Biomedical subjects

Genomics

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PubMed2004

Genomic biomarkers for cancer assessment: implementation challenges for laboratory practice.

Genomic biomarkers are an emerging class of laboratory tests, which present special implementation challenges for clinical laboratory services, compared to conventional laboratory tests. These challenges, which include analytical, bioinformatics, bioethical, interpretation and commercialization issues, represent real obstacles to widespread implementation of these tests. Technical challenges include the capacity to detect and identify many different kinds of markers for different diseases in a short time period, capacity to identify simultaneously gene rearrangements, amplification, inhibition, deletions and replications. Bioinformatics challenges include rapid analysis of genomic data, as well as the cross reference to other genomic data, and to other laboratory tests. Bioethical issues relate to consent to retain and use genetic data, which may be obtained inadvertently during analysis for genomic markers. Interpretation challenges include observations that the particular genomic markers may not be independent variables, as other undetected genomic alterations could invalidate or alter genomic marker interpretation. Further, as early experience with predictive genetic markers for cancer has shown, proprietary commercial interests may conflict with public health values of identifying genomic markers in subject populations. Based on our 10 years of experience with genomic biomarkers, important implementation strategies for genomic markers include development of:Standard high throughput analyzers capable of detecting any alteration of any genomic variant at any time. Bioinformatics analysis online, coupled to stored patient data. Laboratory service framework that preserves confidentiality but integrates genomic data with other laboratory tests. Laboratory service framework, which links consents, genomic analysis, reports to both specimen and data repositories. Overall, the laboratory service challenges for genomic markers are to manage very large analytical sets and very large data sets in finite time with responsible interpretation, all within finite funding. To meet these challenges, implementation strategies beyond the one disease, one diagnosis, one genomic marker concept must begin now.

Biomarkers, Tumor↗

PubMed2004

Guanosine distribution and oxidation resistance in eight eukaryotic genomes.

Reactive oxygen species that attack DNA are continuously generated in living cells. Both the guanosine (G) mole fraction and its distribution should affect the stability of genomes and their parts to oxidation. At a lesser G content, genomes should be more oxidation resistant or "ennobled". Oxidant scavenging by G's in nonessential parts of introns and intergenic domains should decrease G oxidation in the essential exons. To determine whether genomes are indeed ennobled and whether oxidant-scavenging domains exist in genomes, the relative rates of guanosine oxidation in average exons, introns, and intergenic domains were estimated. Comparison among genomes indicated that average exons are ennobled in the genomes of Caenorhabditis (worm), Arabidopsis (plant), Saccharomyces (yeast), Schizosaccharomyces (yeast), and Plasmodium (malaria parasite), and that average introns and intergenic domains are ennobled in these genomes and in the genome of Drosophila (fly). The exon oxidation rates estimated for these genomes were less than the rate for the hypothetical "standard" genome, with a 0.25 mole fraction of uniformly distributed G. For Plasmodium the rate was half of that estimated for the standard genome. Average exons were not ennobled in the human or fly genomes; their G distributions were comparable to that in the standard genome. Instead, their exons were situated between introns and intergenic domains that could protect them by oxidant scavenging, the G's of their introns and intergenic domains outnumbering those of their exons 50-fold in humans and 4-fold in flies. The G distribution in the Encephalitozoon (parasite) genome was not protective relative to that of the standard genome.

Animals↗

PubMed2000

Inherent instability of poliovirus genomes containing two internal ribosome entry site (IRES) elements supports a role for the IRES in encapsidation.

