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PubMed2005

[Genomics and evolution of cellular organelles].

The structure, functions, and evolution of cellular organelles are reviewed. The mitochondrial genomes of eukaryotes differ considerably in size and structural organization mainly due to the length variation in noncoding regions and the presence of introns. The mitochondrial genomes of angiosperms are the largest and most complicated. Gene content in eukaryotic mitochondrial genomes is similar. They usually encode all types of rRNA, a complete or partial complement of tRNA, and a limited number of proteins essential for mitochondrial functions. In all eukaryotes studied, mitochondrial genomes code for two highly hydrophobic proteins involved in respiration, cytochrome b and subunit 1 of cytochrome oxidase. Genome structure and gene content in plastids, mainly in higher plant chloroplasts, are highly conserved. Plastid genomes of algae are more variable in gene composition and contain several unique genes absent in the chloroplast DNA of higher plants. Plastid genomes encode proteins involved in transcription and translation, as well as proteins of the photosynthetic apparatus. Both types of cellular organelles are supposed to be of endosymbiotic origin. Modern plastids originate from a cyanobacterial ancestor. Alpha-proteobacteria, especially the most mitochondrion-like rickettsia, gave rise to mitochondria. The origin of plastids of higher plants and green algae as a result of primary endosymbiosis and that of other algal lineages by secondary endosymbiosis are briefly discussed.

Animals↗
PubMed2004

Cloning, genomic organization, expression, and effect on beta-casein promoter activity of a novel isoform of the mouse Oct-1 transcription factor.

The ubiquitously expressed transcription factor Oct-1, a member of the POU domain factors, is involved in the regulation of expression of many tissue-specific and house-keeping genes. Multiple alternatively spliced isoforms of Oct-1 have been identified in human and mouse cells. The expression patterns of these isoforms and the analysis of their genomic organization and structure have suggested that the structural variation of Oct-1 isoforms may be important in conferring target and tissue specificity to its transcriptional activity. In this study, we have cloned and sequenced a new mouse Oct-1 isoform, named mOct-1Z. This novel isoform differs markedly at the C-terminus from the previously identified Oct-1 isoforms A, B, and C. It is generated by alternative splicing from the Oct-1 gene and its transcript exhibits a frameshift followed by an early stop codon, thus, its predicted protein has a distinct, much shorter C-terminal tail. However, this truncated isoform could still effectively bind to a consensus Oct-1 motif oligonucleotide and, like Oct-1B, activated the basal promoter activity of the mouse beta-casein gene. Oct-1Z is another ubiquitously expressed Oct-1 isoform, its transcript being detected in all mouse tissues examined, including the mammary gland, liver, lung, kidney, spleen, small intestine mucosa, uterus, and ovary.

5' Flanking Region↗
PubMed2004

Association of extensive polymorphisms in the SLAM/CD2 gene cluster with murine lupus.

Susceptibility to autoimmunity in B6.Sle1b mice is associated with extensive polymorphisms between two divergent haplotypes of the SLAM/CD2 family of genes. The B6.Sle1b-derived SLAM/CD2 family haplotype is found in many other laboratory mouse strains but only causes autoimmunity in the context of the C57Bl/6 (B6) genome. Phenotypic analyses have revealed variations in the structure and expression of several members of the SLAM/CD2 family in T and B lymphocytes from B6.Sle1b mice. T lymphocytes from B6.Sle1b mice have modified signaling responses to stimulation at 4-6 weeks of age. While autoimmunity may be mediated by a combination of genes in the SLAM/CD2 family cluster, the strongest candidate is Ly108, a specific isoform of which is constitutively upregulated in B6.Sle1b lymphocytes.

Alleles↗
PubMed2001

Isolation and phylogenetic analysis of HERV-K long terminal repeat cDNA in cancer cells.

Long terminal repeat (LTR) elements of human endogenous retrovirus (HERV-K) may have contributed to disease-associated structural change or genetic variation in the human genome. The LTR elements have been found to be coexpressed with sequences of closely located genes. We identified seven HERV-K LTR elements from mRNA of human cancer cells (HepG2, MCF7, and SiHa), using the RT-PCR approach. Four of them are closely related to the human-specific HERV-K LTR elements with a high degree of sequence homology in a neighbor-joining phylogenetic tree. The data suggest that recently proliferated HERV-K LTR elements are expressed actively in various cancer cells. These HERV-K LTR elements deserve further investigation as potential leads in the treatment of human cancer.

