scholarly journals Dynamic evolution of small signaling peptide compensation in plant stem cell control

2022 ◽  
Author(s):  
Choon-Tak Kwon ◽  
Lingli Tang ◽  
Xingang Wang ◽  
Iacopo Gentile ◽  
Anat Hendelman ◽  
...  
Keyword(s):  
Stem Cell ◽  
Allelic Variation ◽  
Phenotypic Diversity ◽  
Genetic Interactions ◽  
Plant Genome ◽  
Single Amino Acid ◽  
Ancestral State ◽  
Single Amino Acid Change ◽  
Short Time ◽  
Solanaceae Family

Gene duplications are a hallmark of plant genome evolution and a foundation for genetic interactions that shape phenotypic diversity. Compensation is a major form of paralog interaction, but how compensation relationships change as allelic variation accumulates is unknown. Here, we leveraged genomics and genome editing across the Solanaceae family to capture the evolution of compensating paralogs. Mutations in the stem cell regulator CLV3 cause floral organs to overproliferate in many plants. In tomato, this phenotype is partially suppressed by transcriptional upregulation of a closely related paralog. Tobacco lost this paralog, resulting in no compensation and extreme clv3 phenotypes. Strikingly, the paralogs of petunia and groundcherry nearly completely suppress clv3, indicating a potent ancestral state of compensation. Cross-species transgenic complementation analyses show this potent compensation partially degenerated in tomato due to a single amino acid change in the paralog and cis-regulatory variation that limits its transcriptional upregulation. Our findings show how genetic interactions are remodeled following duplications, and suggest that dynamic paralog evolution is widespread over short time scales and impacts phenotypic variation from natural and engineered mutations.

scholarly journals Cryptic genetic variation in a heat shock protein modifies the outcome of a mutation affecting epidermal stem cell development in C. elegans

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sneha L. Koneru ◽  
Mark Hintze ◽  
Dimitris Katsanos ◽  
Michalis Barkoulas
Keyword(s):  
Genetic Variation ◽  
Stem Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Fate ◽  
Cell Development ◽  
Wnt Signalling ◽  
Single Amino Acid ◽  
Cryptic Genetic Variation ◽  
Seam Cell

AbstractA fundamental question in medical genetics is how the genetic background modifies the phenotypic outcome of mutations. We address this question by focusing on the seam cells, which display stem cell properties in the epidermis of Caenorhabditis elegans. We demonstrate that a putative null mutation in the GATA transcription factor egl-18, which is involved in seam cell fate maintenance, is more tolerated in the CB4856 isolate from Hawaii than the lab reference strain N2 from Bristol. We identify multiple quantitative trait loci (QTLs) underlying the difference in phenotype expressivity between the two isolates. These QTLs reveal cryptic genetic variation that reinforces seam cell fate through potentiating Wnt signalling. Within one QTL region, a single amino acid deletion in the heat shock protein HSP-110 in CB4856 is sufficient to modify Wnt signalling and seam cell development, highlighting that natural variation in conserved heat shock proteins can shape phenotype expressivity.

scholarly journals Single amino acid changes in the mumps virus haemagglutinin–neuraminidase and polymerase proteins are associated with neuroattenuation

2009 ◽  
Vol 90 (7) ◽  
pp. 1741-1747 ◽  
Author(s):  
Tahir H. Malik ◽  
Candie Wolbert ◽  
Laura Nerret ◽  
Christian Sauder ◽  
Steven Rubin
Keyword(s):  
Amino Acid ◽  
Clinical Isolate ◽  
Amino Acid Change ◽  
Mumps Virus ◽  
Site Directed Mutagenesis ◽  
Single Amino Acid ◽  
Supporting Evidence ◽  
L Protein ◽  
Single Amino Acid Change

It has previously been shown that three amino acid changes, one each in the fusion (F; Ala/Thr-91→Thr), haemagglutinin–neuraminidase (HN; Ser-466→Asn) and polymerase (L; Ile-736→Val) proteins, are associated with attenuation of a neurovirulent clinical isolate of mumps virus (88-1961) following serial passage in vitro. Here, using full-length cDNA plasmid clones and site-directed mutagenesis, it was shown that the single amino acid change in the HN protein and to a lesser extent, the change in the L protein, resulted in neuroattenuation, as assessed in rats. The combination of both amino acid changes caused neuroattenuation of the virus to levels previously reported for the clinical isolate following attenuation in vitro. The amino acid change in the F protein, despite having a dramatic effect on protein function in vitro, was previously shown to not be involved in the observed neuroattenuation, highlighting the importance of conducting confirmatory in vivo studies. This report provides additional supporting evidence for the role of the HN protein as a virulence factor and, as far as is known, is the first report to associate an amino acid change in the L protein with mumps virus neuroattenuation.

