scholarly journals Comparative Genomic Analysis and a Novel Set of Missense Mutation of the Leptospira weilii Serogroup Mini From the Urine of Asymptomatic Dogs in Thailand

2021 ◽  
Vol 12 ◽  
Author(s):  
Alongkorn Kurilung ◽  
Vincent Perreten ◽  
Nuvee Prapasarakul
Keyword(s):  
Molecular Mechanisms ◽  
Genome Structure ◽  
Ecological Niches ◽  
Comparative Genomic ◽  
Genomic Feature ◽  
Missense Mutations ◽  
Limited Information ◽  
High Genetic Diversity ◽  
Pan Genome ◽  
Pathogenesis Related

Leptospira weilii belongs to the pathogenic Leptospira group and is a causal agent of human and animal leptospirosis in many world regions. L. weilii can produce varied clinical presentations from asymptomatic through acute to chronic infections and occupy several ecological niches. Nevertheless, the genomic feature and genetic basis behind the host adaptability of L. weilii remain elusive due to limited information. Therefore, this study aimed to examine the complete circular genomes of two new L. weilii serogroup Mini strains (CUDO6 and CUD13) recovered from the urine of asymptomatic dogs in Thailand and then compared with the 17 genomes available for L. weilii. Variant calling analysis (VCA) was also undertaken to gain potential insight into the missense mutations, focusing on the known pathogenesis-related genes. Whole genome sequences revealed that the CUDO6 and CUD13 strains each contained two chromosomes and one plasmid, with average genome size and G+C content of 4.37 Mbp and 40.7%, respectively. Both strains harbored almost all the confirmed pathogenesis-related genes in Leptospira. Two novel plasmid sequences, pDO6 and pD13, were identified in the strains CUDO6 and CUD13. Both plasmids contained genes responsible for stress response that may play important roles in bacterial adaptation during persistence in the kidneys. The core-single nucleotide polymorphisms phylogeny demonstrated that both strains had a close genetic relationship. Amongst the 19 L. weilii strains analyzed, the pan-genome analysis showed an open pan-genome structure, correlated with their high genetic diversity. VCA identified missense mutations in genes involved in endoflagella, lipopolysaccharide (LPS) structure, mammalian cell entry protein, and hemolytic activities, and may be associated with host-adaptation in the strains. Missense mutations of the endoflagella genes of CUDO6 and CUD13 were associated with loss of motility. These findings extend the knowledge about the pathogenic molecular mechanisms and genomic evolution of this important zoonotic pathogen.

scholarly journals Pan-genome analyses of peach and its wild relatives provide insights into the genetics of disease resistance and species adaptation

2020 ◽  
Author(s):  
Ke Cao ◽  
Zhen Peng ◽  
Xing Zhao ◽  
Yong Li ◽  
Kuozhan Liu ◽  
...  
Keyword(s):  
High Altitude ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Genomic Analysis ◽  
Gene Families ◽  
Wild Relatives ◽  
Comparative Genomic ◽  
High Altitude Adaptation ◽  
Pan Genome ◽  
Altitude Adaptation

AbstractAs a foundation to understand the molecular mechanisms of peach evolution and high-altitude adaptation, we performed de novo genome assembling of four wild relatives of P. persica, P. mira, P. kansuensis, P. davidiana and P. ferganensis. Through comparative genomic analysis, abundant genetic variations were identified in four wild species when compared to P. persica. Among them, a deletion, located at the promoter of Prupe.2G053600 in P. kansuensis, was validated to regulate the resistance to nematode. Next, a pan-genome was constructed which comprised 15,216 core gene families among four wild peaches and P. perisca. We identified the expanded and contracted gene families in different species and investigated their roles during peach evolution. Our results indicated that P. mira was the primitive ancestor of cultivated peach, and peach evolution was non-linear and a cross event might have occurred between P. mira and P. dulcis during the process. Combined with the selective sweeps identified using accessions of P. mira originating from different altitude regions, we proposed that nitrogen recovery was essential for high-altitude adaptation of P. mira through increasing its resistance to low temperature. The pan-genome constructed in our study provides a valuable resource for developing elite cultivars, studying the peach evolution, and characterizing the high-altitude adaptation in perennial crops.

scholarly journals Genomic dissection of the most prevalent Listeria monocytogenes clone, sequence type ST87, in China

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Yan Wang ◽  
Lijuan Luo ◽  
Qun Li ◽  
Hong Wang ◽  
Yiqian Wang ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Core Genome ◽  
Major Gene ◽  
Sequence Type ◽  
Whole Genome Sequence ◽  
Ecological Niches ◽  
Comparative Genomic ◽  
High Genetic Diversity ◽  
Modification System ◽  
Diverse Range

