closely Related Species ◽

Published Evidence ◽

Genome Wide ◽

A Genome ◽

Evolutionarily Conserved ◽

Frequent Reversal

Serine is the only amino acid that is encoded by two disjoint codon sets so that a tandem substitution of two nucleotides is required to switch between the two sets. Previously published evidence suggests that, for the most evolutionarily conserved serines, the codon set switch occurs by simultaneous substitution of two nucleotides. Here we report a genome-wide reconstruction of the evolution of serine codons in triplets of closely related species from diverse prokaryotes and eukaryotes. The results indicate that the great majority of codon set switches proceed by two consecutive nucleotide substitutions, via a threonine or cysteine intermediate, and are driven by selection. These findings imply a strong pressure of purifying selection in protein evolution, which in the case of serine codon set switches occurs via an initial deleterious substitution quickly followed by a second, compensatory substitution. The result is frequent reversal of amino acid replacements and, at short evolutionary distances, pervasive homoplasy.

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Genome-wide siRNA screen reveals amino acid starvation-induced autophagy requires SCOC and WAC

The EMBO Journal ◽

10.1038/emboj.2012.36 ◽

2012 ◽

Vol 31 (8) ◽

pp. 1931-1946 ◽

Cited By ~ 73

Author(s):

Nicole C McKnight ◽

Harold B J Jefferies ◽

Endalkachew A Alemu ◽

Rebecca E Saunders ◽

Michael Howell ◽

...

Keyword(s):

Amino Acid ◽

Amino Acid Starvation ◽

Sirna Screen ◽

Genome Wide

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Comprehensive Genome-Wide Identification and Transcript Profiling of GABA Pathway Gene Family in Apple (Malus domestica)

Genes ◽

10.3390/genes12121973 ◽

2021 ◽

Vol 12 (12) ◽

pp. 1973

Author(s):

Qingbo Zheng ◽

Shenghui Su ◽

Zhe Wang ◽

Yongzhang Wang ◽

Xiaozhao Xu

Keyword(s):

Amino Acid ◽

Gene Family ◽

Alternative Pathway ◽

Functional Characterization ◽

Gaba Shunt ◽

Gaba Transporters ◽

Pathway Gene ◽

Genome Wide ◽

A Genome

γ-Aminobutyric Acid (GABA), a four-carbon non-protein amino acid, is a significant component of the free amino acid pool in most prokaryotic and eukaryotic organisms. GABA is involved in pH regulation, maintaining C/N balance, plant development and defence, as well as a compatible osmolyte and an alternative pathway for glutamate utilization via anion flux. Glutamate decarboxylase (GAD, EC 4.1.1.15) and GABA transaminase (GABA-T, EC 2.6.1.19) are two key enzymes involved in the synthesis and metabolism of GABA. Recently, GABA transporters (GATs), protein and aluminium-activated malate transporter (ALMT) proteins which function as GABA receptors, have been shown to be involved in GABA regulation. However, there is no report on the characterization of apple GABA pathway genes. In this study, we performed a genome-wide analysis and expression profiling of the GABA pathway gene family in the apple genome. A total of 24 genes were identified including five GAD genes (namely MdGAD 1–5), two GABA-T genes (namely MdGABA-T 1,2), 10 GAT genes (namely GAT 1–10) and seven ALMT genes (namely MdALMT1–7). These genes were randomly distributed on 12 chromosomes. Phylogenetic analyses grouped GABA shunt genes into three clusters—cluster I, cluster II, and cluster III—which had three, four, and five genes, respectively. The expression profile analysis revealed significant MdGAD4 expression levels in both fruit and flower organs, except pollen. However, there were no significant differences in the expression of other GABA shunt genes in different tissues. This work provides the first characterization of the GABA shunt gene family in apple and suggests their importance in apple response to abiotic stress. These results can serve as a guide for future studies on the understanding and functional characterization of these gene families.

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Complementary α-arrestin - Rsp5 ubiquitin ligase complexes control selective nutrient transporter endocytosis in response to amino acid availability

10.1101/2020.04.24.059832 ◽

2020 ◽

Author(s):

Vasyl Ivashov ◽

Johannes Zimmer ◽

Sinead Schwabl ◽

Jennifer Kahlhofer ◽

Sabine Weys ◽

...

