Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Paralogous Genes”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources
PubMedDate not supplied

Developmental gene control of brainstem function: views from the embryo.

The respiratory rhythm is generated within the hindbrain reticular formation, rostrally in the vicinity of the facial nucleus and caudally within the vagal/glossopharyngeal domain. This is probably one of the best models to understand how genes have been selected and conserved to control adaptive behaviour in vertebrates. The para-facial region is well understood with respect to the transcription factors that underlie antero-posterior specification of neural progenitors in the embryo. Hox paralogs and Hox-regulating genes kreisler and Krox-20 govern transient formation of developmental compartments, the rhombomeres, in which rhythmic neuronal networks develop. Hox are master genes selecting and coordinating the developmental fate of reticular and motor neurons thereby specifying patterns of motor activities operating throughout life. Neuronal function and development are also tightly linked in the vagal/glossopharyngeal domain. At this level, bdnf acts as a neurotrophin of peripheral chemoafferent neural populations and as a neuromodulator of the central rhythmogenic respiratory circuits. A general view is now emerging on the role of developmental transcription and trophic factors allowing the coordinated integration of different neuronal types to produce, and eventually refine, respiratory rhythmic pattern in a use-dependent manner.

Animals↗
PubMed2004

Position-specific expression of Hox genes along the gastrointestinal tract.

Hox genes play a critical role in morphogenesis of the early embryo along the anteroposterior axis. In mammals, 39 Hox genes with extensive homology are organized into 13 paralogous groups, forming four clusters on four separate chromosomes. The genes within each cluster are arranged in a 3' to 5' direction and expressed in a temporally and spatially coordinated manner along the anteroposterior axis in the vertebrae, limbs and viscera, including the gastrointestinal tract, but little is known about their spatial expression in the adult gastrointestinal tract. We used the quantitative polymerase chain reaction (PCR) intercalater method with SYBR Green to quantify human Hox gene expression in the adult gastrointestinal tract tissue: esophagus, stomach, duodenum, jejunum, ileum, ileocecum, cecum, ascending colon, transverse colon, descending colon and rectum. Hox gene expression was normalized to glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) gene expression. The spatial expression pattern was analyzed by the multivariate method. The expression level of all 39 Hox genes could be measured in a reproducible manner. Genes with higher expression in the foregut-derived segments tended to have lower expression in hindgut-derived segments, whereas those with low expression in the former tended to have higher in the latter. Principal components analysis and permax analysis revealed a position-specific expression pattern of Hox genes along the anteroposterior axis of the adult gastrointestinal tract. The pattern recapitulates the expression pattern in the embryonic gastrointestinal tract. We suggest that Hox genes may play a pivotal role in the position-specific regenerative process of intestinal epithelial cells.

Chromatography, High Pressure Liquid↗
PubMed2005

The broad-spectrum blast resistance gene Pi9 encodes a nucleotide-binding site-leucine-rich repeat protein and is a member of a multigene family in rice.

The broad-spectrum rice blast resistance gene Pi9 was cloned using a map-based cloning strategy. Sequencing of a 76-kb bacterial artificial chromosome (BAC) contig spanning the Pi9 locus led to identification of six tandemly arranged resistance-like genes with a nucleotide-binding site (NBS) and leucine-rich repeats (LRRs) (Nbs1-Pi9-Nbs6-Pi9). Analysis of selected Pi9 deletion mutants and transformation of a 45-kb fragment from the BAC contig into the susceptible rice cultivar TP309 narrowed down Pi9 to the candidate genes Nbs2-Pi9 and Nbs3-Pi9. Disease evaluation of the transgenic lines carrying the individual candidate genes confirmed that Nbs2-Pi9 is the Pi9 gene. Sequence comparison analysis revealed that the six paralogs at the Pi9 locus belong to four classes and gene duplication might be one of the major evolutionary forces contributing to the formation of the NBS-LRR gene cluster. Semiquantitative reverse transcriptase (RT)-PCR analysis showed that Pi9 was constitutively expressed in the Pi9-resistant plants and was not induced by blast infection. The cloned Pi9 gene provides a starting point to elucidate the molecular basis of the broad-spectrum disease resistance and the evolutionary mechanisms of blast resistance gene clusters in rice.

Amino Acid Sequence↗
PubMed2005

Conditional expression of the CTCF-paralogous transcriptional factor BORIS in normal cells results in demethylation and derepression of MAGE-A1 and reactivation of other cancer-testis genes.