Abstract Background Listeria monocytogenes consists of four lineages that occupy a wide variety of ecological niches. Sequence type (ST) 87 (serotype 1/2b), belonging to lineage I, is one of the most common STs isolated from food products, food associated environments and sporadic listeriosis in China. Here, we performed a comparative genomic analysis of the L. monocytogenes ST87 clone by sequencing 71 strains representing a diverse range of sources, different geographical locations and isolation years. Results The core genome and pan genome of ST87 contained 2667 genes and 3687 genes respectively. Phylogenetic analysis based on core genome SNPs divided the 71 strains into 10 clades. The clinical strains were distributed among multiple clades. Four clades contained strains from multiple geographic regions and showed high genetic diversity. The major gene content variation of ST87 genomes was due to putative prophages, with eleven hotspots of the genome that harbor prophages. All strains carry an intact CRISRP/Cas system. Two major CRISPR spacer profiles were found which were not clustered phylogenetically. A large plasmid of about 90 Kb, which carried heavy metal resistance genes, was found in 32.4% (23/71) of the strains. All ST87 strains harbored the Listeria pathogenicity island (LIPI)-4 and a unique 10-open read frame (ORF) genomic island containing a novel restriction-modification system. Conclusion Whole genome sequence analysis of L. monocytogenes ST87 enabled a clearer understanding of the population structure and the evolutionary history of ST87 L. monocytogenes in China. The novel genetic elements identified may contribute to its virulence and adaptation to different environmental niches. Our findings will be useful for the development of effective strategies for the prevention and treatment of listeriosis caused by this prevalent clone.

scholarly journals Genome Sequencing Analysis of Scleromitrula shiraiana, a Causal Agent of Mulberry Sclerotial Disease With Narrow Host Range

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhiyuan Lv ◽  
Ziwen He ◽  
Lijuan Hao ◽  
Xin Kang ◽  
Bi Ma ◽  
...  
Keyword(s):  
Host Range ◽  
Molecular Mechanisms ◽  
Genomic Analysis ◽  
Effector Proteins ◽  
Ecological Niches ◽  
Comparative Genomic ◽  
Sequencing Analysis ◽  
Cell Wall Degrading Enzymes ◽  
Narrow Host Range ◽  
Genes Encoding

Scleromitrula shiraiana is a necrotrophic fungus with a narrow host range, and is one of the main causal pathogens of mulberry sclerotial disease. However, its molecular mechanisms and pathogenesis are unclear. Here, we report a 39.0 Mb high-quality genome sequence for S. shiraiana strain SX-001. The S. shiraiana genome contains 11,327 protein-coding genes. The number of genes and genome size of S. shiraiana are similar to most other Ascomycetes. The cross-similarities and differences of S. shiraiana with the closely related Sclerotinia sclerotiorum and Botrytis cinerea indicated that S. shiraiana differentiated earlier from their common ancestor. A comparative genomic analysis showed that S. shiraiana has fewer genes encoding cell wall-degrading enzymes (CWDEs) and effector proteins than that of S. sclerotiorum and B. cinerea, as well as many other Ascomycetes. This is probably a key factor in the weaker aggressiveness of S. shiraiana to other plants. S. shiraiana has many species-specific genes encoding secondary metabolism core enzymes. The diversity of secondary metabolites may be related to the adaptation of these pathogens to specific ecological niches. However, melanin and oxalic acid are conserved metabolites among many Sclerotiniaceae fungi, and may be essential for survival and infection. Our results provide insights into the narrow host range of S. shiraiana and its adaptation to mulberries.

scholarly journals Unveiling the Dynamics of KRAS4b on Lipid Model Membranes

2021 ◽  
Author(s):  
Cesar A. López ◽  
Animesh Agarwal ◽  
Que N. Van ◽  
Andrew G. Stephen ◽  
S. Gnanakaran
Keyword(s):  
Molecular Mechanisms ◽  
Hypervariable Region ◽  
Small Gtpase ◽  
Model Systems ◽  
Coarse Grained ◽  
Regulatory Function ◽  
Limited Information ◽  
Long Time ◽  
Cell Growth And Differentiation ◽  
State Models