Keyword(s):

Amino Acid ◽

Ubiquitin Ligase ◽

Amino Acid Transporters ◽

General Amino Acid Control ◽

Amino Acid Availability ◽

Acid Control ◽

Genome Wide ◽

A Genome ◽

Lysine Residues ◽

Nutrient Transporter

AbstractHow cells adjust transport across their membranes is incompletely understood. Previously, we have shown that S.cerevisiae broadly re-configures the nutrient transporters at the plasma membrane in response to amino acid availability, through selective endocytosis of sugar- and amino acid transporters (AATs) (Müller et al., 2015). A genome-wide screen now revealed that Art2/Ecm21, a member of the α-arrestin family of Rsp5 ubiquitin ligase adaptors, is required for the simultaneous endocytosis of four AATs and induced during starvation by the general amino acid control pathway. Art2 uses a basic patch to recognize C-terminal acidic sorting motifs in these AATs and instructs Rsp5 to ubiquitinate proximal lysine residues. In response to amino acid excess, Rsp5 instead uses TORC1-activated Art1 to detect N-terminal acidic sorting motifs within the same AATs, which initiates exclusive substrate-induced endocytosis of individual AATs. Thus, amino acid availability activates complementary α-arrestin-Rsp5-complexes to control selective endocytosis for nutrient acquisition.

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Complementary α-arrestin-ubiquitin ligase complexes control nutrient transporter endocytosis in response to amino acids

eLife ◽

10.7554/elife.58246 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 2

Author(s):

Vasyl Ivashov ◽

Johannes Zimmer ◽

Sinead Schwabl ◽

Jennifer Kahlhofer ◽

Sabine Weys ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Ubiquitin Ligase ◽

Amino Acid Transporters ◽

General Amino Acid Control ◽

Amino Acid Availability ◽

Genome Wide ◽

A Genome ◽

Lysine Residues ◽

Nutrient Transporter

How cells adjust nutrient transport across their membranes is incompletely understood. Previously, we have shown that S. cerevisiae broadly re-configures the nutrient transporters at the plasma membrane in response to amino acid availability, through endocytosis of sugar- and amino acid transporters (AATs) (Müller et al., 2015). A genome-wide screen now revealed that the selective endocytosis of four AATs during starvation required the α-arrestin family protein Art2/Ecm21, an adaptor for the ubiquitin ligase Rsp5, and its induction through the general amino acid control pathway. Art2 uses a basic patch to recognize C-terminal acidic sorting motifs in AATs and thereby instructs Rsp5 to ubiquitinate proximal lysine residues. When amino acids are in excess, Rsp5 instead uses TORC1-activated Art1 to detect N-terminal acidic sorting motifs within the same AATs, which initiates exclusive substrate-induced endocytosis. Thus, amino acid excess or starvation activate complementary α-arrestin-Rsp5-complexes to control selective endocytosis and adapt nutrient acquisition.

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Chlorophenol stress affects aromatic amino acid biosynthesis-a genome-wide study

Yeast ◽

10.1002/yea.1825 ◽

2010 ◽

Vol 28 (1) ◽

pp. 81-91 ◽

Cited By ~ 7

Author(s):

Vikas Yadav ◽

Kirti Shitiz ◽

Rishi Pandey ◽

Jyoti Yadav

Keyword(s):

Amino Acid ◽

Aromatic Amino Acid ◽

Amino Acid Biosynthesis ◽

Acid Biosynthesis ◽

Aromatic Amino Acid Biosynthesis ◽

Genome Wide ◽

A Genome ◽

Genome Wide Study

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Extensive translation of small ORFs revealed by polysomal ribo-Seq

10.1101/002998 ◽

2014 ◽

Cited By ~ 1

Author(s):

Julie L Aspden ◽

Ying Chen Eyre-Walker ◽

Rose J. Phillips ◽

Michele Brocard ◽

Unum Amin ◽

...

Keyword(s):

Amino Acid ◽

Species Conservation ◽

Open Reading Frames ◽

Sequence Specificity ◽

Small Peptides ◽

Genome Wide ◽

A Genome ◽

Evolutionary Features ◽

Amino Acid Signature ◽

Small Orfs

Thousands of small Open Reading Frames (smORFs) encoding small peptides of fewer than 100 amino acids exist in our genomes. Examples of functional smORFs have been characterised in a few species but the actual number of translated smORFs, and their molecular, functional and evolutionary features are not known. Here we present a genome-wide assessment of smORF translation by ribosomal profiling of polysomal fractions. This polysomal ribo-Seq suggests that smORFs are translated at the same level and in the same relative numbers (80%) as normal proteins. The smORF peptides appear widely conserved, show activity in cells, and display a putative amino acid signature. These findings reinforce the idea that smORFs are an abundant and fundamental genome component, displaying features usually attributed to canonical proteins, including high translation levels, biological function, amino acid sequence specificity and cross-species conservation.

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