Brother of the Regulator of Imprinted Sites (BORIS) is a mammalian CTCF paralog with the same central 11Zn fingers (11ZF) that mediate specific interactions with varying approximately 50-bp target sites. Regulated in vivo occupancy of such sites may yield structurally and functionally distinct CTCF/DNA complexes involved in various aspects of gene regulation, including epigenetic control of gene imprinting and X chromosome inactivation. The latter functions are mediated by meCpG-sensitive 11ZF binding. Because CTCF is normally present in all somatic cells, whereas BORIS is active only in CTCF- and 5-methylcytosine-deficient adult male germ cells, switching DNA occupancy from CTCF to BORIS was suggested to regulate site specificity and timing of epigenetic reprogramming. In addition to 11ZF-binding paternal imprinting control regions, cancer-testis gene promoters also undergo remethylation during CTCF/BORIS switching in germ cells. Only promoters of cancer testis genes are normally silenced in all somatic cells but activated during spermatogenesis when demethylated in BORIS-positive germ cells and are found aberrantly derepressed in various tumors. We show here that BORIS is also expressed in multiple cancers and is thus itself a cancer-testis gene and that conditional expression of BORIS in normal fibroblasts activates cancer-testis genes selectively. We tested if replacement of CTCF by BORIS on regulatory DNA occurs in vivo on activation of a prototype cancer-testis gene, MAGE-A1. Transition from a hypermethylated/silenced to a hypomethylated/activated status induced in normal cells by 5-aza-2'-deoxycytidine (5-azadC) was mimicked by conditional input of BORIS and is associated with complete switching from CTCF to BORIS occupancy at a single 11ZF target. This site manifested a novel type of CTCF/BORIS 11ZF binding insensitive to CpG methylation. Whereas 5-azadC induction of BORIS takes only few hours, derepression of MAGE-A1 occurred 1 to 2 days later, suggesting that BORIS mediates cancer-testis gene activation by 5-azadC. Indeed, infection of normal fibroblasts with anti-BORIS short hairpin RNA retroviruses before treatment with 5-azadC blocked reactivation of MAGE-A1. We suggest that BORIS is likely tethering epigenetic machinery to a novel class of CTCF/BORIS 11ZF target sequences that mediate induction of cancer-testis genes.

Animals↗
PubMed2003

Numerous groups of chromosomal regional paralogies strongly indicate two genome doublings at the root of the vertebrates.

The appearance of the vertebrates demarcates some of the most far-reaching changes of structure and function seen during the evolution of the metazoans. These drastic changes of body plan and expansion of the central nervous system among other organs coincide with increased gene numbers. The presence of several groups of paralogous chromosomal regions in the human genome is a reflection of this increase. The simplest explanation for the existence of these paralogies would be two genome doublings with subsequent silencing of many genes. It is argued that gene localization data and the delineation of paralogous chromosomal regions give more reliable information about these types of events than dendrograms of gene families as gene relationships are often obscured by uneven replacement rates as well as other factors. Furthermore, the topographical relations of some paralogy groups are discussed.

Animals↗
PubMed2005

The HOX gene cluster in the bivalve mollusc Mytilus galloprovincialis.

The clustered Hox genes play a central role in the regulation of development in bilaterian animals. In this study, we analyzed the homeobox-containing genes in a bivalve mollusc, the mussel Mytilus galloprovincialis, an unsegmented spiralian lophotrochozoan. We isolated and characterized four Hox cluster genes using the polymerase chain reaction with specific primers. Molecular alignments and phylogenetic analysis indicate that these mussel genes are homologs of the anterior group (pb ortholog), paralog group 3, and central group (PG4/Dfd and PG5/Scr) genes. The putative homeodomain sequences were designated Mgox1, Mgox2, Mgox3, and Mgox4.

Amino Acid Sequence↗
PubMed2006

A revised evolutionary history of the CYP1A subfamily: gene duplication, gene conversion, and positive selection.

