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Evolutionary conservation of a genetic pathway of programmed cell death.

Genetic analysis of programmed cell death in Caenorhabditis elegans has led to the identification of 13 genes that constitute a developmental pathway of programmed cell death. Two of the three key genes in this pathway, ced-9, a cell death suppressor, and ced-3, a cell death inducer, were found to encode proteins that share structural and functional similarities with the mammalian proto-oncogene product Bcl-2 and interleukin-1 beta converting enzyme, respectively. These results suggest that the genetic pathway of programmed cell death may be evolutionarily conserved from worms to mammals.

Animals↗

Utility of environmental primers targeting ancient enzymes: methylotroph detection in Lake Washington.

Methods have been explored for detection of methylotrophs in natural samples, using environmental primers based on genes involved in the tetrahydromethanopterin (H4MPT)-linked C1 transfer pathway. The underlying hypotheses were that the H4MPT-linked pathway is an ancient methylotrophy pathway, based on gene divergence, and that primers targeting more divergent genes will detect a broader variety of methylotrophs compared to the variety uncovered using probes and primers targeting highly conserved genes. Three groups of novel primer sets were developed targeting mch, mtdB, and fae, key genes in the H4MPT-linked pathway, and these were used to assess the variety of microorganisms possessing these genes in sediments from Lake Washington in Seattle, WA. Environmental clone libraries were constructed for each of the genes and were analyzed by RFLP, and representatives of different RFLP groups were sequenced and subjected to phylogenetic analysis. A combination of all three sets of novel primers allowed detection of the two previously characterized groups of methylotrophs in the site: methanotrophs of the (alpha- and the gamma-proteobacterial groups, belonghg to genera Methylosinus, Methylocystis, Methylomonas, Methylobacter, Methylomicrobium, and Methylococcus. In addition to the genes belonging to known methanotroph populations, novel genes were identified, suggesting existence of previously undetected microbial groups possessing C1 transfer functions in this site. These included sequences clustering with the well-characterized methylotrophic phyla, Methylobacterium, Hyphomicrobium, and Xanthobacter. In addition, sequences divergent from those known for any groups of methylotrophs or methanogens were obtained, suggesting the presence of a yet unidentified microbial group possessing this H4MPT-linked C1 transfer pathway.

Bacteria↗

Lipid metabolism mediated by adipocyte lipid binding protein (ALBP/aP2) gene expression in human THP-1 macrophages.

The critical initiating event in atherogenesis involves the invasion of monocytes through the endothelial wall of arteries, and their transformation from macrophages into foam cells. Human THP-1 monocytic cells can be induced to differentiate into macrophages by phorbol myristate acetate (PMA) treatment, and can then be converted into foam cells by exposure to oxidized low-density lipoprotein (oxLDL). We previously reported that adipocyte lipid binding protein (ALBP/aP2) is a gene that is highly up-regulated in foam cells in response to oxLDL. Here, we showed that overexpression of the ALBP gene using a lentiviral construct in macrophage foam cells enhanced the accumulations of cholesterol and triglyceride, probably due to an increased expression of the scavenger receptor type AI (SR-AI), which plays an important role in cell lipid metabolism. Moreover, we determined that the expression of acyl-coenzyme A: cholesterol-acyltransferase 1 (ACAT1) gene was up-regulated by the overexpression of ALBP gene, and on the other hand, the ATP-binding cassette A1 (ABCA1) gene and hormone sensitive lipase (HSL) gene, which mediate separately cholesterol efflux and cholesterol ester hydrolysis in the macrophage cells, were down-regulated by the overexpression of ALBP gene in these cells. Finally, our data indicated that oxLDL regulates expression of ALBP related to two peroxisome proliferator-responsive elements (PPREs) which are located in ALBP promoter region. These results have determined that ALBP gene expression accelerates cholesterol and triglyceride accumulation in macrophage foam cells and affects some key gene expression for lipid metabolism, suggesting some pivotal roles of ALBP in lipid metabolism for macrophage foam cell formation.

ATP Binding Cassette Transporter 1↗

Differences of gene expression in bovine alveolar macrophages infected with virulent and attenuated isogenic strains of Mycobacterium bovis.

