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PubMed1998

The evolution of grass genome organisation and function.

New cloning technologies and more efficient DNA sequencing now permit comprehensive structural studies of complex eukaryotic genomes. Previous global investigations of genome organisation in plants had shown that abundant repetitive DNAs were intermixed with genes. However, the nature of the major repeats, their possible biological roles, their origins, and their precise patterns of organisation were not clearly defined. My laboratory has used large clones derived from homologous regions of the maize, sorghum and rice genomes to investigate the nature, functional properties and evolution of grass genome organisation. Unexpectedly simple patterns of genome composition and arrangement have been seen, and these appear to be similar in different grasses. Our detailed studies of the maize genome indicate that short (2-20 kb) blocks of gene-containing DNA alternate with large (2-200 kb) blocks of intermixed middle and highly repetitive DNAs. Most of the highly repetitive sequences, and many of the middle repetitive DNAs, are retrotransposons that have inserted within each other. These repetitive DNAs are usually methylated and mostly inactive, but they are homologous to transcripts found in many different tissues. The unmethylated DNA is composed primarily of genes interspersed with lower-copy-number retroelements and inverted-repeat transposable elements. Gene order and sequence are highly conserved, but the mobile DNAs between genes appear to be different due to their rapid evolution and their variable presence or locations in different grasses.

Chromosome Mapping↗

PubMed2001

Centrosome defects can account for cellular and genetic changes that characterize prostate cancer progression.

Factors that determine the biological and clinical behavior of prostate cancer are largely unknown. Prostate tumor progression is characterized by changes in cellular architecture, glandular organization, and genomic composition. These features are reflected in the Gleason grade of the tumor and in the development of aneuploidy. Cellular architecture and genomic stability are controlled in part by centrosomes, organelles that organize microtubule arrays including mitotic spindles. Here we demonstrate that centrosomes are structurally and numerically abnormal in the majority of prostate carcinomas. Centrosome abnormalities increase with increasing Gleason grade and with increasing levels of genomic instability. Selective induction of centrosome abnormalities by elevating levels of the centrosome protein pericentrin in prostate epithelial cell lines reproduces many of the phenotypic characteristics of high-grade prostate carcinoma. Cells that transiently or permanently express pericentrin exhibit severe centrosome and spindle defects, cellular disorganization, genomic instability, and enhanced growth in soft agar. On the basis of these observations, we propose a model in which centrosome dysfunction contributes to the progressive loss of cellular and glandular architecture and increasing genomic instability that accompany prostate cancer progression, dissemination, and lethality.

Antigens↗

PubMed2004

Oncogene expression and genetic background influence the frequency of DNA copy number abnormalities in mouse pancreatic islet cell carcinomas.

Quantitative measurements of tumor genome composition show remarkable heterogeneity in tumors arising from the same anatomical location and/or histopathological class and stage. The factors that contribute to genomic heterogeneity are not clear, but germ-line allelic variation and timing of initiating oncogenic events are likely candidates. We investigated these factors by using array comparative genomic hybridization to measure genomic aberrations in genetically engineered mouse models of pancreatic islet cell carcinoma, in which oncogenic transformation is elicited by the SV40 T antigens expressed under the control of the rat insulin promoter (RIP-Tag). Two distinct transgenic RIP-Tag lines, and three polymorphic sublines of one, enabled us to investigate the effects of genetic background and differing age of oncogene induction. Both parameters were found to bias the spectrum of genomic copy number abnormalities. Specifically, the frequency of losing portions of chromosomes 9 and 16 was significantly modulated by genetic background, with the former being lost at highest rates in the FVB/N background and the latter being lost to greatest extent in both FVB/N and C57Bl/6 tumors compared with C3HeB/Fe tumors. The frequency of losing a region of chromosome 6 varied according to the age when tumorigenesis was initiated; loss of chromosome 6 was significantly higher when oncogene expression was first activated in adulthood. These studies illustrate the utility of transgenic animal models for investigation of factors influencing genomic heterogeneity despite the commonalty of target cell type and initiating oncogene.

Animals↗

PubMed2003

Pharmacogenomic considerations for immunosuppressive therapy.