Members of cytochrome P450 subfamily 1A (CYP1As) are involved in detoxification and bioactivation of common environmental pollutants. Understanding the functional evolution of these genes is essential to predicting and interpreting species differences in sensitivity to toxicity caused by such chemicals. The CYP1A gene subfamily comprises a single ancestral representative in most fish species and two paralogs in higher vertebrates, including birds and mammals. Phylogenetic analysis of complete coding sequences suggests that mammalian and bird paralog pairs (CYP1A1/2 and CYP1A4/5, respectively) are the result of independent gene duplication events. However, comparison of vertebrate genome sequences revealed that CYP1A genes lie within an extended region of conserved fine-scale synteny, suggesting that avian and mammalian CYP1A paralogs share a common genomic history. Algorithms designed to detect recombination between nucleotide sequences indicate that gene conversion has homogenized most of the length of the chicken CYP1A genes, as well as the 5' end of mammalian CYP1As. Together, these data indicate that avian and mammalian CYP1A paralog pairs resulted from a single gene duplication event and that extensive gene conversion is responsible for the exceptionally high degree of sequence similarity between CYP1A4 and CYP1A5. Elevated nonsynonymous/synonymous substitution ratios within a putatively unconverted stretch of approximately 250 bp suggests that positive selection may have reduced the effective rate of gene conversion in this region, which contains two substrate recognition sites. This work significantly alters our understanding of functional evolution in the CYP1A subfamily, suggesting that gene conversion and positive selection have been the dominant processes of sequence evolution.

Animals↗
PubMed2006

INVHOGEN: a database of homologous invertebrate genes.

Classification of proteins into families of homologous sequences constitutes the basis of functional analysis or of evolutionary studies. Here we present INVertebrate HOmologous GENes (INVHOGEN), a database combining the available invertebrate protein genes from UniProt (consisting of Swiss-Prot and TrEMBL) into gene families. For each family INVHOGEN provides a multiple protein alignment, a maximum likelihood based phylogenetic tree and taxonomic information about the sequences. It is possible to download the corresponding GenBank flatfiles, the alignment and the tree in Newick format. Sequences and related information have been structured in an ACNUC database under a client/server architecture. Thus, complex selections can be performed. An external graphical tool (FamFetch) allows access to the data to evaluate homology relationships between genes and distinguish orthologous from paralogous sequences. Thus, INVHOGEN complements the well-known HOVERGEN database. The databank is available at http://www.bi.uni-duesseldorf.de/~invhogen/invhogen.html.

Animals↗
PubMed2004

Analysis of sequence, map position, and gene expression reveals conserved essential genes for iron uptake in Arabidopsis and tomato.

Arabidopsis (Arabidopsis thaliana) and tomato (Lycopersicon esculentum) show similar physiological responses to iron deficiency, suggesting that homologous genes are involved. Essential gene functions are generally considered to be carried out by orthologs that have remained conserved in sequence and map position in evolutionarily related species. This assumption has not yet been proven for plant genomes that underwent large genome rearrangements. We addressed this question in an attempt to deduce functional gene pairs for iron reduction, iron transport, and iron regulation between Arabidopsis and tomato. Iron uptake processes are essential for plant growth. We investigated iron uptake gene pairs from tomato and Arabidopsis, namely sequence, conserved gene content of the regions containing iron uptake homologs based on conserved orthologous set marker analysis, gene expression patterns, and, in two cases, genetic data. Compared to tomato, the Arabidopsis genome revealed more and larger gene families coding for the iron uptake functions. The number of possible homologous pairs was reduced if functional expression data were taken into account in addition to sequence and map position. We predict novel homologous as well as partially redundant functions of ferric reductase-like and iron-regulated transporter-like genes in Arabidopsis and tomato. Arabidopsis nicotianamine synthase genes encode a partially redundant family. In this study, Arabidopsis gene redundancy generally reflected the presumed genome duplication structure. In some cases, statistical analysis of conserved gene regions between tomato and Arabidopsis suggested a common evolutionary origin. Although involvement of conserved genes in iron uptake was found, these essential genes seem to be of paralogous rather than orthologous origin in tomato and Arabidopsis.

Amino Acid Sequence↗
PubMed2006

The amphibian globin gene repertoire as revealed by the Xenopus genome.