Previous studies have described poliovirus genomes in which the internal ribosome entry (IRES) for encephalomyocarditis virus (EMCV) is positioned between the P1 and P2-P3 open reading frames of the poliovirus genome. Although these dicistronic poliovirus genomes were replication competent, most exhibited evidence of genetic instability, and the EMCV IRES was deleted upon serial passage. One possible reason for instability of the genome is that the dicistronic genome was at least 108% larger than the wild-type poliovirus genome, which could reduce the efficiency of encapsidation. To address this possibility, we have constructed dicistronic poliovirus replicons by substituting the EMCV IRES and the gene encoding luciferase in place of the poliovirus P1 region; the resulting dicistronic replicons are smaller than the wild-type poliovirus genome. One dicistronic genome was constructed in which the poliovirus 5' nontranslated region was fused to the gene encoding luciferase, followed by the complete EMCV IRES fused to the P2-P3 region of the poliovirus genome (PV-Luc-EMCV). A second dicistronic genome, EMCV-Luc-PV, was constructed with the first 108 nucleotides of the poliovirus genome fused to the EMCV IRES, followed by the gene encoding luciferase and the poliovirus IRES fused to the remaining P2-P3 region of the poliovirus genome. Both dicistronic replicons expressed abundant luciferase following transfection of in vitro-transcribed RNA into HeLa cells at 30, 33, or 37 degrees C. The luciferase activity detected from PV-Luc-EMCV increased rapidly during the first 4 h following transfection and then plateaued, peaking after approximately 24 h. In contrast, the luciferase activity detected from EMCV-Luc-PV increased for approximately 12 h following transfection; by 24 h posttransfection, the overall levels of luciferase activity were similar to that of PV-Luc-EMCV. To analyze encapsidation of the dicistronic replicons, we used a system in which the capsid protein (P1) is provided in trans from a recombinant vaccinia virus (VV-P1). The PV-Luc-EMCV replicon was unstable upon serial passage in the presence of VV-P1, with deletions of the EMCV IRES region detected even during the initial transfection at 37 degrees C. Following serial passage in the presence of VV-P1 at 33 or 30 degrees C, we detected deleted genomes in which the luciferase gene was fused with the P2-P3 genes of the poliovirus genome so as to maintain the translational reading frame. In contrast, the EMCV-Luc-PV replicon was genetically stable during passage with VV-P1 at 33 or 30 degrees C. The encapsidation of EMCV-Luc-PV was compared to that of monocistronic replicons encoding luciferase with either a poliovirus or EMCV IRES. Analysis of the encapsidated replicons after four serial passages with VV-P1 revealed that the dicistronic replicon was encapsidated more efficiently than the monocistronic replicon with the EMCV IRES but less efficiently than the monicistronic replicon with the poliovirus IRES. The results of this study suggest a genetic predisposition for picornavirus genomes to contain a single IRES region and are discussed with respect to a role of the IRES in encapsidation.

5' Untranslated Regions↗

PubMed1995

Molecular analysis of evolutionary patterns in U genome wild wheats.

The theory of pivotal-differential evolution states that one genome of polyploid wheats remains stable (i.e., pivotal) during evolution, while the other genome or genomes may become modified (i.e., differential). A proposed mechanism for apparent modification of the differential genome is that different polyploid species with only one genome in common may exchange genetic material. In this study, we analyzed a set of sympatric and allopatric accessions of tetraploid wheats with the genomic constitutions UM and UC. The U genome of these species is from Triticum umbellulatum and is considered to be the pivotal genome. The M and C genomes, from T. comosum and T. dichasians, respectively, are considered to be the differential genomes. Low copy DNA was analyzed using "sequence tagged site" primer sets in the polymerase chain reaction, followed by digestion with restriction enzymes. Genetic similarity matrices based on shared restriction fragments showed that sympatric accessions of different U genome tetraploid species did not tend to share more restriction fragments than did allopatric accessions. Thus, no evidence for introgression was found. Analysis of the diploid progenitor species showed that the U genome was less variable than the M and C genomes. Additionally, comparison of diploid and polyploid species using genome-specific primer sets suggests a possible polyphyletic origin for T. triunciale and T. machrochaetum. Thus, our results suggest that the differential nature of the M and C genomes may be the result of variability introduced by the diploid progenitors and not the result of frequent introgression events after formation of the polyploid.

Base Sequence↗

PubMed2005

What transposable elements tell us about genome organization and evolution: the case of Drosophila.

Transposable elements (TEs) have been identified in every organism in which they have been looked for. The sequencing of large genomes, such as the human genome and those of Drosophila, Arabidopsis, Caenorhabditis, has also shown that they are a major constituent of these genomes, accounting for 15% of the genome of Drosophila, 45% of the human genome, and more than 70% in some plants and amphibians. Compared with the 1% of genomic DNA dedicated to protein-coding sequences in the human genome, this has prompted various researchers to suggest that the TEs and the other repetitive sequences that constitute the so-called "noncoding DNA", are where the most stimulating discoveries will be made in the future (Bromham, 2002). We are therefore getting further and further from the original idea that this DNA was simply "junk DNA", that owed its presence in the genome entirely to its capacity for selfish transposition. Our understanding of the structures of TEs, their distribution along the genomes, their sequence and insertion polymorphisms within genomes, and within and between populations and species, their impact on genes and on the regulatory mechanisms of genetic expression, their effects on exon shuffling and other phenomena that reshape the genome, and their impact on genome size has increased dramatically in recent years. This leads to a more general picture of the impact of TEs on genomes, though many copies are still mainly selfish or junk DNA. In this review we focus mainly on discoveries made in Drosophila, but we also use information about other genomes when this helps to elucidate the general processes involved in the organization, plasticity, and evolution of genomes.