Base Sequence↗
PubMed1999

Presence and phylogenetic analysis of HERV-K LTR on human X and Y chromosomes: evidence for recent proliferation.

The K group of human endogenous retroviruses (HERV-K) has been suggested to have a role in disease and has recently been shown to include long terminal repeat (LTR) elements that are human specific. Here we investigated the presence of HERV-K LTRs on the human X and Y chromosomes with the use of PCR on a monochromosomal somatic cell hybrid DNA panel. We report twelve such sequences on the X chromosome and ten sequences on the Y chromosome. Phylogenetic analysis reveals that clones X2, 4, 5, 6, 7, 11, 15 from the X chromosome and clones Y4, 5, 7, 10 from the Y chromosome are closely related to the human-specific members of Medstrand and Mager's cluster 9. The sequence of clone Y7 from the Y chromosome is identical with human-specific HERV-K LTR element (AC002350) from chromosome 12q24. The findings suggest recent proliferation and transposition of HERV-K LTR elements on these chromosomes. Such events may have contributed to structural change and genetic variation in the human genome. We draw attention to evolutionarily recent changes in homologies between X and Y chromosomes as a method of further investigating such transpositions.

DNA, Viral↗
PubMed2001

Phylogeny of SINE-R retroposons in Asian apes.

The SINE-R retroposon family was derived from the long terminal repeats (LTRs) of human endogenous retrovirus K (HERV-K) that had been active during the hominoid evolution. The retroposons and HERV-K LTR elements have potential relevance to structural change and genetic variation of the hominoid genome. In our previous study, we found that the SINE-R retroposons were hominoid specific. Here we identified seventeen new SINE-R retroposons (14 from orangutan and 3 from gibbon) from Asian apes and phylogenetically analysed them in comparison with those of the humans and African great apes. None of the retroposons from Asian apes were closely related to SINE-R.C2 that is human specific, and originally identified in the gene for the C2 component of complement, whereas some retroposons (Ch-M10, Ch-M16, Gor-M, Gor-F1, Gor-M6, and Gor-F9) from African great apes showed very close relationship with that of the SINE-R.C2 retroposon. The phylogenetic tree based on the SINE-R retroposons revealed wide overlap of the retroposons across species, suggesting that the SINE-R retroposons have been evolved parallel pattern in the course of hominoid evolution.

Animals↗
PubMed2026

Dissecting genetic architecture and improving machine learning‑based genomic prediction of flowering time in Osmanthus fragrans by integrating structural variants.

Sweet osmanthus (Osmanthus fragrans), a traditional ornamental plant in China, exhibits substantial variation in autumn flowering time, which significantly affects landscape application and cultivation efficiency. Here, we performed a genome-wide association study on 127 resequenced accessions classified into early, intermediate, and late flowering types, using a set of 2,325,410 single-nucleotide polymorphisms (SNPs) and 246,824 structural variants (SVs). By integrating SNP/insertion and deletion (Indel) and SV data with weighted gene co-expression network analysis, machine learning, and genomic prediction, we dissected the genetic architecture of flowering time. We identified 24 associated SNP/Indels and six SVs, mapping to 30 candidate genes, including known flowering regulators FLK, LOS1, Y14, MIF2, and GID1B. These genes showed tissue-specific expression, with some responding to low temperature. The two hub genes, GUX1 and LYG027904, were located within modules of the co-expression network associated with low-temperature treatment. Haplotype analysis revealed a specific three-SNP haplotype associated with late flowering and linked to LOS1, and epistatic interactions among combined genotypes contributed to phenotypic variation. Notably, integrating SVs with SNP/Indels improved genomic prediction accuracy; the gradient boosting decision tree model outperformed other machine learning algorithms, achieving a mean accuracy of 0.859 and an AUC > 0.8 (where AUC is area under receiver operating characteristic curve) for all flowering types. These findings provide insights into the genetic mechanisms underlying flowering time variation in O. fragrans, offer candidate genes and haplotypes for molecular breeding, and highlight the value of integrating SVs with machine learning for genomic prediction in woody ornamentals.

