scholarly journals Gene Family Complexity and Expression Divergence as a Mechanism of Adaptation In Coral

2021 ◽  
Author(s):  
Bradford Dimos ◽  
Madison Emery ◽  
Nicholas MacKnight ◽  
Marilyn Brandt ◽  
Jeffery Demuth ◽  
...  
Keyword(s):  
Gene Family ◽  
Gene Dosage ◽  
Genetic Material ◽  
Gene Copy Number ◽  
Empirical Support ◽  
Gene Copy ◽  
Expression Divergence ◽  
Immune Genes ◽  
Natural Systems ◽  
Family Complexity

AbstractGene family complexity and its influence on expression dynamics has long been theorized to be an important source of adaptation in natural systems through providing novel genetic material and influencing gene dosage. There is now growing empirical support for this theory; however, this process has only been demonstrated in a limited number of systems typically using recently diverged species or populations. In particular, examples of how this process operates in basal animals with deeper species splits has not been well explored. To address this issue, we investigated the evolution of gene family complexity in five species of common Caribbean coral. We demonstrate widespread divergence in gene repertoires owing to slow rates of gene turnover occurring along deep species splits. The resulting differences in gene family complexity involve numerous biologic processes, shedding light on to the selective forces that have influenced the evolution of each species. By coupling these findings with gene expression data, we show that increased gene family complexity promotes increased expression divergence between species, indicating an interplay between gene family complexity and expression divergence. Finally, we show that immune genes are evolving particularly fast demonstrating the importance of interactions with other organisms in the evolutionary history of Caribbean corals. Overall, these findings provide support for gene copy number change as an important evolutionary force in Caribbean corals, which may influence their ability to persist in a rapidly changing environment.

Gene Expression Profiling of Hyperdiploid Multiple Reveal Complex Gene Dosage Effects and an mRNA Translation/Protein Synthesis Signature.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1538-1538
Author(s):  
Wee-Joo Chng ◽  
Scott Van Wier ◽  
Gregory Ahmann ◽  
Tammy Price-Troska ◽  
Kim Henderson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Differentially Expressed Genes ◽  
Gene Dosage ◽  
Gene Copy Number ◽  
Mrna Translation ◽  
Differentially Expressed ◽  
Gene Copy ◽  
Gene Dosage Effect ◽  
Expression Of Genes

Abstract Hyperdiploid MM (H-MM), characterized by recurrent trisomies constitute about 50% of MM, yet very little is known about its pathogenesis and oncogenic mechanisms. Studies in leukemia and solid tumors have shown gene dosage effect of aneuploidy on gene expression. To determine the possible gene dosage effect and deregulated cellular program in H-MM we undertook a gene expression study of CD138-enriched plasma-cell RNA from 53 hyperdiploid and 37 non-hyperdiploid MM (NH-MM) patients using the Affymetrix U133A chip (Affymetrix, Santa Clara, CA). Gene expression data was analyzed using GeneSpring 7 (Agilent Technologies, Palo Alto, CA). Genes differentially expressed between H-MM and NH-MM were obtained by t-test (p<0.01). The majority of the differentially expressed genes (57%) were under-expressed in H-MM. Genes located on the commonly trisomic chromosomes were mostly (but not always) over-expressed in H-MM and constitute 76% of over-expressed genes. Chromosome 1 contained the most differentially expressed genes (17%) followed by chromosome 12 (9%), and 19 (8%). To examine the relationship of gene copy number to gene expression, we examined the expression of genes on chromosomes 9 and 15 in subjects with 2 copies (15 normal control and 20 NH-MM) and 3 copies (12 H-MM) of each chromosome as detected by interphase FISH. We then derived a ratio of the mean expression of each gene on these chromosomes between patients with 3 copies and 2 copies of the chromosome. If a simple relationship exists between gene expression and gene copy number, one would expect the ratio of expression of most genes on these two chromosomes to be about 1.5 in H-MM compared to NH-MM. However, many genes have ratios either higher than 2 or lower than 0.5. Furthermore, when the heterogeneity of cells with underlying trisomies is taken into consideration by correcting the ratio for the number of cells with trisomies, the actual ratio is always lower than the expected ratio. When the expression of genes on a chromosome was compressed to a median value, this value was always higher in the trisomic chromosomes for H-MM compared to NH-MM. The data suggests that although gene dosage influence gene expression, the relationship is complex and some genes are more gene dosage dependent than others. Amongst the differentially expressed genes with known function, 33% are involved in mRNA translation/protein synthesis. Of note, 37 of the top 100 differentially expressed genes are involved in these processes. In particular, 60 ribosomal protein (RP) genes are significantly (p<0.05) upregulated in H-MM. This signature in H-MM is not associated with increase proliferation as measured by PCLI. This predominant signature suggests that deregulated protein synthesis may be important for the biology of H-MM. Many of these RPs are involved in the synthesis of product of oncogenic pathways (e.g. MYC, NF-KB pathways) and may mediate the growth and survival of tumor cells. It is therefore possible that these tumor cells may be sensitive to the disruption of mRNA translation/protein synthesis. Targeting the mTOR pathway with rapamycin may therefore be useful for treatment of H-MM.

