scholarly journals Deep Conservation of Hid-Like RHG Gene Family Homologs in Winged Insects Revealed by “Taxon Hopping” BLAST

Insects ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 957
Author(s):  
Markus Friedrich
Keyword(s):  
Cell Death ◽  
Gene Family ◽  
Acyrthosiphon Pisum ◽  
Amino Acid Residues ◽  
Exceptional Sequence ◽  
Death Studies ◽  
Splicing Pattern ◽  
The Family ◽  
Splice Isoform ◽  
Genome Model

Together with sickle (skl), the Drosophila paralogs reaper (rpr), head involution defective (hid), and grim (RHG) control a critical switch in the induction of programmed cell death. RHG homologs have been identified in other dipteran and lepidopteran species but not beyond. Revisiting this issue with a “taxon hopping” BLAST search strategy in current genome and transcriptome resources, I detected high confidence RHG homologs in Coleoptera, Hymenoptera, Hemiptera, and Dictyoptera. Analyses of gene structure and protein sequence conservation revealed aconserved splicing pattern and highly conserved amino acid residues at both the N- and C-terminal ends that identify hid as the most ancestrally organized RHG gene family member in Drosophila. hid-like RHG homologs were also detected in mosquitoes, redefining their michelob_x (mx) genes as an expansion of derived RHG homologs. Only singleton homologs were detected in the large majority of other insect clades. Lepidopteran RHG homologs, however, stand out by producing an evolutionarily-derived splice isoform, identified in previous work, in addition to the newly detected hid-like isoform. Exceptional sequence diversification of select RHG homologs at the family- and genus-level explain their previous elusiveness in important insect genome model species like the red flour beetle Tribolium castaneum and the pea aphid Acyrthosiphon pisum. Combined, these findings expand the minimal age of the RHG gene family by about 100 million years and open new avenues for molecular cell death studies in insects.

scholarly journals Deep conservation of Hid-like RHG gene family homologs in winged insects

2021 ◽  
Author(s):  
Markus Friedrich
Keyword(s):  
Cell Death ◽  
Gene Family ◽  
Acyrthosiphon Pisum ◽  
Amino Acid Residues ◽  
Exceptional Sequence ◽  
Death Studies ◽  
Splicing Pattern ◽  
The Family ◽  
Splice Isoform ◽  
Genome Model

ABSTRACTTogether with sickle (skl), the Drosophila paralogs reaper (rpr), head involution defective (hid), and grim (RHG) control a critical switch in the induction of programmed cell death. RHG homologs have been identified in other dipteran and lepidopteran species but not beyond. Revisiting this issue with a “taxon hopping” BLAST search strategy in current genome and transcriptome resources, I detected high confidence RHG homologs in Coleoptera (beetles), Hymenoptera (bees+wasps), Hemiptera (true bugs), termites, and cockroaches. Analyses of gene structure and protein sequence conservation revealed a shared ancestral splicing pattern and highly conserved amino acid residues at both the N- and C-terminal ends that identify hid as the most ancestrally organized RHG gene family member in Drosophila. hid-like RHG homologs were also detected in mosquitoes, redefining their michelob_x (mx) genes as an expansion of derived RHG homologs. Only singleton homologs were detected in the large majority of other insect clades. Lepidopteran RHG homologs, however, stand out by producing an evolutionarily derived splice isoform, identified in previous work, in addition to the newly detected hid-like isoform. Exceptional sequence diversification of select RHG homologs at the family- and genus-level explain their elusiveness in important insect genome model species like the red flour beetle Tribolium castaneum and the pea aphid Acyrthosiphon pisum. Combined, these findings expand the minimal age of the RHG gene family by about 100 million years and open new avenues for molecular cell death studies in insects.

scholarly journals Frequent amplification of HDAC genes and efficacy of HDAC inhibitor chidamide and PD-1 blockade combination in soft tissue sarcoma

2021 ◽  
Vol 9 (2) ◽  
pp. e001696
Author(s):  
Yi Que ◽  
Xiao-Long Zhang ◽  
Ze-Xian Liu ◽  
Jing-Jing Zhao ◽  
Qiu-Zhong Pan ◽  
...  
Keyword(s):  
Cell Death ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Programmed Cell Death ◽  
Gene Family ◽  
Murine Model ◽  
Immune Checkpoint ◽  
Drug Target ◽  
Class I ◽  
Mechanistic Study

