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PubMed2026

The cold case of state transition 7 (stt7) mutants of Chlamydomonas reinhardtii, solved by whole-genome sequencing.

The process of State Transitions (ST) corresponds to an STT7 kinase-driven redistribution of the transmembrane LHCII antenna proteins between Photosystem II (PSII) and Photosystem I (PSI), which results from changes in their phosphorylation state. For the past two decades, two LHCII-kinase mutants, stt7-1 and stt7-9, have been instrumental in the study of STs in Chlamydomonas reinhardtii, the former being a null mutant for the kinase but quasi-sterile in crosses, while the latter, although fertile, has a leaky phenotype. Using long-read sequencing, this study further characterized the genetic lesions of the stt7 mutant strains through whole-genome reconstruction and de novo chromosome assembly. In addition, two new stt7 null mutants were generated, one derived by crosses from the original stt7-1 and one obtained by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (Cas9) technology. This work provides a comprehensive genomic characterization of the original stt7-1 null mutant, revealing extensive chromosomal rearrangements and high levels of aneuploidy, associated with increased cell size and meiotic dysfunction. Reassessment of their physiology and genetic backgrounds highlights the need for caution in interpreting genetic information. We thus produced more reliable null mutants for the LHCII-kinase, amenable to genetic crosses for the study of STs in a variety of genetic backgrounds.

Chlamydomonas reinhardtii↗
PubMed2006

Genetic variation of populations of Citrus psorosis virus.

Citrus psorosis virus (CPsV), the type species of genus Ophiovirus, has a segmented, negative-stranded RNA genome. We examined the population structure and genetic variation of CPsV in three coding regions located in RNAs 1, 2 and 3, analysing 22 isolates from Argentina, California, Florida, Italy and Spain. Most isolates contained a predominant sequence and some minor variants. Estimations of the genetic diversity and phylogenetic clustering of isolates disclosed two populations, one comprising isolates from Spain, Italy, Florida and California and the other including the Argentinean isolates. Isolate CPV-4 (from Texas) included for comparison was distant from both groups, suggesting that it belongs to a third group. The low ratio between non-synonymous and synonymous nucleotide substitutions indicated strong selection for amino acid sequence conservation, particularly in the coat protein gene. Incongruent phylogenetic relationships in different genomic regions suggested that exchange of genomic segments may have contributed to CPsV evolution.

Genetic Variation↗
PubMed2001

Variations and constant patterns in eukaryotic MDR enzymes. Conclusions from novel structures and characterized genomes.

Medium-chain dehydrogenases/reductases (MDR) alcohol dehydrogenases exhibit multiple forms through a number of gene duplications. A crucial duplication was the one leading from the glutathione-dependent formaldehyde dehydrogenase line to the liver alcohol dehydrogenase (ADH) lines of vertebrates, the first duplication of which can now be further positioned at early vertebrate times. Similarly, screening of MDR forms in recently completed eukaryotic genomes of Caenorhabditis elegans and Drosophila melanogaster suggest that the MDR family may constitute a moderately sized protein family centered around a limited number of enzyme activities of five different structural types.

Alcohol Dehydrogenase↗
PubMed2024

Haplotype-resolved genome assembly and implementation of VitExpress, an open interactive transcriptomic platform for grapevine.

Haplotype-resolved genome assemblies were produced for Chasselas and Ugni Blanc, two heterozygous Vitis vinifera cultivars by combining high-fidelity long-read sequencing and high-throughput chromosome conformation capture (Hi-C). The telomere-to-telomere full coverage of the chromosomes allowed us to assemble separately the two haplo-genomes of both cultivars and revealed structural variations between the two haplotypes of a given cultivar. The deletions/insertions, inversions, translocations, and duplications provide insight into the evolutionary history and parental relationship among grape varieties. Integration of de novo single long-read sequencing of full-length transcript isoforms (Iso-Seq) yielded a highly improved genome annotation. Given its higher contiguity, and the robustness of the IsoSeq-based annotation, the Chasselas assembly meets the standard to become the annotated reference genome for V. vinifera. Building on these resources, we developed VitExpress, an open interactive transcriptomic platform, that provides a genome browser and integrated web tools for expression profiling, and a set of statistical tools (StatTools) for the identification of highly correlated genes. Implementation of the correlation finder tool for MybA1, a major regulator of the anthocyanin pathway, identified candidate genes associated with anthocyanin metabolism, whose expression patterns were experimentally validated as discriminating between black and white grapes. These resources and innovative tools for mining genome-related data are anticipated to foster advances in several areas of grapevine research.