Animals↗

PubMed2006

Rapid and accurate pyrosequencing of angiosperm plastid genomes.

BACKGROUND: Plastid genome sequence information is vital to several disciplines in plant biology, including phylogenetics and molecular biology. The past five years have witnessed a dramatic increase in the number of completely sequenced plastid genomes, fuelled largely by advances in conventional Sanger sequencing technology. Here we report a further significant reduction in time and cost for plastid genome sequencing through the successful use of a newly available pyrosequencing platform, the Genome Sequencer 20 (GS 20) System (454 Life Sciences Corporation), to rapidly and accurately sequence the whole plastid genomes of the basal eudicot angiosperms Nandina domestica (Berberidaceae) and Platanus occidentalis (Platanaceae). RESULTS: More than 99.75% of each plastid genome was simultaneously obtained during two GS 20 sequence runs, to an average depth of coverage of 24.6x in Nandina and 17.3x in Platanus. The Nandina and Platanus plastid genomes shared essentially identical gene complements and possessed the typical angiosperm plastid structure and gene arrangement. To assess the accuracy of the GS 20 sequence, over 45 kilobases of sequence were generated for each genome using conventional sequencing. Overall error rates of 0.043% and 0.031% were observed in GS 20 sequence for Nandina and Platanus, respectively. More than 97% of all observed errors were associated with homopolymer runs, with approximately 60% of all errors associated with homopolymer runs of 5 or more nucleotides and approximately 50% of all errors associated with regions of extensive homopolymer runs. No substitution errors were present in either genome. Error rates were generally higher in the single-copy and noncoding regions of both plastid genomes relative to the inverted repeat and coding regions. CONCLUSION: Highly accurate and essentially complete sequence information was obtained for the Nandina and Platanus plastid genomes using the GS 20 System. More importantly, the high accuracy observed in the GS 20 plastid genome sequence was generated for a significant reduction in time and cost over traditional shotgun-based genome sequencing techniques, although with approximately half the coverage of previously reported GS 20 de novo genome sequence. The GS 20 should be broadly applicable to angiosperm plastid genome sequencing, and therefore promises to expand the scale of plant genetic and phylogenetic research dramatically.

Base Sequence↗

PubMed2004

Enrichment of transcriptional regulatory sites in non-coding genomic region.

MOTIVATION: Over-represented k-mers in non-coding genomic regions often lead to identification of potential transcriptional regulatory sites (TRS). This phenomenon has been employed by many algorithms to predict TRS in silico. Yet, the improvement of these algorithms should be based on deeper understanding of the enrichment feature. To obtain a general distributional profile of TRS in different regions of genomes as well as in different genomes, we here performed a systematic analysis on the over-representation of TRS in intergenic regions and gene upstream regions of yeasts and viral genomes, and the distributional pattern of TRS in intergenic and intron regions of the Drosophila genome. We also explored the way to evaluate the accuracy of TRS consensus sequences by measuring their enrichment. RESULTS: To measure enrichment, a statistical background model was introduced by comparing TRS frequency in certain regions of genome to either the frequency in the whole genome or the frequency in exon region. This model was applied to different classes of non-coding genomic regions in four genomes. Most of the TRS were observed to be over-represented in the intergenic regions of the Saccharomyces cerevisiae, Schizosaccharomyces pombe and Epstein-Barr virus (EBV) genomes. The enrichment of S.cerevisiae TRS in the 600 bp upstream region of genes was also significant. In Drosophila genome, TRS did not show enrichment in intergenic and intron regions when TRS frequency in the whole genome was taken as background, as we did in other genomes. However, when we took TRS frequency in exon region as background, over 70% TRS are over-represented in those two classes of non-coding regions. This fact indicates the existence of transcriptional regulatory signals in introns. The analysis of some S.cerevisiae TRS, which have inconsistent consensus sequences with different levels of enrichment in intergenic region, suggests the possibility of evaluating the accuracy of experimentally determined TRS by measuring their enrichment in non-coding genomic regions.