AbstractSmall GTPase proteins are ubiquitous and responsible for regulating several processes related to cell growth and differentiation. Mutations that stabilize their active state can lead to uncontrolled cell proliferation and cancer. Although these proteins are well characterized at the cellular scale, the molecular mechanisms governing their functions are still poorly understood. In addition, there is limited information about the regulatory function of the cell membrane which supports their activity. Thus, we have studied the dynamics and conformations of the farnesylated KRAS4b in various membrane model systems, ranging from binary fluid mixtures to heterogeneous raft mimics. Our approach combines long time-scale coarse-grained (CG) simulations and Markov state models to dissect the membrane-supported dynamics of KRAS4b. Our simulations reveal that protein dynamics is mainly modulated by the presence of anionic lipids and to some extent by the nucleotide state (activation) of the protein. In addition, our results suggest that both the farnesyl and the polybasic hypervariable region (HVR) are responsible for its preferential partitioning within the liquid-disordered (Ld) domains in membranes, potentially enhancing the formation of membrane-driven signaling platforms. Graphic Abstract

Population genetic structure and dispersal of Pinus occidentalis in the Dominican Republic by chloroplastic SSR with implications for its conservation, management, and reforestation

2021 ◽  
Author(s):  
Luis E. Rodríguez de Francisco ◽  
Rosanna Carreras-De León ◽  
Rafael M. Navarro Cerrillo ◽  
Liz A. Paulino-Gervacio ◽  
María-Dolores Rey ◽  
...  
Keyword(s):  
Genetic Structure ◽  
Dominican Republic ◽  
Population Genetic Structure ◽  
Population Genetic ◽  
Conservation Management ◽  
Natural Populations ◽  
Limited Information ◽  
High Genetic Diversity ◽  
The Impact ◽  
Pinus Occidentalis

<i>Pinus occidentalis</i> is the dominant species of forest ecosystems in the Dominican Republic, located between 200 and 3000 meters above sea level, with extensive and overexploited natural populations. However, over the years, various restoration plans have been performed, which could affect the genetic structure of <i>P. occidentalis</i>. Despite being the species with the highest occurrence in the Dominican forests, there is no existing information on genetic structure and molecular characterization among natural populations with limited information on both phenological and productive characterization. In this study, the genetic structure, diversity, and gene flow of the five <i>P. occidentalis</i> natural populations of the Dominican Republic were determined using microsatellite markers. A total of 145 individuals were genotyped with eight polymorphic chloroplastic microsatellites, producing an average of 41 haplotypes with high genetic diversity across populations (H<sub>E</sub> = 0.90). Significant population genetic structure was found between populations (F<sub>ST</sub> = 0.123). These results reflect the impact of reforestation programs on natural populations and diluting the natural genetic signature. Analysis of population genetic data is, therefore, crucial for the breeding and conservation programs of <i>P. occidentalis</i> in the country.

scholarly journals Elucidation of molecular mechanisms of flower form development in tree peony ( Paeonia suffriticosa ) through comparative transcriptome analysis of floral parts

2019 ◽  
Author(s):  
Jiuxing Lu ◽  
Yun Zheng ◽  
Haoning Wang ◽  
Zheng Wang ◽  
Yonghua Li ◽  
...  
Keyword(s):  
Woody Plants ◽  
Molecular Mechanisms ◽  
High Expression ◽  
Limited Information ◽  
Mads Box ◽  
Mads Box Genes ◽  
Tree Peony ◽  
Expression Levels ◽  
Key Genes ◽  
Flower Form

Abstract Background: Tree peony (Paeonia suffruticasa) is an economically, medicinally ornamentally important woody flowering woody plants in East Asia and is a common also ornamental shrub in Europe and North America. It is well known and prized for their beautiful flowers in many different forms. Samen petalody has been shown to be the most effective way to modify flower forms. However, there is limited information on the molecular mechanisms of stamen petalody and flower form formation in tree peony.Results: In this study, RNA sequencing was used to assemble and annotate the unigenes in the tree peony to identify the critical genes related to flower parts formation and verify the key genes in different flower forms of tree peony cultivar. A total of 76,007 high quality unigenes were assembled and 30,505 were successfully annotated. A total of 1,833 TFs were identified in our study, among them 16 MADS-box genes were found and characterized. Six key genes were selected to verity their functions in stamen petalody. AG and SEP showed high expression level in carpals and sepals separately both in stamen petalody group and non-stamen petalody groups. PI and AP3 showed high expression levels in inter-petals in stamen petalody groups than in staments in non-stamen petalody.Conclusion: Sixteen MADS-box genes were identified for the first time in tree peony through RNA-seq method. We identified six key genes based on their differential expression levels in different flower parts. These six key genes represented all categories in the ABCDE model to verify the functions in stamen petalody. PI and AP3 were verified to likely play important roles in regulating stamen petalody in tree peony. Our study has helped establish the flower development model in tree peony, identified key molecular mechanisms in the development of different flower forms, and provided valuable information in improving genetic diversity of tree peony and many other woody plants.

scholarly journals Widespread alteration of protein autoinhibition in human cancers