The draft genome sequence of the Western clawed frog Xenopus (Silurana) tropicalis facilitates the identification, expression analysis and phylogenetic classification of the amphibian globin gene repertoire. Frog and mammalian neuroglobin display about 67% protein sequence identity, with the expected predominant expression in frog brain and eye. Frog and mammalian cytoglobins share about 69% of their amino acids, but the frog protein lacks the mammalian-type extension at the C-terminus. Like in mammals, X. tropicalis cytoglobin is expressed in many organs including neural tissue. Neuroglobin and cytoglobin genomic regions are syntenically conserved in all vertebrate classes. Frog and fish globin X show only 57% amino acid identity, but gene synteny analysis confirms orthology. The expression pattern of X. laevis globin X differs from that in fish, with a prominent expression in the eye and weak expression in most other examined tissues. Globin X is possibly present as two paralogous copies in X. tropicalis, with one copy showing transition stages of non-functionalization. The amphibian genome contains a previously unknown globin type (tentatively named 'globin Y') which is expressed in a broad range of tissues and is distantly related to the cytoglobin lineage. The globin Y gene is linked to a cluster of larval and adult hemoglobin alpha and beta genes which contains substantially more paralogous hemoglobin gene copies than previously published. Database and gene synteny analyses confirm the absence of a myoglobin gene in X. tropicalis.

Algorithms↗
PubMed1996

Homeobox genes and male reproductive development.

PURPOSE: Homeobox genes encode transcription factors that dictate developmental events in philogenetically diverse organisms. In comparison to what is known about their role in embryogenesis, we know very little concerning homeobox gene function in neonates or adults. In this communication, we review studies that address the possible role of homeobox genes in male reproductive development, a system active in neonate and adult animals. METHODS: Studies have shown that many homeobox genes are expressed in germ cells of the testis, while less is known about the identity of homeobox genes expressed in somatic cells of the testis or epididymis. Hox homeobox genes display a pattern of expression in testis that is dependent on their paralogous and orthologous position within the Hox gene chromosome clusters. Other homeobox genes are expressed in the male reproductive system, including many POU and Prd/Pax homeobox gene family members. More recently, it has been shown that the orphan homeobox gene, Pem, originally isolated by subtraction hybridization on the basis of its differential expression in tumor cell lines, is selectively expressed in reproductive tissue. Alternatively spliced Pem transcripts accumulate in testis and epididymis that differ from those expressed in tumors and placenta. Pem transcripts accumulate postnatally in the epididymis in a developmentally regulated manner. CONCLUSIONS: The highly regulated pattern of expression exhibited by many homeobox genes in the male reproductive system suggests that homeobox transcription factors may dictate developmental events in this system. However, future studies are needed to determine the specific functional roles homeobox genes in male reproductive development and spermatogenesis.

Adult↗
PubMed2000

Phylogeny and divergence times in Pinaceae: evidence from three genomes.

In Pinaceae, the chloroplast, mitochondrial, and nuclear genomes are paternally, maternally, and biparentally inherited, respectively. Examining congruence and incongruence of gene phylogenies among the three genomes should provide insights into phylogenetic relationships within the family. Here we studied intergeneric relationships of Pinaceae using sequences of the chloroplast matK gene, the mitochondrial nad5 gene, and the low-copy nuclear gene 4CL. The 4CL gene may exist as a single copy in some species of Pinaceae, but it constitutes a small gene family with two or three members in others. Duplication and deletion of the 4CL gene occurred at a tempo such that paralogous loci are maintained within but not between genera. Exons of the 4CL gene have diverged approximately twice as fast as the matK gene and five times more rapidly than the nad5 gene. The partition-homogeneity test indicates that the three data sets are homogeneous. A combined analysis of the three gene sequences generated a well-resolved and strongly supported phylogeny. The combined phylogeny, which is topologically congruent with the three individual gene trees based on the Templeton test, is likely to represent the organismal phylogeny of Pinaceae. This phylogeny agrees to a certain extent with previous phylogenetic hypotheses based on morphological, anatomical, and immunological data. Disagreement between the previous hypotheses and the three-genome phylogeny suggests that morphology of both vegetative and reproductive organs has undergone convergent evolution within the pine family. The strongly supported monophyly of Nothotsuga longibracteata, Tsuga mertensiana, and Tsuga canadensis on all three gene phylogenies provides evidence against previous hypotheses of intergeneric hybrid origins of N. longibracteata and T. mertensiana. Divergence times of the genera were estimated based on sequence divergence of the matK gene, and they correspond well with the fossil record.