Infection with Mycobacterium bovis is a significant human and animal health problem in many parts of the world. The first stage of pulmonary tuberculosis occurs after inhalation of the bacilli into an alveolus where they are ingested by resident macrophages. DNA microarray analysis was used to detect genes expressed in bovine lung alveolar macrophages infected with two isogenic strains of M. bovis, a virulent strain, ATCC35723 and an attenuated strain, WAg520 derived from ATCC35723. Chemokines, interleukin-8 and monocyte chemotactic protein 1, were more strongly expressed in ATCC35723-infected macrophages compared to WAg520-infected macrophages. Conversely, a group of genes, including fibrinogen-like protein 2 and legumain, were expressed at a higher level in macrophages infected with WAg520 compared to ATCC35723. Quantitative real-time PCR of a selected group of these differentially expressed genes confirmed enhanced levels of IL-8 mRNA in ATCC35723-infected macrophages compared to WAg520-infected macrophages. Microarray analysis of gene expression in macrophages infected with attenuated isogenic strains of M. bovis may identify key genes involved in early and protective immune responses to tuberculosis.

Animals↗

Prolonged toll-like receptor signaling by Mycobacterium tuberculosis and its 19-kilodalton lipoprotein inhibits gamma interferon-induced regulation of selected genes in macrophages.

Infection of macrophages with Mycobacterium tuberculosis or exposure to M. tuberculosis 19-kDa lipoprotein for >16 h inhibits gamma interferon (IFN-gamma)-induced major histocompatibility complex class II (MHC-II) expression by a mechanism involving Toll-like receptors (TLRs). M. tuberculosis was found to inhibit murine macrophage MHC-II antigen (Ag) processing activity induced by IFN-gamma but not by interleukin-4 (IL-4), suggesting inhibition of IFN-gamma-induced gene regulation. We designed an approach to test the ability of M. tuberculosis-infected cells to respond to IFN-gamma. To model chronic infection with M. tuberculosis with accompanying prolonged TLR signaling, macrophages were infected with M. tuberculosis or incubated with M. tuberculosis 19-kDa lipoprotein for 24 h prior to the addition of IFN-gamma. Microarray gene expression studies were then used to determine whether prolonged TLR signaling by M. tuberculosis broadly inhibits IFN-gamma regulation of macrophage gene expression. Of 347 IFN-gamma-induced genes, M. tuberculosis and 19-kDa lipoprotein inhibited induction of 42 and 36%, respectively. Key genes or gene products were also examined by quantitative reverse transcription-PCR and flow cytometry, confirming and extending the results obtained by microarray studies. M. tuberculosis inhibited IFN-gamma induction of genes involved in MHC-II Ag processing, Ag presentation, and recruitment of T cells. These effects were largely dependent on myeloid differentiation factor 88, implying a role for TLRs. Thus, prolonged TLR signaling by M. tuberculosis inhibits certain macrophage responses to IFN-gamma, particularly those related to MHC-II Ag presentation. This inhibition may promote M. tuberculosis evasion of T-cell responses and persistence of infection in tuberculosis.

Animals↗

Gene expression profiling of monocyte-derived macrophages following infection with Mycobacterium avium subspecies avium and Mycobacterium avium subspecies paratuberculosis.

Mycobacterium avium subspecies paratuberculosis (MAP) and Mycobacterium avium subspecies avium (MAA) represent two closely related intracellular bacteria with vastly different associated pathologies. MAA can cause severe respiratory infections in immune compromised humans but is nonpathogenic in ruminants and is more readily controlled by the bovine immune system than MAP. MAP causes a fatal wasting syndrome in ruminants, typified by granulomatous enteritis localized in the small intestine. MAP has also been cited as a potential cause of human Crohn's disease. We used a bovine immune-specific microarray (BOTL-5) to compare the response of mature bovine monocyte-derived macrophages (MDM cells) to MAP and MAA. Statistical analysis of microarray data revealed 21 genes not appreciably expressed in resting MDM cells that were activated following infection with either MAA or MAP. Further analysis revealed 144 genes differentially expressed in MDM cells following infection with MAA and 99 genes differentially expressed following infection with MAP. Of these genes, 37 were affected by both types of mycobacteria, with three being affected in opposite directions. Over 41% of the differentially expressed genes in MAA and MAP infected MDM cells were members of, regulated by, or regulators of the MAPK pathways. Expression of selected genes was validated by quantitative real-time reverse transcriptase PCR and in several key genes (i.e., IL-2 receptor, tissue inhibitor of matrix metalloproteinases-1, and Fas-ligand) MAA was found to be a stronger activating factor than MAP. These gene expression patterns were correlated with prolonged activation of p38 MAPK and ERK1/2 by MAA, relative to MAP.