2018 ◽  
Author(s):  
Ashwani Jha ◽  
Jennifer M. Bui ◽  
Dokyun Na ◽  
Jörg Gsponer
Keyword(s):  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Signal Propagation ◽  
Genetic Alterations ◽  
Missense Mutations ◽  
Pathway Activation ◽  
Tumorigenic Potential ◽  
Significant Enrichment ◽  
Cancer Types ◽  
Cancer Drivers

ABSTRACTAutoinhibition is a prevalent allosteric regulatory mechanism in signaling proteins as it prevents spurious pathway activation and primes for signal propagation only under appropriate inputs. Altered functioning of inhibitory allosteric switches underlies the tumorigenic potential of numerous cancer drivers. However, whether protein autoinhibition is altered generically in cancer cells remains elusive. Here, we reveal that cancer-associated missense mutations and fusion breakpoints are found with significant enrichment within inhibitory allosteric switches across all cancer types, which in the case of the fusion breakpoints is specific to cancer and not present in other diseases. Recurrently disrupted or mutated allosteric switches identify established and new cancer drivers. Cancer-specific mutations in allosteric switches are associated with distinct changes in signaling, and suggest molecular mechanisms for altered protein regulation, which in the case of ASK1, DAPK2 and EIF4G1 were supported by biophysical simulations. Our results demonstrate that autoinhibition-modulating genetic alterations are positively selected for by cancer cells, and that their study provides valuable insights into molecular mechanisms of cancer misregulation.

scholarly journals Molecular Mechanisms of Disease-Causing Missense Mutations

2013 ◽  
Vol 425 (21) ◽  
pp. 3919-3936 ◽  
Author(s):  
Shannon Stefl ◽  
Hafumi Nishi ◽  
Marharyta Petukh ◽  
Anna R. Panchenko ◽  
Emil Alexov
Keyword(s):  
Molecular Mechanisms ◽  
Missense Mutations

Abstract TP269: Distinct Molecular Mechanisms of Htra1 Mutants in Manifesting Heterozygotes With Carasil

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Hiroaki Nozaki ◽  
Taisuke Kato ◽  
Megumi Nihonmatsu ◽  
Yohei Saito ◽  
Ikuko Mizuta ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Molecular Mechanisms ◽  
Small Vessel Disease ◽  
Gel Filtration ◽  
Gene Mutations ◽  
Missense Mutations ◽  
Inherited Disease ◽  
Wild Type ◽  
Vessel Disease ◽  
Activation Cascade

Introduction: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), an autosomal recessive inherited cerebral small vessel disease (CSVD), involves severe leukoaraiosis, multiple lacunar infarcts, early-onset alopecia, and spondylosis deformans. High-temperature requirement serine peptidase A1 (HTRA1) gene mutations cause CARASIL by decreasing HTRA1 protease activity. Although CARASIL is a recessive inherited disease, heterozygous mutations in the HTRA1 gene were recently identified in 11 families with CSVD. Because CSVD is frequently observed in elderly individuals, it is unclear which mutants truly contribute to CSVD pathogenesis. Here, we found heterozygous mutations in the HTRA1 gene in individuals with CSVD and investigated the differences in biochemical characteristics between these mutant HTRA1s and mutant HTRA1s observed in homozygotes. Methods: We recruited 113 unrelated index patients with clinically diagnosed CSVD. The coding sequences of the HTRA1 gene were analyzed. We evaluated HTRA1 protease activities using casein assays and oligomeric HTRA1 formation using gel filtration chromatography. Results: We found 4 heterozygous missense mutations in the HTRA1 gene (p.G283E, p.P285L, p.R302Q, and p.T319I) in 6 patients from 113 unrelated index patients and in 2 siblings in 2 unrelated families with p.R302Q. These mutant HTRA1s showed markedly decreased protease activities and inhibited wild-type HTRA1 activity, whereas 2 of 3 mutant HTRA1s reported in CARASIL (A252T and V297M) did not inhibit wild- type HTRA1 activity. Wild-type HTRA1 forms trimers; however, G283E and T319I HTRA1, observed in manifesting heterozygotes, did not form trimers. P285L and R302Q HTRA1s formed trimers, but their mutations were located in domains that are important for trimer-associated HTRA1 activation; in contrast, A252T and V297M HTRA1s, which have been observed in CARASIL, also formed trimers but had mutations outside the domains important for trimer- associated HTRA1 activation. Conclusions: The mutant HTRA1s observed in manifesting heterozygotes might result in an impaired HTRA1 activation cascade of HTRA1 or be unable to form stable trimers.

Sign in / Sign up

Export Citation Format

Share Document