scholarly journals Rapid Real-Time Fluorescent PCR Gene Dosage Test for the Diagnosis of DNA Duplications and Deletions

2000 ◽  
Vol 46 (10) ◽  
pp. 1574-1582 ◽  
Author(s):  
Clara Ruiz-Ponte ◽  
Lourdes Loidi ◽  
Ana Vega ◽  
Angel Carracedo ◽  
Francisco Barros
Keyword(s):  
Real Time ◽  
Capillary Tube ◽  
Gene Dosage ◽  
Melting Curve ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Target Sequence ◽  
Hereditary Neuropathy ◽  
Target Dna ◽  
Fluorescent Pcr

Abstract Background: Current methods to determine gene dosage are time-consuming and labor-intensive. We describe a new and rapid method to assess gene copy number for identification of DNA duplications or deletions occurring in Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP), respectively. Methods: We studied 16 patients with HNPP, 4 with CMT1A, and 49 control subjects. We used real-time PCR on the LightCycler system with use of a single capillary tube and no post-PCR handling. A polymorphic fragment of the PMP22 gene was amplified to determine gene dosage for heterozygous samples. The presence of two alleles was used to indicate that no deletion was present in HNPP samples. The ratio obtained between the areas under each allele melting curve of heterozygous CMT1A samples was used to determine whether the sequence was duplicated or normal. Homozygous samples required a competitive gene dosage test, where the ratio between the areas under the melting curves of the target DNA of samples and of the competitor molecule was used to determine whether the target sequence was duplicated, deleted, or normal. Samples from HNPP, CMT1A, and controls were analyzed. Results: Area ratios were ∼0.6, 1.0, and 2.0 for HNPP, control, and CMT1A samples, respectively. The results agreed with those obtained by Southern blotting and microsatellite analysis in the same samples. Conclusions: Direct and competitive real-time fluorescent PCR can differentiate one, two, or three copies of the target DNA. The method described is sensitive and accurate for detection of CMT1A duplications and HNPP deletions and is faster and easier than current methods.

scholarly journals Genome instability drives epistatic adaptation in the human pathogen Leishmania

2021 ◽  
Vol 118 (51) ◽  
pp. e2113744118
Author(s):  
Giovanni Bussotti ◽  
Laura Piel ◽  
Pascale Pescher ◽  
Malgorzata A. Domagalska ◽  
K. Shanmugha Rajan ◽  
...  
Keyword(s):  
Translational Control ◽  
Copy Number ◽  
Biomarker Discovery ◽  
Genome Instability ◽  
Gene Dosage ◽  
Gene Copy Number ◽  
Copy Number Variations ◽  
Gene Copy ◽  
Snorna Gene ◽  
Ideal System