Genetic Analysis of Caenorhabditis elegans glp-1 Mutants Suggests Receptor Interaction or Competition

Genetics ◽  
2003 ◽  
Vol 163 (1) ◽  
pp. 115-132 ◽  
Author(s):  
Anita S-R Pepper ◽  
Darrell J Killian ◽  
E Jane Albert Hubbard
Keyword(s):  
Transmembrane Domain ◽  
Limiting Factors ◽  
Single Amino Acid ◽  
Receptor Interaction ◽  
Gain Of Function ◽  
Ligand Interaction ◽  
Receptor Proteins ◽  
C Elegans ◽  
Single Amino Acid Change ◽  
Functional Defect

Abstract glp-1 encodes a member of the highly conserved LIN-12/Notch family of receptors that mediates the mitosis/meiosis decision in the C. elegans germline. We have characterized three mutations that represent a new genetic and phenotypic class of glp-1 mutants, glp-1(Pro). The glp-1(Pro) mutants display gain-of-function germline pattern defects, most notably a proximal proliferation (Pro) phenotype. Each of three glp-1(Pro) alleles encodes a single amino acid change in the extracellular part of the receptor: two in the LIN-12/Notch repeats (LNRs) and one between the LNRs and the transmembrane domain. Unlike other previously described gain-of-function mutations that affect this region of LIN-12/Notch family receptors, the genetic behavior of glp-1(Pro) alleles is not consistent with simple hypermorphic activity. Instead, the mutant phenotype is suppressed by wild-type doses of glp-1. Moreover, a trans-heterozygous combination of two highly penetrant glp-1(Pro) mutations is mutually suppressing. These results lend support to a model for a higher-order receptor complex and/or competition among receptor proteins for limiting factors that are required for proper regulation of receptor activity. Double-mutant analysis with suppressors and enhancers of lin-12 and glp-1 further suggests that the functional defect in glp-1(Pro) mutants occurs prior to or at the level of ligand interaction.

A single amino acid change makes a rat neuronal sodium channel highly sensitive to pyrethroid insecticides

FEBS Letters ◽  
2000 ◽  
Vol 470 (2) ◽  
pp. 135-138 ◽  
Author(s):  
H. Vais ◽  
S. Atkinson ◽  
N. Eldursi ◽  
A.L. Devonshire ◽  
M.S. Williamson ◽  
...  
Keyword(s):  
Amino Acid ◽  
Sodium Channel ◽  
Amino Acid Change ◽  
Single Amino Acid ◽  
Pyrethroid Insecticides ◽  
Highly Sensitive ◽  
Single Amino Acid Change

scholarly journals Enhancement of the Efficiency of Secretion of Heterologous Lipase in Escherichia coli by Directed Evolution of the ABC Transporter System

2005 ◽  
Vol 71 (7) ◽  
pp. 3468-3474 ◽  
Author(s):  
Gyeong Tae Eom ◽  
Jae Kwang Song ◽  
Jung Hoon Ahn ◽  
Yeon Soo Seo ◽  
Joon Shick Rhee
Keyword(s):  
Escherichia Coli ◽  
Directed Evolution ◽  
Abc Transporter ◽  
Microtiter Plate ◽  
Single Amino Acid ◽  
Wild Type ◽  
E Coli ◽  
Single Amino Acid Change ◽  
Secretion Efficiency