Cell Nucleus↗
PubMed2005

Aryl hydrocarbon receptors in the frog Xenopus laevis: two AhR1 paralogs exhibit low affinity for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent developmental toxicant in most vertebrates. However, frogs are relatively insensitive to TCDD toxicity, especially during early life stages. Toxicity of TCDD and related halogenated aromatic hydrocarbons is mediated by the aryl hydrocarbon receptor (AhR), and specific differences in properties of the AhR signaling pathway can underlie in TCDD toxicity in different species. This study investigated the role of AhR in frog TCDD insensitivity, using Xenopus laevis as a model system. X. laevis, a pseudotetraploid species, expresses two distinct AhR1 genes, AhR1alpha and AhR1beta. Sharing 86% amino acid identity, these likely represent distinct genes, both orthologous to mammalian AhR and paralogous to the AhR2 gene(s) in most fish. Both AhR1alpha and AhR1beta exhibit TCDD-dependent binding of cognate DNA sequences, but they bind TCDD with at least 20-fold lower affinity than the mouse AhR(b-1) protein, and they are similarly less responsive in TCDD-induced reporter gene induction in conjunction with the mouse CYP1A1 promoter. Furthermore, CYP1A6 and CYP1A7 induction by TCDD in cultured X. laevis A6 cells appears much less responsive than CYP1A induction in cell lines derived from more sensitive animals. Taken together, these data suggest that low affinity binding by X. laevis AhRs plays an important mechanistic role in the insensitivity of frogs to TCDD. An understanding of these molecular mechanisms should aid amphibian ecotoxicology and refine the use of frog embryos as a model [e.g. in FETAX (Frog Embryo Teratogenesis Assay-Xenopus)] for determining developmental toxicity of samples containing dioxin-like compounds.

Abnormalities, Drug-Induced↗
PubMed2005

Direct activation of genes involved in intracellular iron use by the yeast iron-responsive transcription factor Aft2 without its paralog Aft1.

The yeast Saccharomyces cerevisiae contains a pair of paralogous iron-responsive transcription activators, Aft1 and Aft2. Aft1 activates the cell surface iron uptake systems in iron depletion, while the role of Aft2 remains poorly understood. This study compares the functions of Aft1 and Aft2 in regulating the transcription of genes involved in iron homeostasis, with reference to the presence/absence of the paralog. Cluster analysis of DNA microarray data identified the classes of genes regulated by Aft1 or Aft2, or both. Aft2 activates the transcription of genes involved in intracellular iron use in the absence of Aft1. Northern blot analyses, combined with chromatin immunoprecipitation experiments on selected genes from each class, demonstrated that Aft2 directly activates the genes SMF3 and MRS4 involved in mitochondrial and vacuolar iron homeostasis, while Aft1 does not. Computer analysis found different cis-regulatory elements for Aft1 and Aft2, and transcription analysis using variants of the FET3 promoter indicated that Aft1 is more specific for the canonical iron-responsive element TGCACCC than is Aft2. Finally, the absence of either Aft1 or Aft2 showed an iron-dependent increase in the amount of the remaining paralog. This may provide additional control of cellular iron homeostasis.

Cation Transport Proteins↗
PubMed2006

Varying signals of the effects of natural selection during teleost growth hormone gene evolution.

The growth hormone (GH) gene of teleost fish exhibits a higher degree of variability compared with other vertebrate groups. However, the different selective constraints at the sequence level are not well understood. In this study, maximum-likelihood (ML) models of codon substitutions were used to investigate Darwinian adaptive evolution of the GH gene in teleost fishes. Complete GH gene sequences of 54 fish species were classified into 4 orders, and the variable nature of GH was examined by determining the dN and dS rate variation and the rates of molecular evolution for each teleost order. The results indicate that although the overall evolution rate for teleost GH is high ((1.15 +/- 0.01) x 10(-9) substitutions/(aa site x y)) compared with the "slow phases" in mammals ((0.21 to 0.28 +/- 0.05) x 10(-9)), the vital structure of this gene has been retained. While the majority of the amino acid changes appear to be due to relaxation of purifying selection, some positively selected sites were detected in regions with no specifically identified role in protein function. The positively selected regions observed in salmoniformes lineage suggests a possible role for positive selection driving functional divergence in paralogous forms of the GH gene after whole-genome duplication in this lineage.

Amino Acid Sequence↗
PubMed2026

Evolutionary adaptation of CCD4 enzymes in Buddleja alternifolia for crocetin biosynthesis.

