Natural variation in the blood--brain barrier.
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The NgoII restriction-modification (R-M) system of Neisseria gonorrhoeae recognizes the sequence 5'-GGCC-3'. This system is encoded by two separate genes, dcmB for the methyltransferase (MTase) and dcrB for the restriction endonuclease (ENase). Three strains that vary in their NgoII phenotype were examined. Strain Pgh3-2 produced detectable levels of both enzymes, strain F62 lacked detectable levels of the dcrB gene product, and strain WR302 failed to produce either gene product. Strains that lacked either enzyme activity still possessed the genes that encode them. Transcriptional fusions of dcrB in strains F62 and Pgh3-2 indicate that this gene is transcribed at nearly identical levels in each strain. The DNA encoding the NgoII R-M system was cloned from the three strains, and the nucleotide sequence was determined. The dcrB genes of WR302 and F62 possess the same frameshift mutation (base position 1435) which would result in a truncated protein. The WR302 dcmB was found to have a point mutation that changed Arg288 (a residue that is conserved in all prokaryotic and phage cytosine MTases sequenced to date) to Trp.
Concentrations of a metallothionein-like protein (MTLP) in Tubifex tubifex were consistent throughout the various life stages with no significant variation associated with reproductive stage. The mean concentration from cocoon through 10 weeks of age was 2.5 (+/-0.6) nmol MTLP/g. T. tubifex was subjected to a number of potential environmental stressors to determine whether MTLP production could be induced in the absence of metal exposure. There were no significant differences in the concentrations of MTLP between the controls and worms subjected to decreased food supply, increased handling, or reduced dissolved oxygen at a given exposure temperature. However, at 12 degrees C T. tubifex had significantly (P < 0.01) higher MTLP than T. tubifex held at 23 degrees C. There were also significant differences in wet weight and reproduction at the two temperatures, which may have implications for the levels of MTLP.
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Fusarium verticillioides and other Fusarium species were examined for their spore germination phenotypes. In general, germinating spores of F. verticillioides formed germ tubes that immediately penetrated into agar. Such invasive germination was the predominant growth phenotype among 22 examined field isolates of F. verticillioides from a broad range hosts and locations. However, two of the field isolates were unique in that they formed conidial germ tubes and hyphae that grew along the surface of agar before penetration eventually occurred. Conidia of 22 other Fusarium species were assessed for their germination phenotypes, and only some strains of F. annulatum, F. fujikuroi, F. globosum, F. nygamai, and F. pseudoanthophilum had the surface germination phenotype (21% of the strains assessed). Sexual crosses and segregation analyses involving one of the F. verticillioides surface germination strains, NRRL 25059, indicated a single locus, designated SIG1 (surface vs. invasive germination), controlled the germ tube growth phenotypes exhibited by both conidia and ascospores. Perfect correlation was observed between an ascospore germination phenotype and the germination phenotype of the conidia produced from the resulting ascospore-derived colony. Recombination data suggested SIG1 was linked ( approximately 7% recombination frequency) to FPH1, a recently described locus necessary for enteroblastic conidiogenesis. Corn seedling blight assays indicated surface germinating strains of F. verticillioides were less virulent than invasively germinating strains. Assays also indicated pathogenicity segregated independently of the FPH1 locus. Invasive germination is proposed as the dominant form of spore germination among Fusarium species. Furthermore, conidia were not necessary for corn seedling disease development, but invasive germination may have enhanced the virulence of conidiating strains.
Electrophoresis of Drosophila microsomes resolves two major heme-containing protein bands with apparent molecular weights of 59,290 (band a) and 55,750 (band b). The hemoproteins in these two bands can account for most of the cytochrome P-450 in the organism. Band a is present in all strains examined: band b is not. Dimethylnitrosamine demethylase, a P-450 enzyme, is a component of band b.
Prostaglandins E, F, 19-hydroxy E, and 19-hydroxy F (PGE, PGF, 19-OH-PGE, and 19-OH-PGF) in human semen were determined by a new chemical method. The method allows liquefaction to occur, a prerequisite for simultaneous estimation of PG concentration and sperm characteristics in the same ejaculate. The present study showed also that the variation in PG concentration between different individuals was more pronounced than in repeated ejaculates from the same individual. Sperm density and sperm motility seemed related to PG concentration. A high density was associated with a low PG concentration. The concentration of 19-OH-PGE was higher and that of 19-OH-PGF lower in ejaculates with a normal sperm motility than in those with an abnormal motility. It seems that functional requisites of sperm depend upon optimal seminal PG concentration.