ABSTRACT The ABC transporter (TliDEF) from Pseudomonas fluorescens SIK W1, which mediated the secretion of a thermostable lipase (TliA) into the extracellular space in Escherichia coli, was engineered using directed evolution (error-prone PCR) to improve its secretion efficiency. TliD mutants with increased secretion efficiency were identified by coexpressing the mutated tliD library with the wild-type tliA lipase in E. coli and by screening the library with a tributyrin-emulsified indicator plate assay and a microtiter plate-based assay. Four selected mutants from one round of error-prone PCR mutagenesis, T6, T8, T24, and T35, showed 3.2-, 2.6-, 2.9-, and 3.0-fold increases in the level of secretion of TliA lipase, respectively, but had almost the same level of expression of TliD in the membrane as the strain with the wild-type TliDEF transporter. These results indicated that the improved secretion of TliA lipase was mediated by the transporter mutations. Each mutant had a single amino acid change in the predicted cytoplasmic regions in the membrane domain of TliD, implying that the corresponding region of TliD was important for the improved and successful secretion of the target protein. We therefore concluded that the efficiency of secretion of a heterologous protein in E. coli can be enhanced by in vitro engineering of the ABC transporter.

Further characterization and determination of the single amino acid change in thetsI138reovirus thermosensitive mutant

2012 ◽  
Vol 58 (5) ◽  
pp. 589-595
Author(s):  
Guy Lemay ◽  
Martin Bisaillon
Keyword(s):  
Amino Acid ◽  
Amino Acid Change ◽  
Genetic Alterations ◽  
Biological Properties ◽  
Single Amino Acid ◽  
Temperature Sensitive ◽  
Nonpermissive Temperature ◽  
Gene Encoding ◽  
Viral Particles ◽  
Single Amino Acid Change

Many temperature-sensitive mutants have been isolated in early studies of mammalian reovirus. However, the biological properties and nature of the genetic alterations remain incompletely explored for most of these mutants. The mutation harbored by the tsI138 mutant was already assigned to the L3 gene encoding the λ1 protein. In the present study, this mutant was further studied as a possible tool to establish the role of the putative λ1 enzymatic activities in viral multiplication. It was observed that synthesis of viral proteins is only marginally reduced, while it was difficult to recover viral particles at the nonpermissive temperature. A single nucleotide substitution resulting in an amino acid change was found; the position of this amino acid is consistent with a probable defect in assembly of the inner capsid at the nonpermissive temperature.

scholarly journals The Spike Protein VP4 Defines the Endocytic Pathway Used by Rotavirus To Enter MA104 Cells

2012 ◽  
Vol 87 (3) ◽  
pp. 1658-1663 ◽  
Author(s):  
Marco A. Díaz-Salinas ◽  
Pedro Romero ◽  
Rafaela Espinosa ◽  
Yasutaka Hoshino ◽  
Susana López ◽  
...  
Keyword(s):  
Surface Protein ◽  
Endocytic Pathway ◽  
Spike Protein ◽  
Single Amino Acid ◽  
Cellular Receptors ◽  
Hypertonic Medium ◽  
Bovine Rotavirus ◽  
Single Amino Acid Change ◽  
Interfering Rna

ABSTRACTRotaviruses are internalized into MA104 cells by endocytosis, with different endocytic pathways used depending on the virus strain. The bovine rotavirus UK strain enters cells through a clathrin-mediated endocytic process, while the simian rhesus rotavirus (RRV) strain uses a poorly defined endocytic pathway that is clathrin and caveolin independent. The viral surface protein VP7 and the spike protein VP4 interact with cellular receptors during cell binding and penetration. To determine the viral protein that defines the mechanism of internalization, we used a panel of UK × RRV reassortant viruses having different combinations of the viral structural proteins. Characterization of the infectivities of these reassortants in MA104 cells either transfected with a small interfering RNA (siRNA) against the heavy chain of clathrin or incubated with hypertonic medium that destabilizes the clathrin coat clearly showed that VP4 determines the pathway of virus entry. Of interest, the characterization of Nar3, a sialic acid-independent variant of RRV, showed that a single amino acid change in VP4 shifts the route of entry from being clathrin dependent to clathrin independent. Furthermore, characterizations of several additional rotavirus strains that differ in their use of cellular receptors showed that all entered cells by clathrin-mediated endocytosis, suggesting that diverse VP4-cell surface interactions can lead to rotavirus cell entry through this endocytic pathway.

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