BackgroundThe advent of immune checkpoint therapy has been a tremendous advance in cancer treatment. However, the responses are still insufficient in patients with soft tissue sarcoma (STS). We aimed to identify rational combinations to increase the response to immune checkpoint therapy and improve survival.MethodsWhole-exome sequencing (WES) was performed in 11 patients with liposarcoma. Somatic copy number alterations (SCNAs) were analyzed at the gene level to identify obvious amplification patterns in drug-target genes. The expression and prognostic value of class I histone deacetylases (HDACs) was evaluated in 49 patients with sarcoma in our center and confirmed in 263 sarcoma samples from The Tumor Cancer Genome Atlas (TCGA) database. Q-PCR, flow cytometry and RNA-seq were performed to determine the correlations between class I HDACs, chidamide and PD-L1 in vitro and in vivo. The efficacy of combining chidamide with PD-1 blockade was explored in an immunocompetent murine model and a small cohort of patients with advanced sarcoma. Western blot, ChIP assay and dual luciferase assessment were applied in the mechanistic study.ResultsThe HDAC gene family was frequently amplified in STS. SCNAs in the HDAC gene family were extensively amplified in 8 of 11 (73%) patients with liposarcoma, based on a drug-target gene set, and we verified amplification in 76.65% (197/257) of cases by analyzing TCGA sarcoma cohort. Class I HDAC expression is associated with a poor prognosis for patients with STS, and its inhibition is responsible for promoting apoptosis and upregulating of programmed cell death ligand 1 (PD-L1). The HDAC class I inhibitor chidamide significantly increases PD-L1 expression, increased the infiltration of CD8+ T cells and reduced the number of MDSCs in the tumor microenvironment. The combination of chidamide with an anti-PD-1 antibody significantly promotes tumor regression and improves survival in a murine model. Moreover, chidamide combined with the anti-PD-1 antibody toripalimab is effective in patients with advanced and metastatic sarcoma, and the side effects are tolerable. Mechanistically, chidamide increases histone acetylation at the PD-L1 gene through the activation of the transcriptional factor STAT1.ConclusionsThe combination of chidamide and anti-programmed cell death 1 (PD-1) therapy represents a potentially important strategy for STS.

scholarly journals Amino acid residues modulating the activities of staphylococcal glutamyl endopeptidases

2010 ◽  
Vol 391 (10) ◽  
Author(s):  
Toshio Ono ◽  
Yuko Ohara-Nemoto ◽  
Yu Shimoyama ◽  
Hisami Okawara ◽  
Takeshi Kobayakawa ◽  
...  
Keyword(s):  
Family Members ◽  
Glutamyl Endopeptidase ◽  
Peptidase Activity ◽  
Amino Acid Residues ◽  
Virulence Determinants ◽  
Cloning And Sequencing ◽  
New Family ◽  
The Family ◽  
N Terminus ◽  
Staphylococcus Epidermis

AbstractThe glutamyl endopeptidase family of enzymes from staphylococci has been shown to be important virulence determinants of pathogenic family members, such asStaphylococcus aureus. Previous studies have identified the N-terminus and residues from positions 185–195 as potentially important regions that determine the activity of three members of the family. Cloning and sequencing of the new family members fromStaphylococcus caprae(GluScpr) andStaphylococcus cohnii(GluScoh) revealed that the N-terminal Val residue is maintained in all family members. Mutants of the GluV8 enzyme fromS. aureuswith altered N-terminal residues, including amino acids with similar properties, were inactive, indicating that the Val residue is specifically required at the N-terminus of this enzyme family in order for them to function correctly. Recombinant GluScpr was found to have peptidase activity intermediate between GluV8 and GluSE fromStaphylococcus epidermisand to be somewhat less specific in its substrate requirements than other family members. The 185–195 region was found to contribute to the activity of GluScpr, although other regions of the enzyme must also play a role in defining the activity. Our results strongly indicate the importance of the N-terminal and the 185–195 region in the activity of the glutamyl endopeptidases of staphylococci.

