Genomic diversity, chromosomal rearrangements, and interspecies hybridization in the Ogataea polymorpha species complex.
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ABSTRACT:
SUBMITTER: Hanson SJ
PROVIDER: S-EPMC8496258 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Copy number variation (CNV) is a major source of genetic variation among humans. In addition to existing as benign polymorphisms, CNVs can also convey clinical phenotypes, including genomic disorders, sporadic diseases and complex human traits. CNV results from genomic rearrangements that can represent simple deletion or duplication of a genomic segment, or be more complex. Complex chromosomal rearrangements (CCRs) have been known for some time but their mechanisms have remained elusive. Recent technology advances and high-resolution human genome analyses have revealed that complex genomic rearrangements can account for a large fraction of non-recurrent rearrangements at a given locus. Various mechanisms, most of which are DNA-replication-based, for example fork stalling and template switching (FoSTeS) and microhomology-mediated break-induced replication (MMBIR), have been proposed for generating such complex genomic rearrangements and are probably responsible for CCR.
| S-EPMC4464790 | biostudies-literature
Project description:Haemophilus influenzae(Hi) is a gram-negative rod shaped bacterium that lives symbiotically in the upper respiratory tract of humans. Capsulated Hi, as well as non-capsulated strains are known to cause a number of significant infections. Recognizing and understanding the links between the phenotypic traits and the genetic background has paramount epidemiological and clinical importance. To date, a panoply of microbiological and molecular biology tools have been developed and utilized by researchers aimed at identifying the evolutionary links among strains and isolates. Comparative genomic hybridization (CGH) has been shown to be a useful tool for screening strains for their genetic content. However, there is a major limitation when CGH is conducted on a microarray based on a single reference genome. CGH results report which genes are present or absent relative to the genome. Hence the information about novel genetic content that the query strain possesses remains obscure. We report here the construction of the first Hi pan-genome microarray representing ca. 4600 features by 70-mers. In addition to those from the Rd strain, new features originate from the unfinished genome sequences present in NCBI database and from our novel gene discovery project efforts using strain HK1212. Genomes of 20strains belonging to different phylogenetic lineages were screened for their gene loss and gain utilizing the species microarray. The results obtained by employing the multistrain species microarray provide comprehensive information about the genomic content of uncharacterized strains. The trees generated by CGH, in general, do not reproduce the phylogeny of a species in terms of vertical evolution, but instead represents the overall relatedness of genomes to one another and provide an assessment about the species genome evolution. Keywords: Comparative Genomic Hybridization
2009-09-09 | GSE8300 | GEO
Project description:We examined the Leishmania mexicana transcriptome to identify differentially regulated mRNAs using high-density whole-genome oligonucleotide microarrays designed from the genome data of a closely related species, Leishmania major. This experiment appears as Fig. 1 of the associated publication. Keywords: RNA expression profiling
2006-03-10 | GSE4430 | GEO
Project description:Hyaluronic acid (HA) is a biopolymer formed by UDP-glucuronic acid and UDP-N-acetyl-glucosamine disaccharide units linked by β-1,4 and β-1,3 glycosidic bonds. It is widely employed in medical and cosmetic procedures. HA is synthesized by hyaluronan synthase (HAS), which catalyzes the precursors' ligation in the cytosol, elongates the polymer chain, and exports it to the extracellular space. Here, we engineer Ogataea (Hansenula) polymorpha for HA production by inserting the genes encoding UDP-glucose 6-dehydrogenase, for UDP-glucuronic acid production, and HAS. Two microbial HAS, from Streptococcus zooepidemicus (hasAs) and Pasteurella multocida (hasAp), were evaluated separately. Additionally, we assessed a genetic switch using integrases in O. polymorpha to uncouple HA production from growth. Four strains were constructed containing both has genes under the control of different promoters. In the strain containing the genetic switch, HA production was verified by a capsule-like layer around the cells by scanning electron microscopy in the first 24 h of cultivation. For the other strains, the HA was quantified only after 48 h and in an optimized medium, indicating that HA production in O. polymorpha is limited by cultivation conditions. Nevertheless, these results provide a proof-of-principle that O. polymorpha is a suitable host for HA production.
| S-EPMC7913781 | biostudies-literature
Project description:Determine changes in genomic copy across the entire genome for isolated strains with selected gross chromosomal rearrangements relative to the wild-type strain.