Machine Learning↗
PubMed2002

Comparative genomic analysis of equilibrative nucleoside transporters suggests conserved protein structure despite limited sequence identity.

Equilibrative nucleoside transporters (ENTs) are a recently characterized and poorly understood group of membrane proteins that are important in the uptake of endogenous nucleosides required for nucleic acid and nucleoside triphosphate synthesis. Despite their central importance in cellular metabolism and nucleoside analog chemotherapy, no human ENT gene has been described and nothing is known about gene structure and function. To gain insight into the ENT gene family, we used experimental and in silico comparative genomic approaches to identify ENT genes in three evolutionarily diverse organisms with completely (or almost completely) sequenced genomes, Homo sapiens, Caenorhabditis elegans and Drosophila melanogaster. We describe the chromosomal location, the predicted ENT gene structure and putative structural topologies of predicted ENT proteins derived from the open reading frames. Despite variations in genomic layout and limited ortholog protein sequence identity (< or =27.45%), predicted topologies of ENT proteins are strikingly similar, suggesting an evolutionary conservation of a prototypic structure. In addition, a similar distribution of protein domains on exons is apparent in all three taxa. These data demonstrate that comparative sequence analyses should be combined with other approaches (such as genomic and proteomic analyses) to fully understand structure, function and evolution of protein families.

Alternative Splicing↗
PubMed2026

A haploid wild yeast resource for exploring the natural ecology of Saccharomyces cerevisiae.

Saccharomyces cerevisiae occurs predominantly in the diploid state in nature, limiting genetic analyses of wild populations. Here, we establish a haploid collection from 32 Taiwanese S. cerevisiae isolates through targeted HO disruption. This resource spans predomesticated Asian wild lineages and enables the investigation of reproductive isolation and ecological trait variation. Although all pairwise hybridizations formed zygotes, many yielded reduced spore viability, revealing strong postzygotic barriers. Genome analyses associated reduced hybrid fertility with lineage-specific structural variation, including elevated levels of intra-chromosomal inversions in H413-8/TW1 and inter-chromosomal rearrangements in PD35A/CHN-V, rather than sequence divergence alone. Phenotyping revealed ecological differentiation, with TW1 favoring cooler growth and a natural hybrid exhibiting heterosis with expanded thermotolerance. Most wild strains grew poorly on maltose, whereas anthropogenic strains displayed enhanced utilization linked to MAL + regulatory alleles and maltose-specific transporters. Together, this haploid collection links structural variation and metabolic divergence to ecological and reproductive differentiation in wild S. cerevisiae.

Saccharomyces cerevisiae↗
PubMed2026

Comprehensive genomic and computational insights into Brucella suis: pan-genome analysis, evolutionary perspectives, and in-silico vaccine design.

BACKGROUND: Brucella suis is a zoonotic intracellular pathogen responsible for brucellosis, mainly in swine and humans. Although numerous genome sequences are publicly available, an integrative genomic analysis combining pan-genome architecture, structural organization, evolutionary relationships, and vaccine-associated targets remains limited. RESULTS: In this study, we analyzed 91 publicly available B.suis genomes to characterize their pan-genome composition and genomic structure. The pan-genome exhibited an open configuration, indicating continued genomic diversification. A total of 2,146 core genes were identified, representing conserved functions essential for species maintenance, while the accessory genome reflected strain-level variability. Phylogenetic reconstruction based on single-copy orthologs revealed distinct evolutionary clades among the strains. A complementary phylogenetic analysis of pan-genome gene presence-absence patterns further supported clade differentiation and highlighted variation in accessory gene repertoires. Comparative synteny and genome structural analyses demonstrated largely conserved chromosomal organization with localized rearrangements across strains. Screening of the core proteome identified 64 putative antigenic proteins with predicted surface localization and immunogenic properties. Additionally, resistance-associated determinants related to tetracycline and doxycycline were detected in one genome within the dataset. CONCLUSIONS: This comprehensive genomic analysis defines the pan-genome structure, evolutionary relationships, and genome organization of B.suis. The integration of core and pan-genome-based phylogenies provides complementary insights into strain diversification, while the identified conserved antigenic candidates offer a foundation for future experimental validation and rational vaccine development strategies.