Animals↗

Discovery and validation of a prognostic SPP1/PLAU signature in HPV-negative oropharyngeal squamous cell carcinoma.

BACKGROUND: This study aimed to identify and validate robust prognostic biomarkers for oropharyngeal squamous cell carcinoma (OPSCC), with a specific focus on the high-risk HPV-negative subtype. METHODS: Integrated bioinformatics analysis was performed on transcriptomic data from four GEO datasets (n&#x2009;=&#x2009;418 samples). Differentially expressed genes (DEGs) were identified, and a protein-protein interaction (PPI) network was constructed for the most dysregulated genes. Key modules were analyzed via survival analysis and multivariate Cox regression. The top candidate genes were validated at the protein level using immunohistochemistry (IHC) in an independent cohort of 304 OPSCC patients. RESULTS: A 33-gene module related to extracellular matrix organization showed significant prognostic association. It stratified patients into high- and low-risk groups with markedly different overall survival (HR&#x2009;=&#x2009;2.71, p&#x2009;<&#x2009;0.001). From this module, SPP1 and PLAU were identified as independent prognostic factors through multi-step screening. Both genes were significantly overexpressed in tumors (approximately 20-fold and 10-fold, respectively, p&#x2009;<&#x2009;0.001), with high expression strongly correlated with advanced tumor stage (p&#x2009;<&#x2009;0.01) and, notably, the HPV-negative subtype (p&#x2009;<&#x2009;0.001). In survival analysis, high expression of either SPP1 or PLAU was associated with poorer overall survival (SPP1: p&#x2009;<&#x2009;0.001; PLAU: p&#x2009;<&#x2009;0.001) and progression-free survival (p&#x2009;<&#x2009;0.001). IHC validation confirmed high protein expression in 69.7% (SPP1) and 54.8% (PLAU) of cancer tissues. A prognostic nomogram integrating the SPP1/PLAU signature with clinical variables was constructed with strong predictive accuracy (C-index&#x2009;=&#x2009;0.75). CONCLUSION: The SPP1/PLAU dual-gene signature is a robust and independent prognostic biomarker for OPSCC, with particular clinical utility for stratifying high-risk HPV-negative patients.

Humans↗

Genomic mapping of diabetic kidney disease biomarkers and identification of potential inhibitors through virtual screening.

BACKGROUND: Diabetic kidney disease (DKD) is a common and serious complication of diabetes mellitus, marked by a multifactorial pathogenesis and the absence of sensitive diagnostic biomarkers. Identifying novel molecular targets and therapeutic options is essential to improve early diagnosis and treatment outcomes. METHODS: To uncover potential biomarkers and therapeutic candidates, we performed an integrated genomic analysis using microarray and RNA-seq datasets from the Gene Expression Omnibus (GEO) and Sequence Read Archive (SRA) databases. Differentially expressed genes (DEGs) were identified and subjected to protein-protein interaction (PPI) network analysis. Key genes were further explored through virtual screening of an FDA-approved compound library using molecular docking techniques. Drug-likeness was assessed via Lipinski's rule of five. RESULTS: A total of 40 DEGs were identified, among which ISCU (downregulated; involved in iron-sulfur cluster biogenesis) and AP1S2 (upregulated; associated with vesicular trafficking) emerged as potential biomarkers. PPI analysis revealed their involvement in critical DKD-related pathways, such as extracellular matrix remodeling and oxidative stress. Virtual screening identified six FDA-approved compounds with high binding affinity (&#x2264;-7.96 kcal/mol) to ISCU, notably ZINC000001576020, all of which complied with Lipinski's rule. CONCLUSIONS: This in-silico study nominates ISCU and AP1S2 as candidate diagnostic biomarkers for DKD and identifies computationally prioritized inhibitors targeting ISCU. These findings require experimental validation but provide a molecular framework for precision diagnosis and therapeutic development. These findings offer new molecular insights that could inform precision diagnosis and personalized treatment strategies for diabetic kidney disease.

Diabetic Nephropathies↗

Isolation and characterization of a sheep cysteine-rich cuticle keratin pseudogene.