The extensin gene family in oilseed rape (Brassica napus L.): Characterisation of sequences of representative members of the family

1990 ◽  
Vol 223 (2) ◽  
pp. 273-287 ◽  
Author(s):  
I. Marta Evans ◽  
Laurence N. Gatehouse ◽  
John A. Gatehouse ◽  
Jennifer N. Yarwood ◽  
Donald Boulter ◽  
...  
Keyword(s):  
Brassica Napus ◽  
Gene Family ◽  
Oilseed Rape ◽  
Brassica Napus L ◽  
The Family

scholarly journals Planarian cell number depends on blitzschnell, a novel gene family that balances cell proliferation and cell death

Development ◽  
2020 ◽  
Vol 147 (7) ◽  
pp. dev184044 ◽  
Author(s):  
Eudald Pascual-Carreras ◽  
Marta Marin-Barba ◽  
Carlos Herrera-Úbeda ◽  
Daniel Font-Martín ◽  
Kay Eckelt ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Gene Family ◽  
Cell Number ◽  
Novel Gene

scholarly journals Characterization and Incidence of the First Member of the Genus Mitovirus Identified in the Phytopathogenic Species Fusarium oxysporum

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 279 ◽  
Author(s):  
Almudena Torres-Trenas ◽  
Encarnación Pérez-Artés
Keyword(s):  
Phylogenetic Analysis ◽  
Amino Acid ◽  
Genetic Code ◽  
Fusarium Oxysporum ◽  
Amino Acid Residues ◽  
Fusarium Spp ◽  
Stem Loop ◽  
Universal Genetic Code ◽  
The Family ◽  
Amino Acid Tryptophan

A novel mycovirus named Fusarium oxysporum f. sp. dianthi mitovirus 1 (FodMV1) has been identified infecting a strain of Fusarium oxysporum f. sp. dianthi from Colombia. The genome of FodMV1 is 2313 nt long, and comprises a 172-nt 5’-UTR, a 2025-nt single ORF encoding an RdRp of 675 amino acid residues, and a 113-nt 3´-UTR. Homology BlastX searches identifies FodMV1 as a novel member of the genus Mitovirus in the family Narnaviridae. As the rest of mitoviruses, the genome of FodMV1 presents a high percentage of A+U (58.8%) and contains a number of UGA codons that encode the amino acid tryptophan rather than acting as stop codons as in the universal genetic code. Another common feature with other mitoviruses is that the 5′- and 3′-UTR regions of FodMV1 can be folded into potentially stable stem-loop structures. Result from phylogenetic analysis place FodMV1 in a different clade than the rest of mitoviruses described in other Fusarium spp. Incidence of FodMV1-infections in the collection of F. oxysporum f. sp. dianthi isolates analyzed is relatively high. Of particular interest is the fact that FodMV1 has been detected infecting isolates from two geographical areas as distant as Spain and Colombia.

scholarly journals Phylogenetic Relationships Within the Family Potyviridae: Wheat Streak Mosaic Virus and Brome Streak Mosaic Virus Are Not Members of the Genus Rymovirus

1998 ◽  
Vol 88 (8) ◽  
pp. 782-787 ◽  
Author(s):  
Drake C. Stenger ◽  
Jeffrey S. Hall ◽  
Il-Ryong Choi ◽  
Roy French
Keyword(s):  
Mosaic Virus ◽  
Type Species ◽  
Common Ancestor ◽  
Phylogenetic Analyses ◽  
Wheat Streak Mosaic Virus ◽  
Recent Common Ancestor ◽  
Amino Acid Residues ◽  
Most Recent Common Ancestor ◽  
The Family ◽  
Eriophyid Mites

The complete nucleotide sequence of wheat streak mosaic virus (WSMV) has been determined based on complementary DNA clones derived from the 9,384-nucleotide (nt) RNA of the virus. The genome of WSMV has a 130-nt 5′ leader and 149-nt 3′-untranslated region and is polyadenylated at the 3′ end. WSMV RNA encodes a single polyprotein of 3,035 amino acid residues and has a deduced genome organization typical for a member of the family Potyviridae (5′-P1/HC-Pro/P3/6K1/CI/6K2/VPg-NIa/NIb/CP-3′). Because WSMV shares with ryegrass mosaic virus (RGMV) the biological property of transmission by eriophyid mites, WSMV has been assigned to the genus Rymovirus, of which RGMV is the type species. Phylogenetic analyses were conducted with complete polyprotein or NIb protein sequences of 11 members of the family Potyviridae, including viruses of monocots or dicots and viruses transmitted by aphids, whiteflies, and mites. WSMV and the monocot-infecting, mite-transmitted brome streak mosaic virus (BrSMV) are sister taxa and share a most recent common ancestor with the whitefly-transmitted sweet potato mild mottle virus, the type species of the proposed genus “Ipomovirus.” In contrast, RGMV shares a most recent common ancestor with aphid-transmitted species of the genus Potyvirus. These results indicate that WSMV and BrSMV should be classified within a new genus of the family Potyviridae and should not be considered species of the genus Rymovirus.

