scholarly journals Natural variation in sugar tolerance associates with changes in signaling and mitochondrial ribosome biogenesis

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Richard G Melvin ◽  
Nicole Lamichane ◽  
Essi Havula ◽  
Krista Kokki ◽  
Charles Soeder ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Ribosome Biogenesis ◽  
Genomic Variation ◽  
Optimal Range ◽  
Macronutrient Composition ◽  
Generalist Species ◽  
Sugar Tolerance ◽  
Metabolic Gene Expression ◽  
Mitochondrial Ribosome ◽  
Genomic Regions

How dietary selection affects genome evolution to define the optimal range of nutrient intake is a poorly understood question with medical relevance. We have addressed this question by analyzing Drosophila simulans and sechellia, recently diverged species with differential diet choice. D. sechellia larvae, specialized to a nutrient scarce diet, did not survive on sugar-rich conditions, while the generalist species D. simulans was sugar tolerant. Sugar tolerance in D. simulans was a tradeoff for performance on low-energy diet and was associated with global reprogramming of metabolic gene expression. Hybridization and phenotype-based introgression revealed the genomic regions of D. simulans that were sufficient for sugar tolerance. These regions included genes that are involved in mitochondrial ribosome biogenesis and intracellular signaling, such as PPP1R15/Gadd34 and SERCA, which contributed to sugar tolerance. In conclusion, genomic variation affecting genes involved in global metabolic control defines the optimal range for dietary macronutrient composition.

scholarly journals Author response: Natural variation in sugar tolerance associates with changes in signaling and mitochondrial ribosome biogenesis

2018 ◽  
Author(s):  
Richard G Melvin ◽  
Nicole Lamichane ◽  
Essi Havula ◽  
Krista Kokki ◽  
Charles Soeder ◽  
...  
Keyword(s):  
Ribosome Biogenesis ◽  
Natural Variation ◽  
Author Response ◽  
Sugar Tolerance ◽  
Mitochondrial Ribosome

scholarly journals Assessing genomic diversity and signatures of selection in Jiaxian Red cattle using whole-genome sequencing data

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xiaoting Xia ◽  
Shunjin Zhang ◽  
Huaju Zhang ◽  
Zijing Zhang ◽  
Ningbo Chen ◽  
...  
Keyword(s):  
Population Structure ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genomic Variation ◽  
Genomic Diversity ◽  
System Response ◽  
Whole Genome ◽  
Population Structure Analysis ◽  
Native Cattle ◽  
Genomic Regions

Abstract Background Native cattle breeds are an important source of genetic variation because they might carry alleles that enable them to adapt to local environment and tough feeding conditions. Jiaxian Red, a Chinese native cattle breed, is reported to have originated from crossbreeding between taurine and indicine cattle; their history as a draft and meat animal dates back at least 30 years. Using whole-genome sequencing (WGS) data of 30 animals from the core breeding farm, we investigated the genetic diversity, population structure and genomic regions under selection of Jiaxian Red cattle. Furthermore, we used 131 published genomes of world-wide cattle to characterize the genomic variation of Jiaxian Red cattle. Results The population structure analysis revealed that Jiaxian Red cattle harboured the ancestry with East Asian taurine (0.493), Chinese indicine (0.379), European taurine (0.095) and Indian indicine (0.033). Three methods (nucleotide diversity, linkage disequilibrium decay and runs of homozygosity) implied the relatively high genomic diversity in Jiaxian Red cattle. We used θπ, CLR, FST and XP-EHH methods to look for the candidate signatures of positive selection in Jiaxian Red cattle. A total number of 171 (θπ and CLR) and 17 (FST and XP-EHH) shared genes were identified using different detection strategies. Functional annotation analysis revealed that these genes are potentially responsible for growth and feed efficiency (CCSER1), meat quality traits (ROCK2, PPP1R12A, CYB5R4, EYA3, PHACTR1), fertility (RFX4, SRD5A2) and immune system response (SLAMF1, CD84 and SLAMF6). Conclusion We provide a comprehensive overview of sequence variations in Jiaxian Red cattle genomes. Selection signatures were detected in genomic regions that are possibly related to economically important traits in Jiaxian Red cattle. We observed a high level of genomic diversity and low inbreeding in Jiaxian Red cattle. These results provide a basis for further resource protection and breeding improvement of this breed.

scholarly journals Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hauke S. Hillen ◽  
Elena Lavdovskaia ◽  
Franziska Nadler ◽  
Elisa Hanitsch ◽  
Andreas Linden ◽  
...  
Keyword(s):  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Ribosomal Subunit ◽  
Structural Basis ◽  
Peptidyl Transferase ◽  
Mitochondrial Ribosomes ◽  
Mitochondrial Ribosome ◽  
In Vitro Reconstitution