How genome instability is harnessed for fitness gain despite its potential deleterious effects is largely elusive. An ideal system to address this important open question is provided by the protozoan pathogen Leishmania, which exploits frequent variations in chromosome and gene copy number to regulate expression levels. Using ecological genomics and experimental evolution approaches, we provide evidence that Leishmania adaptation relies on epistatic interactions between functionally associated gene copy number variations in pathways driving fitness gain in a given environment. We further uncover posttranscriptional regulation as a key mechanism that compensates for deleterious gene dosage effects and provides phenotypic robustness to genetically heterogenous parasite populations. Finally, we correlate dynamic variations in small nucleolar RNA (snoRNA) gene dosage with changes in ribosomal RNA 2′-O-methylation and pseudouridylation, suggesting translational control as an additional layer of parasite adaptation. Leishmania genome instability is thus harnessed for fitness gain by genome-dependent variations in gene expression and genome-independent compensatory mechanisms. This allows for polyclonal adaptation and maintenance of genetic heterogeneity despite strong selective pressure. The epistatic adaptation described here needs to be considered in Leishmania epidemiology and biomarker discovery and may be relevant to other fast-evolving eukaryotic cells that exploit genome instability for adaptation, such as fungal pathogens or cancer.

scholarly journals Genome plasticity in Paramecium bursaria revealed by population genomics

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Yu-Hsuan Cheng ◽  
Chien-Fu Jeff Liu ◽  
Yen-Hsin Yu ◽  
Yu-Ting Jhou ◽  
Masahiro Fujishima ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Population Genomics ◽  
Gene Dosage ◽  
Gene Copy Number ◽  
Paramecium Bursaria ◽  
Gene Copy ◽  
Genome Plasticity ◽  
Ciliate Species ◽  
Number Variation

Abstract Background Ciliates are an ancient and diverse eukaryotic group found in various environments. A unique feature of ciliates is their nuclear dimorphism, by which two types of nuclei, the diploid germline micronucleus (MIC) and polyploidy somatic macronucleus (MAC), are present in the same cytoplasm and serve different functions. During each sexual cycle, ciliates develop a new macronucleus in which newly fused genomes are extensively rearranged to generate functional minichromosomes. Interestingly, each ciliate species seems to have its way of processing genomes, providing a diversity of resources for studying genome plasticity and its regulation. Here, we sequenced and analyzed the macronuclear genome of different strains of Paramecium bursaria, a highly divergent species of the genus Paramecium which can stably establish endosymbioses with green algae. Results We assembled a high-quality macronuclear genome of P. bursaria and further refined genome annotation by comparing population genomic data. We identified several species-specific expansions in protein families and gene lineages that are potentially associated with endosymbiosis. Moreover, we observed an intensive chromosome breakage pattern that occurred during or shortly after sexual reproduction and contributed to highly variable gene dosage throughout the genome. However, patterns of copy number variation were highly correlated among genetically divergent strains, suggesting that copy number is adjusted by some regulatory mechanisms or natural selection. Further analysis showed that genes with low copy number variation among populations tended to function in basic cellular pathways, whereas highly variable genes were enriched in environmental response pathways. Conclusions We report programmed DNA rearrangements in the P. bursaria macronuclear genome that allow cells to adjust gene copy number globally according to individual gene functions. Our results suggest that large-scale gene copy number variation may represent an ancient mechanism for cells to adapt to different environments.

scholarly journals Genome location dictates the transcriptional response to PolC-inhibition inClostridium difficile

2018 ◽  
Author(s):  
Erika van Eijk ◽  
Ilse M. Boekhoud ◽  
Ed J. Kuijper ◽  
Ingrid M.J.G. Bos-Sanders ◽  
George Wright ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Gene Dosage ◽  
Response Regulator ◽  
Treatment Options ◽  
Gene Copy Number ◽  
Transcriptional Response ◽  
Current Treatment ◽  
Gene Copy ◽  
Growth Defect