Algorithms↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

PubMed1987

Evolution of pseudorabies virions containing genomes with an invertible long component after repeated passage in chicken embryo fibroblasts.

The genome of pseudorabies virus consists of two components, short (S) and long (L). Only the S component is bracketed by inverted repeats, and only the S component inverts itself relative to the L component, giving rise to two isomeric forms of the genome. An attenuated vaccine strain of pseudorabies virus (Norden), however, has a genome which is found in four isomeric forms (B. Lomniczi, M. L. Blankenship, and T. Ben-Porat, J. Virol. 49:970-979, 1984). To determine the basis for the atypical structure of the genome of the Norden strain, we examined more than 40 field isolates of pseudorabies virus; all contained genomes in which the L component was fixed in only one orientation relative to the S component. Several independently generated vaccine strains which have been passaged extensively in chicken embryos and chicken embryo fibroblast (CEF) cell cultures were also analyzed; they possessed an invertible L component. Furthermore, emergence of pseudorabies virus variants with an invertible L component was observed after passage of the virus in CEF, but not in rabbit kidney or pig kidney, cells. The invertibility of the L component was associated consistently with a translocation of sequences from the left end of the genome to a position next to the inverted repeat sequence of the S component. Three observations indicate that genomes with an invertible L component (and the translocation) have a selective growth advantage over standard pseudorabies virus when grown in CEF. The proportion of virions with such genomes does not increase linearly as would be expected if the translocation events occurred repeatedly, most genomes eventually experiencing the translocation. Instead, after a lag, the proportion of such virions in the population increases relatively rapidly. The genome structures that are generated upon independent passage in CEF of each virion population were relatively homogeneous. Some heterogeneity was observed at relatively early stages of the emergence of the genomes carrying the translocation; at later stages, virions with genomes with a specific size translocation predominated in the virus population. Parallel passages in CEF of the same pseudorabies virus strain resulted in the emergence of populations of virions with genomes with different size translocations. However, in each of the passaged populations of virions the majority of virions had genomes with the same size translocation. The most likely interpretation of these results is that virions with genomes carrying the translocations that emerge upon passage of the virus in CEF have a selective advantage when grown in these cells.

Animals↗

PubMed2006

GenomeBlast: a web tool for small genome comparison.

BACKGROUND: Comparative genomics has become an essential approach for identifying homologous gene candidates and their functions, and for studying genome evolution. There are many tools available for genome comparisons. Unfortunately, most of them are not applicable for the identification of unique genes and the inference of phylogenetic relationships in a given set of genomes. RESULTS: GenomeBlast is a Web tool developed for comparative analysis of multiple small genomes. A new parameter called "coverage" was introduced and used along with sequence identity to evaluate global similarity between genes. With GenomeBlast, the following results can be obtained: (1) unique genes in each genome; (2) homologous gene candidates among compared genomes; (3) 2D plots of homologous gene candidates along the all pairwise genome comparisons; and (4) a table of gene presence/absence information and a genome phylogeny. We demonstrated the functions in GenomeBlast with an example of multiple herpesviral genome analysis and illustrated how GenomeBlast is useful for small genome comparison. CONCLUSION: We developed a Web tool for comparative analysis of small genomes, which allows the user not only to identify unique genes and homologous gene candidates among multiple genomes, but also to view their graphical distributions on genomes, and to reconstruct genome phylogeny. GenomeBlast runs on a Linux server with 4 CPUs and 4 GB memory. The online version of GenomeBlast is available to public by using a Web browser with the URL http://bioinfo-srv1.awh.unomaha.edu/genomeblast/.

Algorithms↗

PubMed2003

Quantifying the species-specificity in genomic signatures, synonymous codon choice, amino acid usage and G+C content.