AbstractRibosome biogenesis requires auxiliary factors to promote folding and assembly of ribosomal proteins and RNA. Particularly, maturation of the peptidyl transferase center (PTC) is mediated by conserved GTPases, but the molecular basis is poorly understood. Here, we define the mechanism of GTPase-driven maturation of the human mitochondrial large ribosomal subunit (mtLSU) using endogenous complex purification, in vitro reconstitution and cryo-EM. Structures of transient native mtLSU assembly intermediates that accumulate in GTPBP6-deficient cells reveal how the biogenesis factors GTPBP5, MTERF4 and NSUN4 facilitate PTC folding. Addition of recombinant GTPBP6 reconstitutes late mtLSU biogenesis in vitro and shows that GTPBP6 triggers a molecular switch and progression to a near-mature PTC state. Additionally, cryo-EM analysis of GTPBP6-treated mature mitochondrial ribosomes reveals the structural basis for the dual-role of GTPBP6 in ribosome biogenesis and recycling. Together, these results provide a framework for understanding step-wise PTC folding as a critical conserved quality control checkpoint.

scholarly journals Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling

2021 ◽  
Author(s):  
Hauke S. Hillen ◽  
Elena Lavdovskaia ◽  
Franziska Nadler ◽  
Elisa Hanitsch ◽  
Andreas Linden ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Large Subunit ◽  
Structural Basis ◽  
Catalytic Core ◽  
Mitochondrial Ribosomes ◽  
Mitochondrial Ribosome ◽  
Translation Systems

Ribosome biogenesis is an essential process that requires auxiliary factors to promote folding and assembly of ribosomal proteins and RNA. In particular, maturation of the peptidyl transferase center (PTC), the catalytic core of the ribosome, is mediated by universally conserved GTPases, but the molecular basis is poorly understood. Here, we define the mechanism of GTPase-driven maturation of the human mitochondrial ribosomal large subunit (mtLSU) using a combination of endogenous complex purification, in vitro reconstitution and cryo-electron microscopy (cryo-EM). Structures of transient native mtLSU assembly intermediates that accumulate in GTPBP6-deficient cells reveal how the biogenesis factors GTPBP5, MTERF4 and NSUN4 facilitate PTC folding. Subsequent addition of recombinant GTPBP6 reconstitutes late mtLSU biogenesis in vitro and shows that GTPBP6 triggers a molecular switch by releasing MTERF4-NSUN4 and GTPBP5 accompanied by the progression to a near-mature PTC state. In addition, cryo-EM analysis of GTPBP6-treated mature mitochondrial ribosomes reveals the structural basis for the dual-role of GTPBP6 in ribosome biogenesis and recycling. Together, these results define the molecular basis of dynamic GTPase-mediated PTC maturation during mitochondrial ribosome biogenesis and provide a framework for understanding step-wise progression of PTC folding as a critical quality control checkpoint in all translation systems.

scholarly journals Human Cytomegalovirus Infection Upregulates the Mitochondrial Transcription and Translation Machineries

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
S. Karniely ◽  
M. P. Weekes ◽  
R. Antrobus ◽  
J. Rorbach ◽  
L. van Haute ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Human Cytomegalovirus ◽  
Mitochondrial Biogenesis ◽  
Ribosome Biogenesis ◽  
Hcmv Infection ◽  
Aerobic Glycolysis ◽  
Tricarboxylic Acid Cycle ◽  
Mitochondrial Translation ◽  
Mitochondrial Transcription ◽  
Mitochondrial Ribosome