Immunosuppression, the art of suppressing the endogenous immune system to allow organ transplantation or treatment of autoimmune disease, is a clinico-pharmacological field that has markedly developed over the past three decades with the advent of highly potent and rationally targeted immunosuppressive agents. Pharmacogenomics, the art of providing tailored pharmacological therapy with the highest therapeutic index based on the genomic composition of the individual, is a science that has rapidly developed over the past decade, along with the advances in the human genome project and in biotechnology. Pharmacogenomics of immunosuppression is the combined art of tailoring specific immunosuppressive drug therapy to specific immune-mediated clinical entities which require immunosuppression, with optimum matching of the drug to the individual's genomic makeup. Timely and judicious application of pharmacogenomics to clinical immunosuppression should direct the clinician to the best immunosuppressive drug for any given clinical condition, and markedly increase its efficacy as well as decreasing the incidence of side effects and toxicity, thereby decreasing morbidity and prolonging survival. Is this a description of an ongoing clinical evolution in immunosuppression or a prediction of future events? The promises of pharmacogenomics of immunosuppression are high, yet the availability and/or application and/or realization of the promises of this highly specialized clinical science are very slow to come.

Drug Design↗

PubMed2003

Microarray analyses of Xylella fastidiosa provide evidence of coordinated transcription control of laterally transferred elements.

Genetically distinct strains of the plant bacterium Xylella fastidiosa (Xf) are responsible for a variety of plant diseases, accounting for severe economic damage throughout the world. Using as a reference the genome of Xf 9a5c strain, associated with citrus variegated chlorosis (CVC), we developed a microarray-based comparison involving 12 Xf isolates, providing a thorough assessment of the variation in genomic composition across the group. Our results demonstrate that Xf displays one of the largest flexible gene pools characterized to date, with several horizontally acquired elements, such as prophages, plasmids, and genomic islands (GIs), which contribute up to 18% of the final genome. Transcriptome analysis of bacteria grown under different conditions shows that most of these elements are transcriptionally active, and their expression can be influenced in a coordinated manner by environmental stimuli. Finally, evaluation of the genetic composition of these laterally transferred elements identified differences that may help to explain the adaptability of Xf strains to infect such a wide range of plant species.

Chromosome Mapping↗

PubMed2005

Transposable elements--is there a link between evolution and cancer?

Currently, the most predominant theory concerning the formation of cancer is that it is a genetic accident. Accordingly, various agents are thought to cause DNA damage which then subsequently activates oncogenes and inactivates tumor suppressor genes. This article, however, describes a theory that interprets cancer as a misguided adaptation. Stressors, which cannot be compensated for with the usual cell possibilities might arouse evolutionary mechanisms intended to create new protein variants. One of these is the activation of transposable elements which leads to a reformatting of the genome. The result of this process is either a cell that survives very well under stress (and will, therefore, never be detected), a dead cell (in case the process is ineffective), or a more or less abnormal and harmful cell that builds up a new but cancerous organ. This theory explains the complex genetic alterations which are present in almost all cancer cells. It also explains the action of non-mutagenic carcinogens. As part of the reformatting process of the cancer cell genome, activation of oncogenes and inactivation of tumor suppressor genes are not stochastic events but the result of an unlucky genomic composition.

Carcinogens↗

PubMed2023

Comparative transmission genetics of introgressed chromatin in reciprocal advanced backcross populations in Gossypium (cotton) polyploids.

Introgression is a potential source of valuable genetic variation and interspecific introgression lines are important resources for plant breeders to access novel alleles. Experimental advanced-generation backcross populations contain individuals with genomic compositions similar to those resulting from natural interspecific hybridization and provide opportunities to study the nature and transmission pattern of donor chromatin in recipient genomes. Here, we analyze transmission of donor chromatin in reciprocal backcrosses between G. hirsutum and G. barbadense. Across the genome, recurrent backcrossing in both backgrounds yielded donor chromatin at slightly higher frequencies than the Mendelian expectation in BC5F1 plants, while the average frequency of donor alleles in BC5F2 segregating families was less than expected. In the two subgenomes of polyploid cotton, the rate of donor chromatin introgression was similar. Although donor chromatin was tolerated over much of the recipient genomes, 21 regions recalcitrant to donor alleles were identified. Only limited correspondence is observed between the recalcitrant regions in the two backgrounds, suggesting the effect of species background on introgression of donor segments. Genetic breakdown was progressive, with floral abscission and seed inviability ongoing during backcrossing cycles. Regions of either high or low introgression tended to be in terminal chromosomal regions that are generally rich in both genes and crossover events, with long stretches around the centromere having limited crossover activity resulting in relatively constant low introgression frequencies. Constraints on fixation and selection of donor alleles highlights the challenges of utilizing introgression breeding in crop improvement.