AbstractClostridium difficileis a potentially lethal gut pathogen that causes nosocomial and community acquired infections. Limited treatment options and reports of reduced susceptibility to current treatment emphasize the necessity for novel antimicrobials. The DNA-polymerase of gram-positive organisms is an attractive target for the development of antimicrobials. ACX-362E (N2-(3<,4-Dichlorobenzyl)-7-(2-[1-morpholinyl]ethyl)guanine; MorE-DCBG) is a DNA polymerase inhibitor in pre-clinical development as a novel therapeutic againstC. difficileinfection. This synthetic purine shows preferential activity againstC. difficilePolC over those of other organismsin vitroand is effective in an animal model ofC. difficileinfection. In this study we have determined its efficacy against a large collection of clinical isolates. At concentrations below the minimal inhibitory concentration, the presumed slowing (or stalling) of replication forks due to ACX-362E leads to a growth defect. We have determined the transcriptional response ofC. difficileto replication inhibition and observed an overrepresentation of up-regulated genes near the origin of replication in the presence of PolC-inhibitors, but not when cells were subjected to sub-inhibitory concentrations of other antibiotics. This phenomenon can be explained by a gene dosage shift, as we observed a concomitant increase in the ratio between origin-proximal versus terminus-proximal gene copy number upon exposure to PolC-inhibitors. Moreover, we show that certain genes differentially regulated under PolC-inhibition are controlled by the origin-proximal general stress response regulator sigma factor B. Together, these data suggest that genome location both directly and indirectly determines the transcriptional response to replication inhibition inC. difficile.

scholarly journals Histidine Operon Deattenuation in dnaAMutants of Salmonella typhimurium Correlates with a Decrease in the Gene Dosage Ratio between tRNAHis and Histidine Biosynthetic Loci

1999 ◽  
Vol 181 (9) ◽  
pp. 2938-2941 ◽  
Author(s):  
Anne-Beatrice Blanc-Potard ◽  
Nara Figueroa-Bossi ◽  
Lionello Bossi
Keyword(s):  
Salmonella Typhimurium ◽  
Copy Number ◽  
Gene Dosage ◽  
Gene Copy Number ◽  
Gene Copy

ABSTRACT Expression of the histidine operon of Salmonella typhimurium is increased in dnaA(Ts) mutants at 37°C. This effect requires an intact his attenuator and can be suppressed by increasing the gene copy number of thehisR locus, which encodes the tRNAHis. We present data which suggest that the his deattenuation defect in dnaA(Ts) mutants results from the loss of a gene dosage gradient between the hisR locus, close tooriC, and the his operon, far fromoriC. Some of the conclusions drawn here may apply to other operons as well.

scholarly journals Determination of Cytochrome P450 2D6 (CYP2D6) Gene Copy Number by Real-Time Quantitative PCR

2005 ◽  
Vol 2005 (3) ◽  
pp. 248-253 ◽  
Author(s):  
Laurent Bodin ◽  
Philippe H. Beaune ◽  
Marie-Anne Loriot
Keyword(s):  
Real Time ◽  
Quantitative Pcr ◽  
Copy Number ◽  
Gene Dosage ◽  
Gene Copy Number ◽  
Rapid Identification ◽  
Gene Copy ◽  
Cyp2d6 Gene ◽  
Real Time Quantitative Pcr ◽  
Gene Copies

Gene dosage by real-time quantitative PCR has proved to be accurate for measuring gene copy number. The aim of this study was to apply this approach to the CYP2D6 gene to allow for rapid identification of poor and ultrarapid metabolizers (0, 1, or more than 2 gene copy number). Using the2−ΔΔCtcalculation method and a duplex reaction, the number of CYP2D6 gene copies was determined. Quantitative PCR was performed on 43 samples previously analyzed by Southern blotting and long PCR including 20 samples with a heterozygous deletion, 11 with normal copy number (2 copies), and 12 samples with duplicated genes. The average ratio ranged from1.02to1.28,1.85to2.21, and2.55to3.30, respectively, for the samples with 1 copy, 2 copies, and 3 copies. This study shows that this method is sensitive enough to detect either a heterozygous gene deletion or duplication.