Vitis↗
PubMed2005

Human subtelomere structure and variation.

Work towards completion of the human reference genome sequence has revealed a great deal of complexity and plasticity in human subtelomeric regions. The highly variable subtelomeric repeat regions are filled with recently shuffled genomic segments, many of which contain sequences matching transcripts and transcript fragments; the rapid duplication and combinatorial evolution of these regions has generated an extremely diverse set of subtelomeric alleles in the human species, the complexity and potential significance of which is only beginning to be understood. This review summarizes recent progress in analyzing human subtelomeric sequence assemblies and large-scale variation in human subtelomere regions.

Genetic Variation↗
PubMed2006

Genetic determinants of normal variation in coagulation factor (F) IX levels: genome-wide scan and examination of the FIX structural gene.

BACKGROUND: High-normal and elevated plasma FIX activity (FIX:C) levels are associated with increased risk for venous- and possibly arterial-thrombosis. OBJECTIVE: Because the broad normal range for FIX:C involves a substantial unknown genetic component, we sought to identify quantitative-trait loci (QTLs) for this medically important hemostasis trait. METHODS: We performed a genome-wide screen and a resequencing-based variation scan of the known functional regions of every distinct FIX gene (F9) in the genetic analysis of idiopathic thrombophilia project (GAIT), a collection of 398 Spanish-Caucasians from 21 pedigrees. RESULTS: We found no evidence for linkage (LOD scores <1.5) despite genotyping more than 540 uniformly-spaced microsatellites. We identified 27 candidate F9 polymorphisms, including three in cis-elements responsible for the increase in FIX:C that occurs with aging, but found no significant genotype-specific differences in mean FIX:C levels (P-values > or = 0.11) despite evaluating every polymorphism in GAIT by marginal multicovariate measured-genotype association analysis. CONCLUSIONS: The heritable component of interindividual FIX:C variability likely involves a collection of QTLs with modest effects that may reside in genes other than F9. Nevertheless, because the alleles of these 27 polymorphisms exhibited a low overall degree of linkage disequilibrium, we are currently defining their haplotypes to interrogate several highly-conserved non-exonic sequences and other F9 segments not examined here.

Adolescent↗
PubMed2005

Understanding ploidy complex and geographic origin of the Buchloe dactyloides genome using cytoplasmic and nuclear marker systems.

Characterizing and inferring the buffalograss [Buchloe dactyloides (Nutt.) Engelm.] genome organization and its relationship to geographic distribution are among the purposes of the buffalograss breeding and genetics program. This buffalograss study was initiated to: (1) better understand the buffalograss ploidy complex using various marker systems representing nuclear and organelle genomes; (2) determine whether the geographic distribution was related to nuclear and organelle genome variation; and (3) compare the genetic structure of accessions with different ploidy levels. The 20 buffalograss genotypes (15 individuals from each genotype) that were studied included diploid, tetraploid, pentaploid, and hexaploid using nuclear (intersimple sequence repeat (ISSRs), simple sequence repeat (SSRs), sequence related amplified polymorphism (SRAPs), and random amplified polymorphic DNA (RAPDs)) and cytoplasmic markers (mtDNA and cpDNA). There was a significant correlation between the ploidy levels and number of alleles detected using nuclear DNA (ISSR, SSR, and SRAP, r = 0.39, 0.39, and 0.41, P<0.05, respectively), but no significant correlation was detected when mitochondrial (r = 0.17, P<0.05) and chloroplast (r = 0.11, P < 0.05) DNA data sets were used. The geographic distribution of buffalograss was not correlated with nuclear and organelle genome variation for the genotypes studied. Among the total populations sampled, regression analysis indicated that geographic distance could not explain genetic differences between accessions. However, genetic distances of those populations from the southern portion of buffalograss adaptation were significantly correlated with geographic distance (r= 0.48, P<0.05). This result supports the hypothesis that genetic relationship among buffalograss populations cannot be estimated based only on geographic proximity.

DNA Primers↗
PubMed2024

Complete plastid genome of Iris orchioides and comparative analysis with 19 Iris plastomes.