Humans↗

PubMed2000

Evolutionary change of codon usage for the histone gene family in Drosophila melanogaster and Drosophila hydei.

The nucleotide divergence in the protein-coding region for replication-dependent and replication-independent histone 3 and 4 genes of Drosophila melanogaster and Drosophila hydei occurred mostly at the synonymous site. Therefore, the pattern of codon usage was analyzed in the two species, considering the genomic codon bias, which is proposed for estimating the genomic composition pressure in the protein-coding regions. The results indicated that the codon usage in the histone gene family could be explained mostly by the genomic codon bias. However, biases for Ala and Arg were commonly observed for the histone 3 and histone 4 gene families, and biases for Ser, Leu, and Glu were observed in a gene-specific manner. This suggests that both genomic codon bias and gene- or codon-specific bias are responsible for the nucleotide differentiation in the protein-coding region of the histone genes.

Animals↗

PubMed2006

Directionality of point mutation and 5-methylcytosine deamination rates in the chimpanzee genome.

BACKGROUND: The pattern of point mutation is important for studying mutational mechanisms, genome evolution, and diseases. Previous studies of mutation direction were largely based on substitution data from a limited number of loci. To date, there is no genome-wide analysis of mutation direction or methylation-dependent transition rates in the chimpanzee or its categorized genomic regions. RESULTS: In this study, we performed a detailed examination of mutation direction in the chimpanzee genome and its categorized genomic regions using 588,918 SNPs whose ancestral alleles could be inferred by mapping them to human genome sequences. The C-->T (G-->A) changes occurred most frequently in the chimpanzee genome. Each type of transition occurred approximately four times more frequently than each type of transversion. Notably, the frequency of C-->T (G-->A) was the highest in exons among the genomic categories regardless of whether we calculated directly, normalized with the nucleotide content, or removed the SNPs involved in the CpG effect. Moreover, the directionality of the point mutation in exons and CpG islands were opposite relative to their corresponding intergenic regions, indicating that different forces govern the nucleotide changes. Our analysis suggests that the GC content is not in equilibrium in the chimpanzee genome. Further quantitative analysis revealed that the 5-methylcytosine deamination rates at CpG sites were highly dependent on the local GC content and the lengths of SNP flanking sequences and varied among categorized genomic regions. CONCLUSION: We present the first mutational spectrum, estimated by three different approaches, in the chimpanzee genome. Our results provide detailed information on recent nucleotide changes and methylation-dependent transition rates in the chimpanzee genome after its split from the human. These results have important implications for understanding genome composition evolution, mechanisms of point mutation, and other genetic factors such as selection, biased codon usage, biased gene conversion, and recombination.

5-Methylcytosine↗

PubMed2004

Genomic relationships among diploid and hexaploid species of Andropogon (Poaceae).

Andropogon is a pantropical grass genus comprising 100-120 species and found mainly in the grasslands of Africa and the Americas. While the genomic relationships between many Andropogon species have been resolved by studying chromosome behavior in interspecific hybrids, relationships between the North and South American diploids have remained elusive. Further, the genome composition of two hexaploid species (including the important forage grass Andropogon lateralis Nees) has been unclear because of the strong hybridization barriers that exist between species. Consequently, genomic in situ hybridization was applied to shed light on these issues. The results confirmed that (i) both the South American (Andropogon selloanus (Hack.) Hack., Andropogon macrothrix Trin.) and North American (Andropogon gyrans Michx.) diploid species shared a common S genome and (ii) the S genome comprises just one of the three genomes in the hexaploids A. lateralis Nees and Andropogon bicornis L. The evolutionary and taxonomic implications of these findings are discussed.

Chromosomes↗

PubMed2005

Rate of chromosome changes and speciation in reptiles.