2009-07-04 | E-TABM-714 | biostudies-arrayexpress
Project description:Haemophilus influenzae(Hi) is a gram-negative rod shaped bacterium that lives symbiotically in the upper respiratory tract of humans. Capsulated Hi, as well as non-capsulated strains are known to cause a number of significant infections. Recognizing and understanding the links between the phenotypic traits and the genetic background has paramount epidemiological and clinical importance. To date, a panoply of microbiological and molecular biology tools have been developed and utilized by researchers aimed at identifying the evolutionary links among strains and isolates. Comparative genomic hybridization (CGH) has been shown to be a useful tool for screening strains for their genetic content. However, there is a major limitation when CGH is conducted on a microarray based on a single reference genome. CGH results report which genes are present or absent relative to the genome. Hence the information about novel genetic content that the query strain possesses remains obscure. We report here the construction of the first Hi pan-genome microarray representing ca. 4600 features by 70-mers. In addition to those from the Rd strain, new features originate from the unfinished genome sequences present in NCBI database and from our novel gene discovery project efforts using strain HK1212. Genomes of 20strains belonging to different phylogenetic lineages were screened for their gene loss and gain utilizing the species microarray. The results obtained by employing the multistrain species microarray provide comprehensive information about the genomic content of uncharacterized strains. The trees generated by CGH, in general, do not reproduce the phylogeny of a species in terms of vertical evolution, but instead represents the overall relatedness of genomes to one another and provide an assessment about the species genome evolution. Keywords: Comparative Genomic Hybridization Twenty query strains (denoted HKxxxx) were investigated in this study, with each query strain hybridized against the reference strain, KW20. Two dye-swap experiments were performed, for a total of four hybridizations per query strain. Each 70mer oligo spotted on the H. influenzae species microarray is replicated six times. Positive controls on the array consist of oligos designed from the sequenced reference genome, KW20, and negative controls on the array consist of oligos designed from the thale cress plant, Arabidopsis thaliana.
2010-10-08 | E-GEOD-8300 | biostudies-arrayexpress
Project description:BackgroundOgataea polymorpha is a thermotolerant, methylotrophic yeast with significant industrial applications. While previously mainly used for protein synthesis, it also holds promise for producing platform chemicals. O. polymorpha has the distinct advantage of using methanol as a substrate, which could be potentially derived from carbon capture and utilization streams. Full development of the organism into a production strain and estimation of the metabolic capabilities require additional strain design, guided by metabolic modeling with a genome-scale metabolic model. However, to date, no genome-scale metabolic model is available for O. polymorpha.ResultsTo overcome this limitation, we used a published reconstruction of the closely related yeast Komagataella phaffii as a reference and corrected reactions based on KEGG and MGOB annotation. Additionally, we conducted phenotype microarray experiments to test the suitability of 190 substrates as carbon sources. Over three-quarter of the substrate use was correctly reproduced by the model and 27 new substrates were added, that were not present in the K. phaffii reference model.ConclusionThe developed genome-scale metabolic model of O. polymorpha will support the engineering of synthetic metabolic capabilities and enable the optimization of production processes, thereby supporting a sustainable future methanol economy.
| S-EPMC7962355 | biostudies-literature
Project description:Chromosomal rearrangements in N. gonorrhoeae and N. meningitidis were studied with the determination of mobile elements and their role in rearrangements. The results of whole-genome sequencing and de novo genome assembly for 50 N. gonorrhoeae isolates collected in Russia were compared with 96 genomes of N. gonorrhoeae and 138 genomes of N. meningitidis from the databases. Rearrangement events with the determination of the coordinates of syntenic blocks were analyzed using the SibeliaZ software v.1.2.5, the minimum number of events that allow one genome to pass into another was calculated using the DCJ-indel model using the UniMoG program v.1.0. Population-level analysis revealed a stronger correlation between changes in the gene order and phylogenetic proximity for N. meningitidis in contrast to N. gonorrhoeae. Mobile elements were identified, including Correa elements; Spencer-Smith elements (in N. gonorrhoeae); Neisserial intergenic mosaic elements; IS elements of IS5, IS30, IS110, IS1595 groups; Nf1-Nf3 prophages; NgoФ1-NgoФ9 prophages; and Mu-like prophages Pnm1, Pnm2, MuMenB (in N. meningitidis). More than 44% of the observed rearrangements most likely occurred with the participation of mobile elements, including prophages. No differences were found between the Russian and global N. gonorrhoeae population both in terms of rearrangement events and in the number of transposable elements in genomes.
| S-EPMC9778887 | biostudies-literature
Project description:A methylotrophic yeast important for industry
| PRJNA170212 | ENA
Project description:INTRODUCTION:Malignant pleural mesothelioma is a disease primarily associated with exposure to the carcinogen asbestos. Whereas other carcinogen-related tumors are associated with a high tumor mutation burden, mesothelioma is not. We sought to resolve this discrepancy. METHODS:We used mate-pair (n = 22), RNA (n = 28), and T cell receptor sequencing along with in silico predictions and immunologic assays to understand how structural variants of chromosomes affect the transcriptome. RESULTS:We observed that inter- or intrachromosomal rearrangements were present in every specimen and were frequently in a pattern of chromoanagenesis such as chromoplexy or chromothripsis. Transcription of rearrangement-related junctions was predicted to result in many potential neoantigens, some of which were proven to bind patient-specific major histocompatibility complex molecules and to expand intratumoral T cell clones. T cells responsive to these predicted neoantigens were also present in a patient's circulating T cell repertoire. Analysis of genomic array data from the mesothelioma cohort in The Cancer Genome Atlas suggested that multiple chromothriptic-like events negatively impact survival. CONCLUSIONS:Our findings represent the discovery of potential neoantigen expression driven by structural chromosomal rearrangements. These results may have implications for the development of novel immunotherapeutic strategies and the selection of patients to receive immunotherapies.
| S-EPMC6348045 | biostudies-literature