The cysteine-rich keratin proteins of the hair cuticle are derived from a multigene family that has been highly conserved during mammalian evolution. We have recently characterized one cuticle keratin gene isolated from a sheep lambda library, and Southern blot analysis of that clone suggested the presence of a second related gene. In the present paper sequencing of the second gene has now indicated that it is a pseudogene, a finding supported by a lack of expression in vivo. The pseudogene appears to have arisen by gene duplication, possibly from the adjacent functional gene. Key mutations seem to have occurred in the promoter and processing signals of this gene to render it non-functional and two in-frame termination codons are present in the coding region. A possible recombination point between sequences encoding glycine-rich repeats was identified that could have lead to the creation of the in-frame termination codons.

Amino Acid Sequence↗

[On possible role of chaotic behavior of the gene regulation system in aging].

1. The facts of biology of aging say that the modification of activity of few key genes may lead to the significant increase of life span. 2. The experiments with computational models of gene regulation show that these models are characterized by metastable behavior typical for the chaotic systems. 3. The force of mortality in Gompertz equation grows exponentially in time. It allows to hypothesize that at least at the level of gene regulation aging can be a chaotic process (here implied that chaos is a kind of the complex systems dynamics controlled by strictly determined rules). This approach allows to describe aging from the view point of the information theory--as the forgetting of the right functioning of the organism (i.e. forgetting the state of health) caused by fluctuations (weak nonspecific influencies on the system). Average rate of such forgetting (described by parameter, named Lyapunov exponent) could be identified with the exponent of mortality rate in Gompertz equation. And the parameter inverse to Lyapunov's exponent (Lyapunov time), that describes the time of the initial (healthy) state forgetting, well corresponds to the time of the puberty beginning (i.e. the minimal time for the healthy state to be kept) for human beings, mice, and fruit flies (organisms whose parameters of aging are most perfectly known).

Aging↗

[Gene therapy for the treatment of patients with brain gliomas].

The prognosis of patients with brain gliomas remains poor despite the use of advanced surgical techniques, radio- and chemotherapy. In this respect, gene engineering techniques altering the glioma genome in order to regulate the function of key genes involved in cancerogenesis seem to be promising. The premise for applying a gene therapy in patients with brain gliomas is described, together with basic strategies and results of hitherto performed experimental and clinical studies, mostly with the use of virus vectors. The rapid progress in molecular techniques may enable to overcome methodological problems related to the introduction of the therapeutic gene into the target cell, and thus to improve so far unsatisfactory results of glioma gene therapy. The important role of a neurosurgeon in the process of precise gene vector application to the tumour area should not be underestimated.

Apoptosis Regulatory Proteins↗

Identification and genetic mapping of a novel gene involved in pollen development in arabidopsis.

With an aim of the genetic dissection of anther and pollen development, we identified an Arabidopsis mutant line named zy1511 by ethyl-methane sulphonate (EMS) mutagenesis. Genetic analysis indicated that the mutant phenotype was controlled by a single recessive nuclear gene zy1511. Cytological studies of anther at various developmental stages indicated that the mutant anther tapetum did not start degenerating after microspores released from the tetrads. Part of the mutant anther tapetum still existed at late stages of anther development, indicating that mutant tapetum degenerated later than that of the wild-type. So the mutant microspores could not develop into normal pollen grains in the anther. For the further genetic analysis and the map-based cloning of gene zy1511, we have mapped it to a region of 134 kb between molecular markers F25P12 and T8L23 on chromosome 1 using a map-based cloning strategy. As no male sterile genes have been reported in this region, we believe that zy1511 is an undiscovered key gene involved in pollen development.

Arabidopsis↗

Gefitinib-related gene signature in bladder cancer cells identified by a cDNA microarray.

BACKGROUND: The aim of this study was to identify key genes linked to the molecular action of gefitinib, a promising anticancer agent on human bladder cancer cell lines. MATERIALS AND METHODS: cDNA microarrays were used to profile feature genes in 5637 and T24 cells before and after treatment with gefitinib. PCR-based direct sequencing and Western blot analysis were performed to examine the mutation status and protein levels of EGFR in the cell lines. RESULTS: Gefitinib significantly inhibited the proliferation of 5637 cells, while showing little inhibitory effect on T24 cells. Theses effects were independent of the mutation status and protein levels of EGFR. cDNA microarray analysis identified 15 feature genes classified as a cell cycle, apoptotic pathway and transcription. Notably, levels of expression of the cell invasion-related genes, YY1 and E-cadherin, were increased in 5637 cells sensitive to gefitinib. CONCLUSION: Unique genes involved in the action of gefitinib were identified. Particularly, the upregulation of YY1 and E-cadherin may account for the efficacy of gefitinib in bladder cancer.