The chromosome changing rate (i.e. the number of chromosome rearrangements per million years) was studied in 1,329 reptile species in order to evaluate the karyological evolutionary trend and the existence of possible correlations between chromosome mutations and some aspects of the evolution of this class. The results obtained highlight the existence of a general direct correlation between chromosome changing rate and number of living species, although different trends can be observed in the different orders and suborders. In turtles, the separation of pleurodires from cryptodires was accompanied by a considerable karyological diversification. Among pleurodires, the evolution of the Chelidae and Pelomedusidae was also characterised by chromosome variation, while in cryptodires a marked karyological homogeneity is observed between and within infra-orders. Similarly there is no correlation between changing rate and species number in crocodiles, where the evolution of the families and genera has entailed few chromosome mutations. Chromosome variability was greater in lizards and snakes. In the formers variations in chromosome changing rate accompanied the separation of the infra-orders and the evolution of most of the families and of some genera. The origin of snakes has also been accompanied by a marked karyological diversification, while the subsequent evolution of the infra-orders and families has entailed a high level of chromosome variability only in colubroids. The karyological evolution in reptiles generally entailed a progressive reduction in chromosome changing rate, albeit with differences in the diverse orders and suborders. This trend seems to be consistent with the "canalization model" as originally proposed by Bickham and Baker in [Bickham, J.W. & R J. Baker, 1979. Bull. Carnegie Mus. Nat. Hist. 13: 70-84.] However, several inconsistencies have been found excluding that in this class the ultimate goal of chromosome variations was the achievement of a so-called "optimum karyotype'' as suggested by the above-mentioned theory. Other mechanisms could underpin chromosome variability in Reptiles. Among them a genomic composition more or less favourable to promoting chromosome rearrangements and factors favouring the fixation of a mutant karyotype in condition of homozygosis. Turtles and crocodiles would have a genome characterised by large chromosomes and a low level of chromosome compartmentalisation limiting the recombination and the frequency of rearrangements. A low rate of chromosome variability modifying little if at all the gene linkage groups would have favoured a conservative evolutionary strategy. In the course of evolution, lizards and snakes could have achieved a genome characterised by smaller chromosomes and a higher level of compartmentalisation. This would have raised the frequency of recombination and consequently an evolutionary strategy promoting a higher degree of variability and a greater level of speciation.

Animals↗

PubMedDate not supplied

[The level of DNA homology in species of the genus Cytophaga].

Nucleotide composition, genome size and DNA homologies were studied for strains Cytophaga johnsonae DSM 425, C. pectinovora DSM 6368, C. saccharophyla DSM 1811, C. aquatilis DSM 2063, C. flevensis DSM 1076, C. lytica ATCC 23 178, C. arvensicola DSM 3695, C. heparina DSM 2356. A considerable difference in GS-bases level between species of genus Cytophaga (33.3-34.9 mol %) and incertae sedis species (C. heparina and C. arvensicola) (45.0-46.7 mol. %) was shown. The differentiation between freshwater and soil, on the one hand, and seawater species, on the other hand, was determined. The degree of DNA-resemblance between them was 2-13%. The existence of relationship between freshwater and soil species was demonstrated. The homology in DNA of freshwater and soil species (C. johnsonae, C. pectinovora and C. saccharophyla) was 22-37%. The heterogeneity of genus Cytophaga and the necessity of its revision are supported.

Base Composition↗

PubMed1996

Computational comparisons of model genomes.

Complete genomes from model organisms provide new challenges for computational molecular biology. Novel questions emerge from the genome data obtained from the functional prediction of thousands of gene products. In this review, we present some approaches to the computational comparison of genomes, based on sequence and text analysis, and comparisons of genome composition and gene order.

Biotechnology↗

PubMedDate not supplied

Characteristics of Chi distribution on different bacterial genomes.

The availability of full genome sequences provides the bases for analyzing global properties of the genetic text. For example, oligonucleotide sequences that are over- or underrepresented can be identified by taking into account the overall genome composition and organization. One of the most overrepresented oligonucleotides in Escherichia coli is the Chi site, an octanucleotide that stimulates DNA repair by homologous recombination. Here we analyze the genomic distribution of Chi in E. coli and in the three other bacteria where a Chi sequence has been identified; note that Chi is a different sequence in each organism. For each bacterial genome, Chi sequences are frequent, regularly distributed, and overrepresented. This suggests that selection for Chi may have occurred during evolution to favor efficient repair of a damaged chromosome. Other characteristics of Chi distribution are not conserved and might reflect specific features of DNA repair in each host. The different sequence and characteristics of Chi in each microorganism suggest that selection for Chi occurred independently in different bacteria.

Bacillus subtilis↗

PubMed2002

Painting of parental chromatin in Beta hybrids by multi-colour fluorescent in situ hybridization.