Each prokaryote has a unique genomic signature as evidenced by a set of species-specific frequencies of short oligonucleotides. With respect to genomic signatures a bacterial genome is homogenous and the variation within a genome is smaller than the variations between genomes of different species. This study quantifies the species-specificity of genomic signatures in the complete genomes of 57 prokaryotes. The species-specificity in the genomic signature was related to the quantification of other sequence biases, such as G+C content, synonymous codon choice and amino acid usage. The results confirm that the genomic signature is genome-wide with high species-specificity in both coding and non-coding regions. In coding regions the species-specific bias in synonymous codon choice was comparable to the genomic signature, while the bias in amino acid usage only captured about 50% of the species-specific bias in the genomic signature. A correlation between the species-specificity in synonymous codon choice and amino acid usage was identified, in which proteins with species-specific amino acid usage were also coded with species-specific synonymous codon choice. However, we demonstrated that the G+C content captures only approximately 40% of the species-specificity in the genomic signature, and is insufficient to explain the species specificity in the non-coding regions. Thus, the species-specific bias in non-coding regions remains largely unknown. Further, we compared the genomic signature in relation to phylogenetic distance. This was performed in order to illustrate the feasibility of a hierarchical classification scheme in future applications of the described classification methodology in screening for horizontal gene transfer and biodiversity studies.

Amino Acids↗

PubMed2005

Gene identification in novel eukaryotic genomes by self-training algorithm.

Finding new protein-coding genes is one of the most important goals of eukaryotic genome sequencing projects. However, genomic organization of novel eukaryotic genomes is diverse and ab initio gene finding tools tuned up for previously studied species are rarely suitable for efficacious gene hunting in DNA sequences of a new genome. Gene identification methods based on cDNA and expressed sequence tag (EST) mapping to genomic DNA or those using alignments to closely related genomes rely either on existence of abundant cDNA and EST data and/or availability on reference genomes. Conventional statistical ab initio methods require large training sets of validated genes for estimating gene model parameters. In practice, neither one of these types of data may be available in sufficient amount until rather late stages of the novel genome sequencing. Nevertheless, we have shown that gene finding in eukaryotic genomes could be carried out in parallel with statistical models estimation directly from yet anonymous genomic DNA. The suggested method of parallelization of gene prediction with the model parameters estimation follows the path of the iterative Viterbi training. Rounds of genomic sequence labeling into coding and non-coding regions are followed by the rounds of model parameters estimation. Several dynamically changing restrictions on the possible range of model parameters are added to filter out fluctuations in the initial steps of the algorithm that could redirect the iteration process away from the biologically relevant point in parameter space. Tests on well-studied eukaryotic genomes have shown that the new method performs comparably or better than conventional methods where the supervised model training precedes the gene prediction step. Several novel genomes have been analyzed and biologically interesting findings are discussed. Thus, a self-training algorithm that had been assumed feasible only for prokaryotic genomes has now been developed for ab initio eukaryotic gene identification.

Algorithms↗

PubMed2005

A computational approach for identifying pathogenicity islands in prokaryotic genomes.

BACKGROUND: Pathogenicity islands (PAIs), distinct genomic segments of pathogens encoding virulence factors, represent a subgroup of genomic islands (GIs) that have been acquired by horizontal gene transfer event. Up to now, computational approaches for identifying PAIs have been focused on the detection of genomic regions which only differ from the rest of the genome in their base composition and codon usage. These approaches often lead to the identification of genomic islands, rather than PAIs. RESULTS: We present a computational method for detecting potential PAIs in complete prokaryotic genomes by combining sequence similarities and abnormalities in genomic composition. We first collected 207 GenBank accessions containing either part or all of the reported PAI loci. In sequenced genomes, strips of PAI-homologs were defined based on the proximity of the homologs of genes in the same PAI accession. An algorithm reminiscent of sequence-assembly procedure was then devised to merge overlapping or adjacent genomic strips into a large genomic region. Among the defined genomic regions, PAI-like regions were identified by the presence of homolog(s) of virulence genes. Also, GIs were postulated by calculating G+C content anomalies and codon usage bias. Of 148 prokaryotic genomes examined, 23 pathogenic and 6 non-pathogenic bacteria contained 77 candidate PAIs that partly or entirely overlap GIs. CONCLUSION: Supporting the validity of our method, included in the list of candidate PAIs were thirty four PAIs previously identified from genome sequencing papers. Furthermore, in some instances, our method was able to detect entire PAIs for those only partial sequences are available. Our method was proven to be an efficient method for demarcating the potential PAIs in our study. Also, the function(s) and origin(s) of a candidate PAI can be inferred by investigating the PAI queries comprising it. Identification and analysis of potential PAIs in prokaryotic genomes will broaden our knowledge on the structure and properties of PAIs and the evolution of bacterial pathogenesis.