Antineoplastic Agents↗

Diversity and evolution of CYCLOIDEA-like TCP genes in relation to flower development in Papaveraceae.

Monosymmetry evolved several times independently during flower evolution. In snapdragon (Antirrhinum majus), a key gene for monosymmetry is CYCLOIDEA (CYC), which belongs to the class II TCP gene family encoding transcriptional activators. We address the questions of the evolutionary history of this gene family and of possible recruitment of genes homologous to CYC in floral development and symmetry in the Papaveraceae. Two to three members of the class II TCP family were found in each species analyzed, two of which were CYC-like genes, on the basis of the presence of both the TCP and R conserved domains. The duplication that gave rise to these two paralogous lineages (named PAPACYL1 and PAPACYL2) probably predates the divergence of the two main clades within the Papaveraceae. Phylogenetic relationships among angiosperm class II TCP genes indicated that (1) PAPACYL genes were closest to Arabidopsis (Arabidopsis thaliana) AtTCP18, and a duplication at the base of the core eudicot would have given rise to two supplementary CYC-like lineages; and (2) at least three class II TCP genes were present in the ancestor of monocots and eudicots. Semiquantitative reverse transcription-polymerase chain reaction and in situ hybridization approaches in three species with different floral symmetry indicated that both PAPACYL paralogs were expressed during floral development. A pattern common to all three species was observed at organ junctions in inflorescences and flowers. Expression in the outer petals was specifically observed in the two species with nonactinomorphic flowers. Hypotheses concerning the ancestral pattern of expression and function of CYC-like genes and their possible role in floral development of Papaveraceae species leading to bisymmetric buds are discussed.

DNA-Binding Proteins↗

The biochemistry of peroxisomal beta-oxidation in the yeast Saccharomyces cerevisiae.

Peroxisomal fatty acid degradation in the yeast Saccharomyces cerevisiae requires an array of beta-oxidation enzyme activities as well as a set of auxiliary activities to provide the beta-oxidation machinery with the proper substrates. The corresponding classical and auxiliary enzymes of beta-oxidation have been completely characterized, many at the structural level with the identification of catalytic residues. Import of fatty acids from the growth medium involves passive diffusion in combination with an active, protein-mediated component that includes acyl-CoA ligases, illustrating the intimate linkage between fatty acid import and activation. The main factors involved in protein import into peroxisomes are also known, but only one peroxisomal metabolite transporter has been characterized in detail, Ant1p, which exchanges intraperoxisomal AMP with cytosolic ATP. The other known transporter is Pxa1p-Pxa2p, which bears similarity to the human adrenoleukodystrophy protein ALDP. The major players in the regulation of fatty acid-induced gene expression are Pip2p and Oaf1p, which unite to form a transcription factor that binds to oleate response elements in the promoter regions of genes encoding peroxisomal proteins. Adr1p, a transcription factor, binding upstream activating sequence 1, also regulates key genes involved in beta-oxidation. The development of new, postgenomic-era tools allows for the characterization of the entire transcriptome involved in beta-oxidation and will facilitate the identification of novel proteins as well as the characterization of protein families involved in this process.

Enzymes↗

Polymorphisms of estrogen-biosynthesis genes CYP17 and CYP19 may influence age at menarche: a genetic association study in Caucasian females.