Sugar beet (Beta vulgaris L.) is a relatively young crop and has a narrow gene pool. In order to introduce genetic variability into the crop, interspecific hybrids, selected from crosses with wild beets of the sections Corollinae and Procumbentes, have been generated. The introgressed B. procumbens chromatin carries resistance genes to beet cyst nematode Heterodera schachtii Schm. These lines are important for breeding of nematode-resistant sugar beet, while Corollinae species are potential donors of tolerance to biotic and abiotic stresses such as drought or saline soils. We have used in situ hybridization of genomic DNA to discriminate the parental chromosomes in these interspecific hybrids. Suppression of cross-hybridization by blocking DNA was not necessary indicating that the investigated Beta genomes contain sufficient species-specific DNA enabling the unequivocal determination of the genomic composition of the hybrids. Interspecific hybrid lines with an additional chromosome (2n = 18 + 1), chromosome fragment (2n = 18 + fragment) or translocation of B. procumbens (2n = 18) were analysed by genomic in situ hybridization (GISH) at mitosis and meiosis. Species-specific satellites and ribosomal genes used in combination with genomic DNA or in rehybridization experiments served as landmark probes for chromosome identification in hybrid genomes. The detection of a B. procumbens translocation of approx. I Mbp demonstrated the sensitivity and resolution of GISH and showed that this approach is a powerful method in genome analysis projects of the genus Beta.

Animals↗

PubMed1995

Drosophila melanogaster mitochondrial DNA: completion of the nucleotide sequence and evolutionary comparisons.

The nucleotide sequence of the regions flanking the A+T region of Drosophila melanogaster mitochondrial DNA (mtDNA) has been determined. Included are the genes encoding the transfer RNAs for valine, isoleucine, glutamine and methionine, the small ribosomal RNA and the 5'-coding sequences of the large ribosomal RNA and NADH dehydrogenase subunit II. This completes the nucleotide sequence of the D. melanogaster mitochondrial genome. The circular mtDNA of D. melanogaster varies in size among different populations largely due to length differences in the control region (Fauron & Wolstenholme, 1976; Fauron & Wolstenholme, 1980a, b); the mtDNA region we have sequenced, combined with those sequenced by others, yields a composite genome that is 19,517 bp in length as compared to 16,019 bp for the mtDNA of D. yakuba. D. melanogaster mtDNA exhibits an extreme bias in base composition; it comprises 82.2% deoxyadenylate and thymidylate residues as compared to 78.6% in D. yakuba mtDNA. All genes encoded in the mtDNA of both species are in identical locations and orientations. Nucleotide substitution analysis reveals that tRNA and rRNA genes evolve at less than half the rate of protein coding genes.

Amino Acid Sequence↗

PubMed1993

A cytometric exercise in plant DNA histograms, with 2C values for 70 species.

An introduction is given to the literature concerning methods and objectives for cytometric DNA analysis of plant nuclei. This area has gained relevance with applications in plant breeding and seed production industries, where laboratories unfamiliar with cytometry are adopting the method. An extensive graphical guide to interpreting DNA histograms and their problems is given. Conversely, cytometry laboratories unfamiliar with plant sciences will find herein a guide, and references, to adapt their methods to plant material. A table of 2C values reassessed by flow cytometry for 70 plant species, plus the genome composition (GC%) in many instances, is also included.

Cell Cycle↗

PubMed1992

Ancestry of unisexual salamanders.

In eastern North America there are populations of all-female salamanders that incorporate the nuclear genomes of two or three of four sympatric bisexual species. The hybrids can be diploid, triploid, tetraploid or pentaploid, and 18 different combinations have been reported. All hybrids require sperm from a sympatric male of one of the bisexual species to reproduce, but the sperm may or may not be incorporated in the egg. Some of the hybrids are believed to represent separate, clonal species, but little is known of the origin of this hybrid complex. Vertebrate mitochondrial DNA is inherited maternally, allowing identification of the female parent that gave rise to hybrid lineages. A portion of the cytochrome b gene was sequenced from diploid and triploid hybrids that represent combinations of all four species. Nearly all hybrids had a similar mitochondrial genome sequence, independent of nuclear genome composition and ploidy, and the sequence was distinct from that of any of the four bisexual species. The hybrids maintain a mitochondrial lineage that has evolved independently of their nuclear genome and represent the most ancient known unisexual vertebrate lineage.

Ambystoma↗