scholarly journals Pervasive Purifying Selection Characterizes the Evolution of I2 Homologs

2006 ◽  
Vol 19 (3) ◽  
pp. 288-303 ◽  
Author(s):  
Brett C. Couch ◽  
Russ Spangler ◽  
Christine Ramos ◽  
Georgiana May
Keyword(s):  
Amino Acid ◽  
Gene Family ◽  
General Pattern ◽  
Purifying Selection ◽  
Gene Family Evolution ◽  
Death Process ◽  
Phylogenetic Distance ◽  
R Gene ◽  
The Family ◽  
Codon Positions

We sampled 384 sequences related to the Solanum pimpinel-lifolium (=Lycopersicon pimpinellifolium) disease resistance (R) gene I2 from six species, potato, S. demissum, tomato, eggplant, pepper, and tobacco. These species represent increasing phylogenetic distance from potato to tobacco, within the family Solanaceae. Using sequence data from the nucleotide binding site (NBS) region of this gene, we tested models of gene family evolution and inferred patterns of selection acting on the NBS gene region and I2 gene family. We find that the I2 family has diversified within the family Solanaceae for at least 14 million years and evolves through a slow birth-and-death process requiring approximately 12 million years to homogenize gene copies within a species. Analyses of selection resolved a general pattern of strong purifying selection acting on individual codon positions within the NBS and on NBS lineages through time. Surprisingly, we find nine codon positions strongly affected by positive selection and six pairs of codon positions demonstrating correlated amino acid substitutions. Evolutionary analyses serve as bioinformatic tools with which to sort through the vast R gene diversity in plants and find candidates for new resistance specificities or to identify specific amino acid positions important for biochemical function. The slow birth-and-death evolution of I2 genes suggests that some NBS-leucine rich repeat-mediated resistances may not be overcome rapidly by virulence evolution and that the natural diversity of R genes is a potentially valuable source for durable resistance.

scholarly journals Peptidase E, a Peptidase Specific for N-Terminal Aspartic Dipeptides, Is a Serine Hydrolase

2000 ◽  
Vol 182 (9) ◽  
pp. 2536-2543 ◽  
Author(s):  
Rachel A. L. Lassy ◽  
Charles G. Miller
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Site Directed Mutagenesis ◽  
Amino Acid Residues ◽  
Serine Hydrolase ◽  
Genome Sequences ◽  
New Family ◽  
The Family ◽  
Serovar Typhimurium ◽  
Structural Classes

ABSTRACT Salmonella enterica serovar Typhimurium peptidase E (PepE) is an N-terminal Asp-specific dipeptidase. PepE is not inhibited by any of the classical peptidase inhibitors, and its amino acid sequence does not place it in any of the known peptidase structural classes. A comparison of the amino acid sequence of PepE with a number of related sequences has allowed us to define the amino acid residues that are strongly conserved in this family. To ensure the validity of this comparison, we have expressed one of the most distantly related relatives (Xenopus) in Escherichia coli and have shown that it is indeed an Asp-specific dipeptidase with properties very similar to those of serovar Typhimurium PepE. The sequence comparison suggests that PepE is a serine hydrolase. We have used site-directed mutagenesis to change all of the conserved Ser, His, and Asp residues and have found that Ser120, His157, and Asp135 are all required for activity. Conversion of Ser120 to Cys leads to severely reduced (104-fold) but still detectable activity, and this activity but not that of the parent is inhibited by thiol reagents; these results confirm that this residue is likely to be the catalytic nucleophile. These results suggest that PepE is the prototype of a new family of serine peptidases. The phylogenetic distribution of the family is unusual, since representatives are found in eubacteria, an insect (Drosophila), and a vertebrate (Xenopus) but not in the Archaea or in any of the other eukaryotes for which genome sequences are available.

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