ABSTRACT Infection with human cytomegalovirus (HCMV) profoundly affects cellular metabolism. Like in tumor cells, HCMV infection increases glycolysis, and glucose carbon is shifted from the mitochondrial tricarboxylic acid cycle to the biosynthesis of fatty acids. However, unlike in many tumor cells, where aerobic glycolysis is accompanied by suppression of mitochondrial oxidative phosphorylation, HCMV induces mitochondrial biogenesis and respiration. Here, we affinity purified mitochondria and used quantitative mass spectrometry to determine how the mitochondrial proteome changes upon HCMV infection. We found that the mitochondrial transcription and translation systems are induced early during the viral replication cycle. Specifically, proteins involved in biogenesis of the mitochondrial ribosome were highly upregulated by HCMV infection. Inhibition of mitochondrial translation with chloramphenicol or knockdown of HCMV-induced ribosome biogenesis factor MRM3 abolished the HCMV-mediated increase in mitochondrially encoded proteins and significantly impaired viral growth under bioenergetically restricting conditions. Our findings demonstrate how HCMV manipulates mitochondrial biogenesis to support its replication. IMPORTANCE Human cytomegalovirus (HCMV), a betaherpesvirus, is a leading cause of morbidity and mortality during congenital infection and among immunosuppressed individuals. HCMV infection significantly changes cellular metabolism. Akin to tumor cells, in HCMV-infected cells, glycolysis is increased and glucose carbon is shifted from the tricarboxylic acid cycle to fatty acid biosynthesis. However, unlike in tumor cells, HCMV induces mitochondrial biogenesis even under aerobic glycolysis. Here, we have affinity purified mitochondria and used quantitative mass spectrometry to determine how the mitochondrial proteome changes upon HCMV infection. We find that the mitochondrial transcription and translation systems are induced early during the viral replication cycle. Specifically, proteins involved in biogenesis of the mitochondrial ribosome were highly upregulated by HCMV infection. Inhibition of mitochondrial translation with chloramphenicol or knockdown of HCMV-induced ribosome biogenesis factor MRM3 abolished the HCMV-mediated increase in mitochondrially encoded proteins and significantly impaired viral growth. Our findings demonstrate how HCMV manipulates mitochondrial biogenesis to support its replication.

Genomics: the host's genotype and its relevance to bovine respiratory disease

2020 ◽  
pp. 1-5
Author(s):  
Holly Neibergs
Keyword(s):  
Dairy Cattle ◽  
Respiratory Disease ◽  
Bovine Respiratory Disease ◽  
Genomic Variation ◽  
National Standards ◽  
Host Susceptibility ◽  
Association Analyses ◽  
Heritability Estimates ◽  
Definition Of ◽  
Genomic Regions

Abstract Genomic variation exists in cattle that affects their susceptibility to the complex of pathogens responsible for bovine respiratory disease (BRD). Heritability estimates and genome-wide association analyses (GWAA) support the role of host genomic variation in BRD susceptibility. Heritability estimates for BRD susceptibility range from 0.02 to 0.29 depending on the population, the definition of the disease, and the accuracy of diagnosis. GWAA have identified genomic regions (loci) associated with BRD in beef and dairy cattle based on a variety of BRD diagnostic criteria. National standards need to be developed for BRD diagnostics and reporting to facilitate selection. Commercial genotyping is available to predict BRD susceptibility in dairy cattle and for the selection of replacement animals. Disease pathogen profiles vary by region and can result in genetic heterogeneity where different loci are important for susceptibility to different BRD pathogens. Although the identification of the BRD pathogens may not be critical for treatment, it is of paramount importance in identifying loci that render cattle susceptible to the disease. Identification of loci associated with host susceptibility to BRD provides a foundation for genomic selection to reduce disease and opens the possibilities to a better understanding of how the host defends itself.

scholarly journals Adaptations to excess choline in insulin resistant and Pcyt2 deficient skeletal muscle

2017 ◽  
Vol 95 (2) ◽  
pp. 223-231 ◽  
Author(s):  
Adrian Taylor ◽  
Laila Cigana Schenkel ◽  
Maiya Yokich ◽  
Marica Bakovic
Keyword(s):  
Skeletal Muscle ◽  
Intracellular Signaling ◽  
Lipid Analysis ◽  
Choline Transport ◽  
Insulin Resistant ◽  
Expression Of Genes ◽  
Metabolic Gene Expression ◽  
Glucose Storage ◽  
Positive Effect ◽  
Deficient Mice

It was hypothesized that choline supplementation in insulin resistant (IR) CTP:phosphoethanolamine cytidylyltransferase deficient (Pcyt2+/−) mice would ameliorate muscle function by remodeling glucose and fatty acid (FA) metabolism. Pcyt2+/− mice either received no treatment or were allowed access to 2 mg/mL choline in drinking water for 4 weeks. Skeletal muscle was harvested from choline treated and untreated mice. Lipid analysis and metabolic gene expression and signaling pathways were compared between untreated Pcyt2+/− mice, treated Pcyt2+/− mice, and Pcyt2+/+ mice. The major positive effect of choline supplementation on IR muscle was the reduction of glucose utilization for FA and triglyceride (TAG) synthesis and increased muscle glucose storage as glycogen. Choline reduced the expression of genes for FA and TAG formation (Scd1, Fas, Srebp1c, Dgat1/2), upregulated the genes for FA oxidation (Cpt1, Pparα, Pgc1α), and had minor effects on phospholipid and lipolysis genes. Pcyt2+/− muscle had reduced insulin signaling (IRS1), autophagy (LC3), and choline transport (CTL1) proteins that were restored by choline treatment. Additionally, choline activated AMPK and Akt while inhibiting mTORC1 phosphorylation. These data established that choline supplementation could restore muscle glucose metabolism by reducing lipogenesis and improving mitochondrial and intracellular signaling for protein and energy metabolism in insulin resistant Pcyt2 deficient mice.