INTRODUCTION: Carotenoid cleavage dioxygenase 4 (CCD4) enzymes play central roles in carotenoid turnover and apocarotenoid biosynthesis in plants. Despite their importance, the evolutionary mechanisms underlying diversification of CCD4 catalytic functions remain poorly understood. This study investigated the CCD gene family in Buddleja alternifolia, with particular emphasis on the expansion and functional evolution of the CCD4 subfamily. METHODS: A genome-wide identification and comparative analysis of CCD genes were performed in B. alternifolia. Genomic organization, phylogenetic relationships, and syntenic patterns were analyzed to investigate gene family expansion. Functional characterization of 11 BaCCD4 paralogs was conducted through biochemical assays, while structural analyses were used to identify sequence features associated with differences in substrate cleavage specificity. Gene expression profiling was performed to assess patterns of tissue-specific regulation. RESULTS: Twenty-three CCD genes were identified, including 12 CCD4 paralogs, representing one of the largest CCD4 expansions reported within Lamiales. Syntenic and genomic analyses revealed that recent tandem duplication events, particularly within a CCD4-rich region on chromosome 10, were the primary drivers of this expansion. The presence of pseudogenes in the same region supported an ongoing birth-and-death evolutionary process. Functional analyses demonstrated extensive biochemical diversification among BaCCD4 enzymes despite their high sequence similarity. Several paralogs catalyzed asymmetric carotenoid cleavage leading to citraurin production, whereas two paralogs, KAG8367281 and KAG8375220, exhibited symmetric zeaxanthin cleavage activity, producing crocetin dialdehyde, the direct precursor of crocins. Notably, these crocetin-producing enzymes belonged to closely related paralogous pairs whose counterparts displayed distinct cleavage specificities, indicating rapid neofunctionalization after duplication. Structural analyses suggested that subtle sequence variations, including indels affecting loop regions adjacent to the substrate access channel, may underlie changes in regioselectivity. Expression profiling further revealed tissue-specific expression patterns consistent with functional divergence among paralogs. DISCUSSION: These findings indicate that crocetin-forming activity in B. alternifolia likely evolved through progressive modifications of ancestral CCD4 functions rather than through a single evolutionary event. The remarkable expansion and diversification of the CCD4 subfamily provide evidence for the role of gene duplication and neofunctionalization in shaping carotenoid cleavage specificity. Collectively, this work establishes B. alternifolia as a valuable model for investigating the molecular evolution of CCD4 enzymes and the emergence of specialized apocarotenoid metabolism in plants.

CCD4 evolution↗
PubMed2026

Single-allele chromatin tracing reveals cytokine-dependent super-enhancer repositioning in CD4+ T cells.

Naive CD4+ T cells interpret cytokine cues to commit to T helper lineages. Here, we examined the impact of cytokines on the Ets1-Fli1 locus, which encodes paralogous transcription factors essential for T cell effector responses. Epigenomic and chromatin interaction profiling in double-positive (DP) thymocytes defined a T cell super-enhancer and a CTCF-bound boundary. Chromatin tracing at single-allele resolution revealed concurrent multi-way interactions among Ets1, Fli1, and the super-enhancer coupled to transcription. Deleting the CTCF boundary decompacted the locus without altering Ets1 expression or T cell development, whereas deleting the super-enhancer drew Ets1 and Fli1 closer; promoter proximity increased Ets1-Fli1 co-expression. In CD4+ Th1 cells, cytokines increased multi-way interactions and repositioned the super-enhancer toward the geometric center, activating both paralogs. Super-enhancer deletion rendered Th1 cells structurally and transcriptionally DP like. Thus, cytokines can drive lineage-specific gene activation by repositioning a super-enhancer, providing a mechanistic framework for how noncoding variants at the Ets1-Fli1 locus contribute to CD4+ T cell-mediated immune disorders.

Animals↗
PubMed2005

Genome trees and the nature of genome evolution.

Genome trees are a means to capture the overwhelming amount of phylogenetic information that is present in genomes. Different formalisms have been introduced to reconstruct genome trees on the basis of various aspects of the genome. On the basis of these aspects, we separate genome trees into five classes: (a) alignment-free trees based on statistic properties of the genome, (b) gene content trees based on the presence and absence of genes, (c) trees based on chromosomal gene order, (d) trees based on average sequence similarity, and (e) phylogenomics-based genome trees. Despite their recent development, genome tree methods have already had some impact on the phylogenetic classification of bacterial species. However, their main impact so far has been on our understanding of the nature of genome evolution and the role of horizontal gene transfer therein. An ideal genome tree method should be capable of using all gene families, including those containing paralogs, in a phylogenomics framework capitalizing on existing methods in conventional phylogenetic reconstruction. We expect such sophisticated methods to help us resolve the branching order between the main bacterial phyla.

Evolution, Molecular↗