Bacteria↗

PubMed2004

Low number of mitochondrial pseudogenes in the chicken (Gallus gallus) nuclear genome: implications for molecular inference of population history and phylogenetics.

BACKGROUND: Mitochondrial DNA has been detected in the nuclear genome of eukaryotes as pseudogenes, or Numts. Human and plant genomes harbor a large number of Numts, some of which have high similarity to mitochondrial fragments and thus may have been inadvertently included in population genetic and phylogenetic studies using mitochondrial DNA. Birds have smaller genomes relative to mammals, and the genome-wide frequency and distribution of Numts is still unknown. The release of a preliminary version of the chicken (Gallus gallus) genome by the Genome Sequencing Center at Washington University, St. Louis provided an opportunity to search this first avian genome for the frequency and characteristics of Numts relative to those in human and plants. RESULTS: We detected at least 13 Numts in the chicken nuclear genome. Identities between Numts and mitochondrial sequences varied from 58.6 to 88.8%. Fragments ranged from 131 to 1,733 nucleotides, collectively representing only 0.00078% of the nuclear genome. Because fewer Numts were detected in the chicken nuclear genome, they do not represent all regions of the mitochondrial genome and are not widespread in all chromosomes. Nuclear integrations in chicken seem to occur by a DNA intermediate and in regions of low gene density, especially in macrochromosomes. CONCLUSION: The number of Numts in chicken is low compared to those in human and plant genomes, and is within the range found for most sequenced eukaryotic genomes. For chicken, PCR amplifications of fragments of about 1.5 kilobases are highly likely to represent true mitochondrial amplification. Sequencing of these fragments should expose the presence of unusual features typical of pseudogenes, unless the nuclear integration is very recent and has not yet been mutated. Metabolic selection for compact genomes with reduced repetitive DNA and gene-poor regions where Numts occur may explain their low incidence in birds.

Animals↗

PubMed2003

Recent segmental and gene duplications in the mouse genome.

BACKGROUND: The high quality of the mouse genome draft sequence and its associated annotations are an invaluable biological resource. Identifying recent duplications in the mouse genome, especially in regions containing genes, may highlight important events in recent murine evolution. In addition, detecting recent sequence duplications can reveal potentially problematic regions of the genome assembly. We use BLAST-based computational heuristics to identify large (>/= 5 kb) and recent (>/= 90% sequence identity) segmental duplications in the mouse genome sequence. Here we present a database of recently duplicated regions of the mouse genome found in the mouse genome sequencing consortium (MGSC) February 2002 and February 2003 assemblies. RESULTS: We determined that 33.6 Mb of 2,695 Mb (1.2%) of sequence from the February 2003 mouse genome sequence assembly is involved in recent segmental duplications, which is less than that observed in the human genome (around 3.5-5%). From this dataset, 8.9 Mb (26%) of the duplication content consisted of 'unmapped' chromosome sequence. Moreover, we suspect that an additional 18.5 Mb of sequence is involved in duplication artifacts arising from sequence misassignment errors in this genome assembly. By searching for genes that are located within these regions, we identified 675 genes that mapped to duplicated regions of the mouse genome. Sixteen of these genes appear to have been duplicated independently in the human genome. From our dataset we further characterized a 42 kb recent segmental duplication of Mater, a maternal-effect gene essential for embryogenesis in mice. CONCLUSION: Our results provide an initial analysis of the recently duplicated sequence and gene content of the mouse genome. Many of these duplicated loci, as well as regions identified to be involved in potential sequence misassignment errors, will require further mapping and sequencing to achieve accuracy. A Genome Browser database was set up to display the identified duplication content presented in this work. This data will also be relevant to the growing number of investigators who use the draft genome sequence for experimental design and analysis.

Animals↗

PubMed2026

Complete telomere-to-telomere genome assembly of Guazuma ulmifolia uncovers evolutionary mechanisms, drought adaptation, and flavonoid biosynthesis.