Iris is a cosmopolitan genus comprising approximately 280 species distributed throughout the Northern Hemisphere. Although Iris is the most diverse group in the Iridaceae, the number of taxa is debatable owing to various taxonomic issues. Plastid genomes have been widely used for phylogenetic research in plants; however, only limited number of plastid DNA markers are available for phylogenetic study of the Iris. To understand the genomic features of plastids within the genus, including its structural and genetic variation, we newly sequenced and analyzed the complete plastid genome of I. orchioides and compared it with those of 19 other Iris taxa. Potential plastid markers for phylogenetic research were identified by computing the sequence divergence and phylogenetic informativeness. We then tested the utility of the markers with the phylogenies inferred from the markers and whole-plastome data. The average size of the plastid genome was 152,926 bp, and the overall genomic content and organization were nearly identical among the 20 Iris taxa, except for minor variations in the inverted repeats. We identified 10 highly informative regions (matK, ndhF, rpoC2, ycf1, ycf2, rps15-ycf, rpoB-trnC, petA-psbJ, ndhG-ndhI and psbK-trnQ) and inferred a phylogeny from each region individually, as well as from their concatenated data. Remarkably, the phylogeny reconstructed from the concatenated data comprising three selected regions (rpoC2, ycf1 and ycf2) exhibited the highest congruence with the phylogeny derived from the entire plastome dataset. The result suggests that this subset of data could serve as a viable alternative to the complete plastome data, especially for molecular diagnoses among closely related Iris taxa, and at a lower cost.

Iris Plant↗
PubMed2000

Adjusting the focus on human variation.

Studies of nuclear sequence variation are accumulating, such that we can expect a good description of the structure of human variation across populations and genomic regions in the near future. This description will help to elucidate the evolutionary forces that shape patterns of variability. Such an understanding will be of general biological interest, but could also facilitate the design and interpretation of disease-mapping studies. Here, we integrate the results from surveys of nuclear sequence variation. When nuclear sequences are considered together with mtDNA and microsatellites, it becomes clear that neither the standard neutral model, nor a simple long-term exponential growth model, can account for all the available human variation data. A possible explanation is that a subset of loci are not evolving neutrally; even so, more-complex models of effective population size and structure might be necessary to explain the data.

Biological Evolution↗
PubMed2006

Carotenoid biosynthesis in cyanobacteria: structural and evolutionary scenarios based on comparative genomics.

Carotenoids are widely distributed pigments in nature and their biosynthetic pathway has been extensively studied in various organisms. The recent access to the overwhelming amount genomic data of cyanobacteria has given birth to a novel approach called comparative genomics. The putative enzymes involved in the carotenoid biosynthesis among the cyanobacteria were determined by similarity-based tools. The reconstruction of biosynthetic pathway was based on the related enzymes. It is interesting to find that nearly all the cyanobacteria share quite similar pathway to synthesize beta-carotene except for Gloeobacter violaceus PCC 7421. The enzymes, crtE-B-P-Qb-L, involved in the upstream pathway are more conserved than the subsequent ones (crtW-R). In addition, many carotenoid synthesis enzymes exhibit diversity in structure and function. Such examples in the families of zeta -carotene desaturase, lycopene cylases and carotene ketolases were described in this article. When we mapped these crt genes to the cyanobacterial genomes, the crt genes showed great structural variation among species. All of them are dispersed on the whole chromosome in contrast to the linear adjacent distribution of the crt gene cluster in other eubacteria. Moreover, in unicellular cyanobacteria, each step of the carotenogenic pathway is usually catalyzed by one gene product, whereas multiple ketolase genes are found in filamentous cyanobacteria. Such increased numbers of crt genes and their correlation to the ecological adaptation were carefully discussed.

Bacteria↗
PubMed2001

Molecular characterization of two natural hotspots in the Drosophila buzzatii genome induced by transposon insertions.

Transposable elements (TEs) have been implicated in the generation of genetic rearrangements, but their potential to mediate changes in the organization and architecture of host genomes could be even greater than previously thought. Here, we describe the naturally occurring structural and nucleotide variation around two TE insertions in the genome of Drosophila buzzatii. The studied regions correspond to the breakpoints of a widespread chromosomal inversion generated by ectopic recombination between oppositely oriented copies of a TE named Galileo. A detailed molecular analysis by Southern hybridization, PCR amplification, and DNA sequencing of 7.1 kb surrounding the inversion breakpoints in 39 D. buzzatii lines revealed an unprecedented degree of restructuring, consisting of 22 insertions of ten previously undescribed TEs, 13 deletions, 1 duplication, and 1 small inversion. All of these alterations occurred exclusively in inverted chromosomes and appear to have accumulated after the insertion of the Galileo elements, within or close to them. The nucleotide variation at the studied regions is six times lower in inverted than in noninverted chromosomes, suggesting that most of the observed changes originated in only 84,000 years. Galileo elements thus seemed to promote the transformation of these, otherwise normal, chromosomal regions in genetically unstable hotspots and highly efficient traps for transposon insertions. The particular features of two new Galileo copies found indicate that this TE belongs to the Foldback family. Together, our results strengthen the importance of TEs, and especially DNA transposons, as inducers of genome plasticity in evolution.