Genome, Bacterial↗
PubMed2006

GC-Profile: a web-based tool for visualizing and analyzing the variation of GC content in genomic sequences.

In order to understand the evolution, structure and function of genomes, it is important to know the general compositional features of DNA sequences. Based on the quadratic divergence, a new segmentation algorithm to partition a given genome or DNA sequence into compositionally distinct domains has been put forward. With the aid of the technique of cumulative GC profile, the distribution of segmentation points can be displayed intuitively. We have therefore developed them into GC-Profile, an interactive web-based software system, which can be used to segment prokaryotic and eukaryotic genomes. GC-Profile provides a quantitative and qualitative view of genome organization. Based on the obtained results, the relationships between the G+C content and other genomic features, such as distributions of genes and CpG islands, can be analyzed in a perceivable manner. It shows that GC-Profile would be an appropriate starting point for analyzing the isochore structure of higher eukaryotic genomes, and an intuitive tool for identifying genomic islands in prokaryotic genomes. GC-Profile is freely available at the website http://tubic.tju.edu.cn/GC-Profile/. In addition, precompiled binaries, together with examples and documentation, can also be freely downloaded for a local execution.

Algorithms↗
PubMed2026

STK11 Mutations and Deletions Define an Aggressive Molecular Subgroup of Cervical Adenocarcinoma.

Cervical adenocarcinoma accounts for 15%-20% of cervical cancers and is associated with poorer survival and reduced response to screening and immunotherapy compared with squamous cell carcinoma (SCC). The genomic drivers underlying this molecular subgroup remain incompletely characterized. Whole-exome sequencing was performed on 302 invasive cervical cancers from Guatemala and Venezuela. Structural variation analysis was conducted using SNP-array and whole-genome sequencing data. Findings were replicated in more than 4600 additional cervical cancer samples from TCGA, AACR Project GENIE, MSKCC, and Caris datasets. TP53 mutations were more frequent in adenocarcinoma than SCC, particularly in HPV-negative tumors. STK11 alterations, including mutations and focal deletions, were significantly enriched in HPV-positive adenocarcinomas compared with SCC and affected 23% of adenocarcinomas overall. Whole-genome analyses identified recurrent focal deletions, inversions, chromosomal rearrangements, and breakage-fusion-bridge events involving chromosome 19p and STK11 that were not detected by exome sequencing alone. STK11 alterations were associated with younger age at diagnosis, poorer overall survival, and inferior outcomes following immune checkpoint inhibitor (ICI) therapy. STK11 alterations significantly co-occurred with YAP1 amplification but were largely mutually exclusive with PIK3CA mutation. Cervical adenocarcinomas also demonstrated significantly lower CD274 (PD-L1) expression than SCC. STK11 alterations define a distinct molecular subgroup of cervical adenocarcinoma characterized by structural disruption of chromosome 19p, younger age at onset, and poorer clinical outcomes. These findings have implications for molecular classification and future targeted therapeutic approaches in cervical cancer.

Humans↗
PubMed2001

Novel immune-type receptor genes.

Novel immune-type receptor (NITR) genes, which initially were identified in the Southern pufferfish (Spheroides nephelus), encode products which consist of an extracellular variable (V) and V-like C2 (V/C2) domain, a transmembrane region, and a cytoplasmic tail, which typically possesses an immunoreceptor tyrosine-based inhibition motif (ITIM). Multiple NITR genes have been identified in close, contiguous chromosomal linkage. The V regions of NITRs resemble prototypic forms defined for immunoglobulin (Ig) and T-cell antigen receptor (TCR), are present in multiple families and exhibit regionalized variation in sequence, which also occurs in Ig and TCR. Comparisons of exons encoding transmembrane and cytoplasmic regions of multiple NITRs suggest that exon shuffling has factored in the diversification of the NITR gene complex. Zebrafish (Danio rerio) NITRs exhibit many of these characteristics. NITRs that have been identified in additional species of bony fish demonstrate additional variation in the number of extracellular domains as well as in the presence of intramembranous charged residues, cytoplasmic tails and ITIMs. The presence in NITRs of V regions that are related closely to those found in Ig and TCR, as well as regulatory motifs and other structural features that are characteristic of immune inhibitory receptors encoded at the leukocyte receptor cluster, suggests that the NITRs are representative of an integral stage in the evolution of innate and adaptive immune function.