The first T2T reference genome of Guazuma ulmifolia is reported, which serves as a core genomic resource for stress adaptation research and stress-tolerant breeding in cacao wild relatives. Climate change, particularly increased incidence of drought, poses a major threat to food security. Understanding the genomic basis of environmental adaptation in crop wild relatives can provide valuable resources for improving stress resilience. Guazuma ulmifolia, a wild relative of Theobroma cacao with important ecological and medicinal value, lacks high-quality reference genomic resources. Here, we report the first telomere-to-telomere (T2T) chromosome-level genome assembly of G. ulmifolia, with a genome size of 311.31 Mb, contig N50 of 35.19 Mb, and 98.70% BUSCO completeness. Repetitive sequences constitute 27.43% of the G. ulmifolia genome, with LTR retrotransposons as the predominant class. Comparative genomic analyses revealed that genome-size variation among Malvaceae species is associated with differences in polyploidization history and TE dynamics. Ancestral karyotype reconstruction identified five lineage-specific chromosome fusion events distinguishing G. ulmifolia from T. cacao. Comparative analyses further identified tandem duplication-associated expansion of stress-related LEA and GST gene families, suggesting potential genomic features associated with stress responses. Flavonoid biosynthesis genes were largely conserved in copy number but showed tissue-specific expression patterns, providing candidate genes for investigating secondary metabolism. Together, this study establishes a high-quality T2T genome resource for exploring genome evolution, chromosome organization, and stress-related genomic features in Malvaceae.

Genome, Plant↗

PubMed1999

Compositional correlation studies among the three different codon positions in 12 bacterial genomes.

Compositional distributions in the three codon positions of the coding sequences of 12 fully sequenced prokaryotic genomes, which are publicly available, were investigated. A universal compositional correlation was observed in most of the genomes under investigation irrespective of their overall genomic GC contents. In all the genomes, the GC contents at the first codon positions are always greater than the overall GC contents of the genomes whereas the reverse is true in the case of second codon positions. GC contents at the third codon positions are higher than the overall genomic GC contents in high GC containing genomes, and the opposite situation was found in case of low GC genomes except for Helicobacter pylori. In high-GC rich genomes, the GC contents at the first + second codon positions are less than the GC contents at the third codon positions, and they are low in low-GC genomes except for Helicobacter pylori. The distributions of four bases at the three different positions were also investigated for all 12 organisms. It was observed that in high-GC genomes G is the most dominant base and in low-GC genomes A is the most dominant base in the first codon positions. But purine bases, i.e., (A + G), predominantly occur in the first codon position. In the second codon position, A is the most dominant base in most of the organisms and G is the least dominant base in all the organisms. There is no unique regular pattern of individual bases at the third codon positions; however, there are significant differences in the occurrences of (G + C) contents in the third codon positions among the different organisms. Calculations of dinucleotide frequencies in 12 different organisms indicate that in GC-rich genomes GG, GC, CC, and CG dinucleotides are the most dominant whereas the reverse is true in case of low-GC genomes. Biological implications of these results are discussed in this paper.

Bacteria↗

PubMed2002

Mutational equilibrium model of genome size evolution.

The paper describes a mutational equilibrium model of genome size evolution. This model is different from both adaptive and junk DNA models of genome size evolution in that it does not assume that genome size is maintained either by positive or stabilizing selection for the optimum genome size (as in adaptive theories) or by purifying selection against too much junk DNA (as in junk DNA theories). Instead the genome size is suggested to evolve until the loss of DNA through more frequent small deletions is equal to the rate of DNA gain through more frequent long insertions. The empirical basis for this theory is the finding of a strong correlation and of a clear power-function relationship between the rate of mutational DNA loss (per bp) through small deletions and genome size in animals. Genome size scales as a negative 1.3 power function of the deletion rate per nucleotide. Such a relationship is not predicted by either adaptive or junk DNA theories. However, if genome size is maintained at equilibrium by the balance of mutational forces, this empirilical relationship can be readily accommodated. Within this framework, this finding would imply that the rate of DNA gain through large insertions scales up a quarter-power function of genome size. On this view, as genome size grows, the rate of growth through large insertions is increasing as a quarter power function of genome size and the rate of DNA loss through small deletions increases linearly, until eventually, at the stable equilibrium genome size value, rates of growth and loss equal each other. The current data also suggest that the long-term variation is genome size in animals is brought about to a significant extent by changes in the intrinsic rates of DNA loss through small deletions. Both the origin of mutational biases and the adaptive consequences of such a mode of evolution of genome size are discussed.

Base Sequence↗