Animals↗
PubMed2001

Genetic variation in the human urea transporter-2 is associated with variation in blood pressure.

The kidney, by regulating the volume of fluid in the body, plays a key role in regulating blood pressure (BP). The kidney uses primarily sodium and, to a lesser extent, urea to maintain the appropriate volume of fluid. Genetic variation in proteins that determine sodium reabsorption and excretion is known to significantly influence BP. However, the influence of genetic variation in urea transporters on BP has not been examined. We determined therefore whether nucleotide variation in the kidney-specific human urea transporter, HUT2, is associated with variation in BP. After determining the genomic structure of the coding sequence, seven single nucleotide polymorphisms (SNPs) were identified. Two of the SNPs result in Val/Ile and Ala/Thr amino acid substitutions at positions 227 and 357 in the HUT2 open reading frame, respectively. Another SNP is silent and four others are in introns or the 3' untranslated region. Over 1000 hypertensive and low-normotensive individuals of Chinese origin were typed for five of these SNPs using a high-throughput genotyping method. The Ile227 and Ala357 alleles were associated with low diastolic BP in men but not women, with odds ratios 2.1 [95% confidence interval (CI) 1.5-2.7, P < 0.001] and 1.5 (95% CI 1.2-1.8, P < 0.001), respectively. There was a similar trend for systolic BP, and odds ratios for the Ile227 and Ala357 alleles were 1.7 (95% CI 1.2-2.3, P = 0.002) and 1.3 (95% CI 1.1-1.6, P = 0.007), respectively, in men.

Blood Pressure↗
PubMed2003

Characterization of the structure and variability of an internal region of hepatitis C virus RNA for M1 RNA guide sequence ribozyme targeting.

Accessibility to folded RNA and low potential of variation in the target RNA are crucial requirements for ribozyme therapy against virus infections. In hepatitis C virus (HCV), the sequence of the 5'UTR is conserved but the highly folded RNA structure severely limits the number of accessible sites. To expand investigation of targeting in the HCV genome, we have considered an internal genomic region whose sequence variation has been widely investigated and which has a particularly conserved RNA structure, which makes it accessible to the human RNase P in vitro. We have first mapped the accessibility of the genomic RNA to complementary DNAs within this internal genomic region. We performed a kinetic and thermodynamic study. Accordingly, we have designed and assayed four RNase P M1 RNA guide sequence ribozymes targeted to the selected sites. Considerations of RNA structural accessibility and sequence variation indicate that several target sites should be defined for simultaneous attack.

Base Sequence↗
PubMed1998

Variation in genome organization of the plant pathogenic fungus Colletotrichum lindemuthianum.

The genome structure of Colletotrichum lindemuthianum in a set of diverse isolates was investigated using a combination of physical and molecular approaches. Flow cytometric measurement of genome size revealed significant variation between strains, with the smallest genome representing 59% of the largest. Southern-blot profiles of a cloned fungal telomere revealed a total chromosome number varying from 9 to 12. Chromosome separations using pulsed-field gel electrophoresis (PFGE) showed that these chromosomes belong to two distinct size classes: a variable number of small (< 2.5 Mb) polymorphic chromosomes and a set of unresolved chromosomes larger than 7 Mb. Two dispersed repeat elements were shown to cluster on distinct polymorphic minichromosomes. Single-copy flanking sequences from these repeat-containing clones specifically marked distinct small chromosomes. These markers were absent in some strains, indicating that part of the observed variability in genome organization may be explained by the presence or absence, in a given strain, of dispensable genomic regions and/or chromosomes.

Ascomycota↗
PubMed2024

Diversity of ribosomes at the level of rRNA variation associated with human health and disease.