Variation in age at menarche (AAM) is known to be substantially influenced by genetic factors, but the true causal genes remain largely unidentified. Because the increased amplitude of estrogen exposure of tissues initiates the onset of menarche, the genes involved in estrogen biosynthesis are natural candidate genes underlying AAM. Our study aimed to identify whether the CYP17 and CYP19, the two key genes involved in the biosynthesis of estrogen, are associated with AAM variation in 1048 females from 354 Caucasian nuclear families. We genotyped 38 SNPs and established the linkage disequilibrium blocks and haplotype structures that covered the full transcript length of those two genes. Family-based and population-based statistical analyses were used to test for associations with all of the single SNPs and haplotypes. Both methods consistently detected significant associations for five SNPs of CYP19 with AAM. Haplotype analyses corroborated our single-SNP results by showing that the haplotypes in block 1 were highly significant to AAM in population-based analyses. However, we could not find any association of CYP17 with AAM. Our study is the first to suggest the important effect of CYP19 on AAM variation in Caucasian females. It will be valuable to replicate and confirm these findings in other independent studies, aiming at eventually finding the hidden genetic mechanisms underlying the variation in AAM.

Adolescent↗

Quantitative changes in gene expression in fetal rat testes following exposure to di(n-butyl) phthalate.

Di(n-butyl) phthalate (DBP) alters male reproductive development by decreasing testicular testosterone (T) production when fetuses are exposed on gestation days (GD) 12-21. Previous studies have shown altered gene expression for enzymes in the T biosynthetic pathway following exposure to DBP. The objectives of this study were to develop a more detailed understanding of the effect of DBP on steroidogenesis, using a robust study design with increased numbers of dams and fetuses, compared with previous studies, and to explore messenger RNA (mRNA) expression for other critical genes involved in androgen biosynthesis and signaling. Additionally, immunohistochemical localization of protein expression for several key genes was performed to further confirm mRNA changes. Fetal Leydig cell lipid levels were also examined histochemically, using oil red O. Six to seven pregnant Crl:CD(SD)BR rats per group were gavaged with corn oil or DBP at 500 mg/kg/day on GD 12-19. Testicular RNA isolated from three randomly selected GD 19 fetuses per litter was used for real-time RT-PCR for the following genes: scavenger receptor class B-1 (SRB1), steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), P450c17, 17beta-hydroxysteroid dehydrogenase (17beta-HSD), androgen receptor (AR), luteinizing hormone receptor (LHR), follicle-stimulating hormone receptor (FSHR), stem cell factor tyrosine kinase receptor (c-kit), stem cell factor (SCF), proliferating cell nuclear antigen (PCNA), and testosterone-repressed prostate message-2 (TRPM-2). mRNA expression was downregulated for SRB1, StAR, P450scc, 3beta-HSD, P450c17, and c-kit following DBP exposure, and TRPM-2 was upregulated. 17beta-HSD, AR, LHR, FSHR, and PCNA were not significantly changed. Immunohistochemical staining for c-kit was seen in fetal Leydig cells, which has not been previously reported. Downregulation of most of the genes in the T biosynthetic pathway confirms and extends previous findings. Diminished Leydig cell lipid content and alteration of cholesterol transport genes also support altered cholesterol metabolism and transport as a potential mechanism for decreased T synthesis following exposure to DBP.

Administration, Oral↗

Floral patterning in Lotus japonicus.

Floral patterning in Papilionoideae plants, such as pea (Pisum sativum) and Medicago truncatula, is unique in terms of floral organ number, arrangement, and initiation timing as compared to other well-studied eudicots. To investigate the molecular mechanisms involved in the floral patterning in legumes, we have analyzed two mutants, proliferating floral meristem and proliferating floral organ-2 (pfo-2), obtained by ethyl methanesulfonate mutagenesis of Lotus japonicus. These two mutants showed similar phenotypes, with indeterminate floral structures and altered floral organ identities. We have demonstrated that loss of function of LjLFY and LjUFO/Pfo is likely to be responsible for these mutant phenotypes, respectively. To dissect the regulatory network controlling the floral patterning, we cloned homologs of the ABC function genes, which control floral organ identity in Arabidopsis (Arabidopsis thaliana). We found that some of the B and C function genes were duplicated. RNA in situ hybridization showed that the C function genes were expressed transiently in the carpel, continuously in stamens, and showed complementarity with the A function genes in the heterogeneous whorl. In proliferating floral meristem and pfo-2 mutants, all B function genes were down-regulated and the expression patterns of the A and C function genes were drastically altered. We conclude that LjLFY and LjUFO/Pfo are required for the activation of B function genes and function together in the recruitment and determination of petals and stamens. Our findings suggest that gene duplication, change in expression pattern, gain or loss of functional domains, and alteration of key gene functions all contribute to the divergence of floral patterning in L. japonicus.

Amino Acid Sequence↗