Population differences in antifreeze protein gene copy number and arrangement in winter flounder

Genome ◽  
1991 ◽  
Vol 34 (1) ◽  
pp. 174-177 ◽  
Author(s):  
Pliny H. Hayes ◽  
Peter L. Davies ◽  
Garth L. Fletcher
Keyword(s):  
Multigene Family ◽  
Copy Number ◽  
Tandem Repeats ◽  
Freezing Point ◽  
Gene Dosage ◽  
Gene Copy Number ◽  
Gene Organization ◽  
Winter Flounder ◽  
Gene Copy ◽  
Intrapopulation Variation

Many marine fish in polar waters produce antifreeze proteins (AFPs) to depress their serum freezing point to below that of seawater. Winter flounder from the east coast of North America contain multiple AFP gene copies organized both as tandem repeats and as linked but irregularly spaced genes, with the tandemly repeated genes encoding the bulk of the circulating AFPs. We report here on AFP gene organization in winter flounder from nine locations ranging from Long Island, NY to Conception Bay, Nfld. There are clear differences in AFP gene copy number and arrangement between some of the populations. The greatest variation is seen in the size of the tandem component in fish from the warmer, deeper locations. This contrasts to the conservation of organization in the dispersed, β-tubulin multigene family used for comparative purposes. We suggest that variation in AFP gene family size and organization reflects a relaxation of selection in some geographical areas in the postglacial period.Key words: gene dosage, multigene family, tandem repeats, intrapopulation variation, glaciation.

scholarly journals Aneuploidy influences the gene expression profiles in Saccharomyces pastorianus group I and II strains during fermentation.

2021 ◽  
Author(s):  
Roberto de la Cerda ◽  
Karsten Hookamp ◽  
Fiona Roche ◽  
Georgia Thompson ◽  
Soukaina Timouma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
Gene Dosage ◽  
Expression Patterns ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Gene Expression Patterns ◽  
Group I ◽  
Saccharomyces Pastorianus ◽  
Group Ii

The lager yeasts, Saccharomyces pastorianus, are hybrids of Saccharomyces cerevisiae and Saccharomyces eubayanus and are divided into two broad groups, Group I and II. The two groups evolved from at least one common hybridisation event but have subsequently diverged with Group I strains losing many S. cerevisiae chromosomes while the Group II strains retain both sub-genomes. The complex genomes, containing orthologous alleles from the parental chromosomes, pose interesting questions regarding gene regulation and its impact on the fermentation properties of the strains. Superimposed on the presence of orthologous alleles are complexities of gene dosage due to the aneuploid nature of the genomes. We examined the contribution of the S. cerevisiae and S. eubayanus alleles to the gene expression patterns of Group I and II strains during fermentation. We show that the relative expression of S. cerevisiae and S. eubayanus orthologues is positively correlated with gene copy number. Despite the reduced S. cerevisiae content in the Group I strain, S. cerevisiae orthologues contribute to biochemical pathways upregulated during fermentation which may explain the retention of specific chromosomes in the strain. Conversely, S. eubayanus genes are significantly overrepresented in the upregulated gene pool in the Group II strain. Comparison of the transcription profiles of Group I and II strains during fermentation identified both common and unique gene expression patterns, with gene copy number being a dominant contributory factor. Thus, the aneuploid genomes create complex patterns of gene expression during fermentation with gene dosage playing a crucial role both within and between strains.

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