This study identifies genetic loci affecting femoral bone length and width measures in mature mice. Sixteen month old female F2 progeny of a C57BL/6J and DBA/2J intercross were examined for femur length and width of the femoral head, intertrochanteric region and three locations of the diaphysis using digitized images of femur radiographs obtained in the anterior-posterior and lateral projections. A genome wide linkage map was constructed using microsatellite markers at an average density of 20 cM, and quantitative trait locus analysis used to identify regions of the genome showing linkage with the traits measured. Femur length showed significant linkage with loci on proximal chromosome 3 (lod 6.1), and suggestive linkage with a locus on chromosome 14. A major locus on mid-chromosome 7 controlled width of the diaphysis (lod 6.8). Other loci were identified on chromosomes 2 and 4. Width at the intertrochanteric region had suggestive linkage with loci on chromosomes 6 and 19. No loci were found with linkage for width of the femoral head. Candidate genes related to bone development or metabolism are present at most of these loci. These findings show that genetic regulation of femoral bone morphology is complex, and are consistent with the distinct biologic processes that control longitudinal and lateral growth of the femur.
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The sequencing of the human genome has resulted in greater attention to genetic variation among individuals, and variation at the DNA sequence level is now being extensively studied. At the same time, it has become possible to study variation at the level of gene expression by various methods. At present, it is largely unknown how widespread this variation in transcript levels is over the entire genome and to what extent individual differences in expression level are genetically determined. In the present study, we used lymphoblastoid cells to examine variation in gene expression and identified genes whose transcript levels differed greatly among unrelated individuals. We also found evidence for familial aggregation of expression phenotype by comparing variation among unrelated individuals, among siblings within families and between monozygotic twins. These observations suggest that there is a genetic contribution to polymorphic variation in the level of gene expression.
Green Revolution rice varieties deliver high yields but require excessive nitrogen (N) fertilizer and show diminished N responsiveness, severely reducing nitrogen-use efficiency (NUE). To dissect the molecular basis of low N sensitivity in modern cultivars, we conducted a genome-wide association study (GWAS) for biomass response to N (BRN), a trait tightly linked to N sensitivity, using a diverse rice germplasm panel. We identified BRN1 as a key regulator of N-dependent biomass accumulation that regulates NLP3, a master transcription factor governing nitrate signaling. Under elevated N supply, the strigolactone signaling repressor D53 accumulates substantially and interacts with BRN1 to repress NLP3 transcription, thereby reducing rice N response. Notably, the high-response BRN1H allele encodes a more stable protein that alleviates D53-mediated suppression. Introgression of this allele into modern cultivars significantly enhanced N sensitivity and grain yield under both low and high N conditions. Our findings establish a D53-BRN1-NLP3 regulatory module controlling rice NUE, providing a target for rice breeding to sustain high productivity with improved resource sustainability.
Most organismal traits result from the complex interplay of many genetic and environmental factors, making their prediction difficult. Here, we used machine learning (ML) models to explore phenotype predictions for 223 traits measured across 1011 genome-sequenced Saccharomyces cerevisiae strains isolated worldwide. We benchmarked a ML pipeline with multiple linear and non-linear models to predict phenotypes from genotypes and gene expression, and determined gradient boosting machines as the best-performing model. Gene function disruption scores and gene presence/absence emerged as best predictors, suggesting a considerable contribution of the accessory genome in controlling phenotypes. The prediction accuracy broadly varied among phenotypes, with stress resistance being easier to predict compared to growth across nutrients. ML identified relevant genomic features linked to phenotypes, including high-impact variants with established relationships to phenotypes, despite these being rare in the population. Near-perfect accuracies were achieved when other phenomics data mostly in similar conditions were used, suggesting that useful information can be conveyed across phenotypes. Overall, our study underscores the power of ML to interpret the functional outcome of genetic variants.
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Adult hippocampal neurogenesis is highly variable and heritable among laboratory strains of mice. Adult neurogenesis is also remarkably plastic and can be modulated by environment and activity. Here, we provide a systematic quantitative analysis of adult hippocampal neurogenesis in two large genetic reference panels of recombinant inbred strains (BXD and AXB/BXA, n = 52 strains). We combined data on variation in neurogenesis with a new transcriptome database to extract a set of 190 genes with expression patterns that are also highly variable and that covary with rates of (i) cell proliferation, (ii) cell survival, or the numbers of surviving (iii) new neurons, and (iv) astrocytes. Expression of a subset of these neurogenesis-associated transcripts was controlled in cis across the BXD set. These self-modulating genes are particularly interesting candidates to control neurogenesis. Among these were musashi (Msi1h) and prominin1/CD133 (Prom1), both of which are linked to stem-cell maintenance and division. Twelve neurogenesis-associated transcripts had significant cis-acting quantitative trait loci, and, of these, six had plausible biological association with adult neurogenesis (Prom1, Ssbp2, Kcnq2, Ndufs2, Camk4, and Kcnj9). Only one cis-acting candidate was linked to both neurogenesis and gliogenesis, Rapgef6, a downstream target of ras signaling. The use of genetic reference panels coupled with phenotyping and global transcriptome profiling thus allowed insight into the complexity of the genetic control of adult neurogenesis.