With hundreds of copies of rDNA, it is unknown whether they possess sequence variations that form different types of ribosomes. Here, we developed an algorithm for long-read variant calling, termed RGA, which revealed that variations in human rDNA loci are predominantly insertion-deletion (indel) variants. We developed full-length rRNA sequencing (RIBO-RT) and in situ sequencing (SWITCH-seq), which showed that translating ribosomes possess variation in rRNA. Over 1,000 variants are lowly expressed. However, tens of variants are abundant and form distinct rRNA subtypes with different structures near indels as revealed by long-read rRNA structure probing coupled to dimethyl sulfate sequencing. rRNA subtypes show differential expression in endoderm/ectoderm-derived tissues, and in cancer, low-abundance rRNA variants can become highly expressed. Together, this study identifies the diversity of ribosomes at the level of rRNA variants, their chromosomal location, and unique structure as well as the association of ribosome variation with tissue-specific biology and cancer.

Humans↗
PubMed2026

Ancient DNA and Human Physiology.

Ancient DNA (aDNA) enables the reconstruction of chronologically sampled genomes from ancient humans, animals, plants, pathogens, and microorganisms, as well as environmental DNA, providing a record of biological changes through time. Improvements in short and degraded DNA extraction methods and low-cost sequencing now enable the generation of broad, cross-regional datasets that expand evolutionary analyses from past population demography to biological mechanisms. By tracking temporal shifts of allele frequencies, integrating functional genomics resources (e.g., gene expression, chromatin structure variation), modeling population demography to separate selection from genetic drift, and aligning genetic changes with archaeological, cultural, and climatic data, aDNA has the potential to link sequence variation to physiological function within their temporal and environmental contexts. In this review, we summarize illustrative case studies from aDNA research spanning complex traits, dietary adaptations, and responses to pathogens and other environmental changes, showing how human biology has evolved under multiple selective pressures through time. These dated signals help triage experimental work and expose mechanisms that are rare or absent in living cohorts. Although some challenges remain, such as geographic and temporal sampling disparities, limitations in data resolution and variant detection, and genotype-phenotype uncertainties, rapid methodological progress and stronger ethical frameworks are expanding what can be inferred, making aDNA a promising tool for refining physiological pathways, their timing, and their drivers.

Humans↗
PubMed2001

Molecular cloning and phylogenetic analysis of the human endogenous retrovirus HERV-K long terminal repeat elements in various cancer cells.

Long terminal repeats (LTRs) of the human endogenous retroviruses K family (HERV-K) have been found to affect expression of genes located nearby. It has been suggested that the HERV-K LTR elements contributed to the structural change in the genome and genetic variation connected to various diseases. We examined the HERV-K LTR elements in human cancer cells. Using genomic DNA from various cancer cells, we performed PCR amplification and identified forty-nine HERV-K LTR elements. Those LTR elements showed a high degree of sequence similarity with human-specific HERV-K LTR elements. A phylogenetic tree, obtained by the neighbor-joining method, revealed that twelve HERV-K LTR elements were closely related to human-specific HERV-K LTR elements. These elements proliferated recently and were detectable in many human cancer cell lines. These results suggest that HERV-K LTR could be implicated in a pathogenic role, although this phenomenon may not directly lead to human cancers. Further studies on the biological function and expression of HERV-K LTR elements in cancer cells are indicated.

Cloning, Molecular↗
PubMed2003

Molecular phylogeny and evolution of the human endogenous retrovirus HERV-W LTR family in hominoid primates.

Long terminal repeats (LTRs) of human endogenous retrovirus (HERV) have contributed to the structural change or genetic variation of primate genome that are connected to speciation and evolution. Using genomic DNAs that were derived from hominoid primates (chimpanzee, gorilla, orangutan, and gibbon), we performed PCR amplification and identified thirty HERV-W LTR elements. These LTR elements showed a 82-98% sequence similarity with HERV-W LTR (AF072500). Specifically, additional sequences (GCCACCACCACTGTTT in the gorilla and TGCTGCTGACTCCCATCC in the gibbon) were noticed. Clone OR3 from the orangutan and clone GI2 from the gibbon showed a 100% sequence similarity, although they are different species. This indicates that both LTR elements were proliferated during the last 2 to 5 million years from the integration of the original LTR element. A phylogenetic tree that was obtained by the neighbor-joining method revealed a wide overlap of the LTR elements across species, suggesting that the HERV-W LTR family evolved independently during the hominoid evolution.

Amino Acid Sequence↗