scholarly journals Genomic Comparisons of Salmonella enterica Serovar Dublin, Agona, and Typhimurium Strains Recently Isolated from Milk Filters and Bovine Samples from Ireland, Using a Salmonella Microarray

2005 ◽  
Vol 71 (3) ◽  
pp. 1616-1625 ◽  
Author(s):  
F. J. Reen ◽  
E. F. Boyd ◽  
S. Porwollik ◽  
B. P. Murphy ◽  
D. Gilroy ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Sugar Metabolism ◽  
Genomic Variation ◽  
Food Borne ◽  
Protein Encoding ◽  
Serovar Typhimurium ◽  
Food Borne Illness ◽  
Associated Proteins ◽  
Genomic Regions ◽  
Salmonella Enterica Serovar Dublin

ABSTRACT Salmonella-induced enterocolitis is the leading food-borne illness with a lethal outcome and causes millions of cases of gastroenteritis each year. We examined genomic variation among 12 environmental, veterinary, and clinical Salmonella enterica serovar Dublin, Agona, and Typhimurium strains isolated in Ireland between 2000 and 2003, as well as two clinical isolates from Canada and four archival isolates, which belonged to serovars Dublin and Agona. Using DNA-DNA hybridization to a microarray consisting of most of the predicted protein-encoding sequences of the S. enterica serovar Typhimurium LT2 genome, we identified a number of genomic regions that were absent in one or more serovars. The 34 genomic regions encoded proteins involved in sugar metabolism, transport, fimbrial and phage biogenesis, and transcriptional regulation, as well as inner and outer membrane-associated proteins. Two of the four prophages identified in strain LT2, prophages Gifsy-1 and Gifsy-2, were present in all six serovar Typhimurium strains examined. Prophage Fels-1 was absent from all 18 isolates examined, and Fels-2 was completely absent from the serovar Typhimurium isolates and the Salmonella Reference Collection B serovar Dublin strain Du2. All five Salmonella pathogenicity islands were present in all isolates. Plasmid pSLT was absent from all serovar Agona isolates, and only homologues of the spv genes were present in eight of the nine serovar Dublin strains. Only limited intraserovar diversity was found among the nine serovar Dublin, three serovar Agona, and six serovar Typhimurium isolates examined even though these isolates had extensive geographic, temporal, and source differences.

scholarly journals Genome-wide copy number variations in a large cohort of bantu African children

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Feyza Yilmaz ◽  
Megan Null ◽  
David Astling ◽  
Hung-Chun Yu ◽  
Joanne Cole ◽  
...  
Keyword(s):  
Copy Number ◽  
Developmental Disorders ◽  
African Ancestry ◽  
22Q11.2 Deletion Syndrome ◽  
Copy Number Variations ◽  
Genomic Variation ◽  
Deletion Syndrome ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Regions

Abstract Background Copy number variations (CNVs) account for a substantial proportion of inter-individual genomic variation. However, a majority of genomic variation studies have focused on single-nucleotide variations (SNVs), with limited genome-wide analysis of CNVs in large cohorts, especially in populations that are under-represented in genetic studies including people of African descent. Methods We carried out a genome-wide copy number analysis in > 3400 healthy Bantu Africans from Tanzania. Signal intensity data from high density (> 2.5 million probes) genotyping arrays were used for CNV calling with three algorithms including PennCNV, DNAcopy and VanillaICE. Stringent quality metrics and filtering criteria were applied to obtain high confidence CNVs. Results We identified over 400,000 CNVs larger than 1 kilobase (kb), for an average of 120 CNVs (SE = 2.57) per individual. We detected 866 large CNVs (≥ 300 kb), some of which overlapped genomic regions previously associated with multiple congenital anomaly syndromes, including Prader-Willi/Angelman syndrome (Type1) and 22q11.2 deletion syndrome. Furthermore, several of the common CNVs seen in our cohort (≥ 5%) overlap genes previously associated with developmental disorders. Conclusions These findings may help refine the phenotypic outcomes and penetrance of variations affecting genes and genomic regions previously implicated in diseases. Our study provides one of the largest datasets of CNVs from individuals of African ancestry, enabling improved clinical evaluation and disease association of CNVs observed in research and clinical studies in African populations.

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