Animals↗
PubMed2026

Panmixia in a Widespread Butterfly: High Dispersal and Ecological Generalism Buffer Against Landscape Fragmentation.

Habitat fragmentation is widely expected to reduce population connectivity and increase genetic differentiation, although the strength of these effects depends on species-specific traits such as dispersal ability. Here, we investigated the population genetic structure of the cosmopolitan butterfly, Pieris rapae L. (Lepidoptera: Pieridae), across western Germany using genome-wide single-nucleotide polymorphism (SNP) data. To analyze the effects of landscape structure on genetic connectivity, we applied a paired study design comprising four landscape pairs, each consisting of a highly intensified, modern agricultural landscape and a more heterogeneous, traditional landscape. Our results revealed no evidence of genetic differentiation. Pairwise FST values were close to zero; we detected no isolation by distance, and clustering analyses supported a single genetic population. No meaningful associations between genetic variation and environmental variables were detected, with landscape effects explaining less than 0.4% of genomic variation. Consequently, we found no evidence for stronger genetic structuring in modern compared to more connected traditional landscapes. Our results suggest that extensive habitat fragmentation does not necessarily translate into reduced genetic connectivity in highly mobile, generalist species. In P. rapae , high dispersal ability and ecological generalism appear to buffer against the genetic consequences of landscape modification, resulting in panmictic population structure even across strongly contrasting agricultural landscapes.

Pieris rapae↗
PubMed1996

MITOMAP: a human mitochondrial genome database.

We have developed a comprehensive database (MITOMAP) for the human mitochondrial DNA (mtDNA), the first component of the human genome to be completely sequenced [Anderson et al. (1981) Nature 290, 457-465]. MITOMAP uses the mtDNA sequence as the unifying element for bringing together information on mitochondrial genome structure and function, pathogenic mutations and their clinical characteristics, population associated variation, and gene- gene interactions. As increasingly larger regions of the human genome are sequenced and characterized, the need for integrating such information will grow. Consequently, MITOMAP not only provides a valuable reference for the mitochondrial biologist, it may also provide a model for the development of information storage and retrieval systems for other components of the human genome.

Amino Acid Sequence↗
PubMed2006

A new perspective on isochore evolution.

The genomes of mammals and birds show dramatic variation in base composition over large scales, the so called isochore structure of the genome. The origin of isochores is still controversial: various neutral and selectionist models have been proposed--and criticized--since the discovery of isochores in the 1970s. The availability of complete mammalian genomes has yielded new opportunities for addressing this question. In particular, it was recently proposed that (i) the isochore structure is declining in many mammalian groups, and that (ii) GC-content is influenced by local recombination rate, possibly via the mechanism of GC-biased gene conversion. In this article we review the existing support for these two hypotheses, and discuss how they can be combined to provide a new perspective on isochore evolution.

Animals↗
PubMed2006

Understanding the rise of the superbug: investigation of the evolution and genomic variation of Staphylococcus aureus.

The bacterium Staphylococcus aureus is a common cause of human infection, and it is becoming increasingly virulent and resistant to antibiotics. Our understanding of the evolution of this species has been greatly enhanced by the recent sequencing of the genomes of seven strains of S. aureus. Comparative genomic analysis allows us to identify variation in the chromosomes and understand the mechanisms by which this versatile bacterium has accumulated diversity within its genome structure.

Drug Resistance↗
PubMed1997

MITOMAP: an update on the status of the human mitochondrial genome database.

We have continued to develop MITOMAP, a comprehensive database for the human mitochondrial DNA (mtDNA). MITOMAP uses the mtDNA sequence as the unifying element for bringing together information on mitochondrial genome structure and function, pathogenic mutations and their clinical characteristics, population associated variation and gene-gene interactions. As increasingly larger regions of the human genome are sequenced and characterized, the need for integrating such information will grow. Consequently, MITOMAP not only provides a valuable reference for the mitochondrial biologist, it will also provide a model for the development of comprehensive, multi-media information storage and retrieval systems for other components of the human genome. This paper is an update of the changes which have occurred to MITOMAP over the past year.

Base Sequence↗