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PubMed2026

Microrna Expression in Aurelia aurita Metamorphosis.

INTRODUCTION: In animal taxa and jellyfish, the same genome encodes for the different phenotypes that characterize life stages that follow each other during ontogeny. This situation underscores the existence of profound regulation of genomic information at the epigenetic level. MicroRNAs are fundamental epigenetic regulators. The aim of this study is to evaluate the role of microRNA regulation during jellyfish metamorphosis and to explore the existence of evolutionarily conserved microRNAs. METHODS: Specimens belonging to the 4-metamorphosis stages of A. aurita (polyps, ephyra, young, and adult jellyfish) were bred and collected. The expression of 2,549 miRNAs for each stage was tested using microarray technology. The comparison of microRNA expression for each phase was performed using line plot analysis and Principal Component Analysis of variance (PCA), while the identification of microRNA clusters was performed via volcano plot analysis. RESULTS: A remarkable number of A. aurita miRNAs specifically hybridize with a human miRNA library. Each metamorphosis stage is characterized by a different level of expression of miRNAs: 1) Polyp vs. Ephyra stage: 128 upregulated, 2 downregulated; 2) Ephyra vs. Young stage: 2 upregulated, 135 downregulated; 3) Young vs. Adult stage: 69 upregulated, 6 downregulated. Specific functions inferred from known activities of corresponding miRNAs in higher animals (PubMed database) appear to be coherent with the correlated experimental model. DISCUSSION: Present results reveal that microRNAs with human homologs undergo specific expression changes throughout Aurelia aurita metamorphosis. This observation reinforces the hypothesis of a shared evolutionary origin of certain miRNA families between Cnidaria and Bilateria. The dynamic and stage-specific regulation pattern observed suggests that miRNAs play a key role in orchestrating the complex transitions involved in jellyfish development. These findings point to a broader conservation of epigenetic mechanisms, such as miRNA-mediated gene silencing, which may have emerged early in metazoan evolution and contributed to the regulation of cell differentiation and phenotype modulation. CONCLUSION: The present study highlights the importance of Aurelia aurita as a model for investigating miRNA-driven epigenetic regulation in non-bilaterian animals. The identification of human-homologous miRNAs provides novel insights into the evolutionary stability of the epigenetic machinery and suggests conserved regulatory functions across distant taxa. Although limited by the use of a human-based microarray platform, the data presented here lay a solid foundation for future studies employing sequencing and functional assays to further explore the role of miRNAs in cnidarian development and evolution.

Animals↗

PubMed2002

Relationship between p53 codon 72 polymorphism and susceptibility to sunburn and skin cancer.

Upregulation of p53 protein induces either growth arrest or apoptosis in response to cellular injury This is signaled from a highly conserved p53 domain between codons 64 and 92, where a functional polymorphism results in either a proline (p53-72P) or an arginine (p53-72R) at codon 72. Preliminary studies suggest that p53-72R may be a risk factor for cervical cancer and, consistent with this, preferential mutation and retention of the p53-72R allele has also been demonstrated in other cancers of squamous cell origin. Here we examine the relationship between allelic forms of p53 and nonmelanoma skin cancer, by determining the correlation with susceptibility to sunburn, which is a known risk factor, and then by p53 sequence analysis of a large series of tumors. We found a significant positive association between p53-72R and susceptibility to sunburn, as assessed by skin phototype and minimal erythemal dose following solar-simulated radiation (p = 0.0001 for trend). We also found a significant association between p53-72R homozygosity and nonmelanoma skin cancer in renal transplant recipients (basal cell carcinoma, p < 0.01; squamous cell carcinoma, p < 0.05) but not in immunocompetent patients compared with skin type matched controls. p53 sequence data revealed mutations in 30 of 70 (42.9%) nonmelanoma skin cancers, 28 (93%) of which were in the p53-72R allele. Loss of heterozygosity occurred more frequently in p53-72RP than in p53-72RR tumors (p = 0.0001) with preferential loss of p53-72P in heterozygotes (p = 0.016), irrespective of the mutant status of the concomitant allele. Together these data infer functional differences between polymorphic forms of p53 that are likely to be relevant to skin carcinogenesis.

Adolescent↗

PubMed1998

Histopathologic analysis of failed vascularized fibular grafts in femoral head osteonecrosis.

Salient histopathological features in 13 failed free vascularized fibular autografts implanted for osteonecrosis of the femoral head are documented. Of particular clinical and/or biomechanical relevance are 1-2-mm-thick seams of viable lamellar bone bonded circumferentially to anatomically intact but necrotic graft cortices, which appear to preclude their revascularization and remodeling. Surrounding the grafts are 3-6-mm-thick rings of reactive bone, fused in many sites (average approximately 54%) to the osseous seams. They consist of a layer of sclerotic cortical-like bone melded with an outer layer of thickened cancellous bone. This remodeled reactive bone, largely the result of drilling, appears to buttress the grafts structurally and by inference, functionally. Operative failures in all but one case are attributed primarily to collapse of the necrotic, fractured superior subtending segment of the graft and of the subchondral plate secondary to size and progression of the osteonecrosis and superimposed osteoarthrosis. Morphological integrity of grafts elsewhere and perifibular reactive sclerotic bone remain unimpaired for up to 5 1/2 years. The salutary features of vascularized autografts would appear to give them a decided advantage over their nonvascularized counterpart.

Adult↗

PubMed1985

Formation of new rod photoreceptor synapses onto differentiated bipolar cells in goldfish retina.

In goldfish new rods are continuously added to the entire retina at a rate that assures stable rod density, while the densities of other neurons decrease. The b1 bipolar, known to contact every rod within its dendritic domain, was used to determine the fate of these newly formed rods. Golgi-stained b1 bipolars were sectioned serially at 0.5 micron in the plane of the receptor terminals and reconstructions of their rod and cone contacts were prepared from camera lucida drawings. The newly formed rods are accommodated within the dendritic trees of already-formed b1 bipolars at a rate of about one new rod synapse/bipolar/month. During growth from about 6 months to 5 years of age the number of synapses onto each b1 bipolar increases by 50%. Concomitantly the dendritic tree area increases by about 50%, and the density of rod-b1 synapses remains constant at about one synapse/11 micron 2. Assuming a dendritic coverage factor of 1, the b1 bipolars will contact every retinal rod. The numbers of cones contacted and not contacted do not significantly change. The overall dimensions of b1 bipolars increase with retinal growth and new branches are added to their dendritic trees. These observations show that new rods added to adult goldfish retina form synapses with old bipolars. Some functional inferences are also made.

Animals↗

PubMedDate not supplied

Gene and protein profiling of the response of MA-10 Leydig tumor cells to human chorionic gonadotropin.

Activation of the steroidogenic machinery by peptide hormones involves a number of steps for transmitting signals from the plasma membrane to mitochondria in a spatially and temporally coordinated manner. Although key proteins mediating the hormonal signal have been identified, recent data suggest that the pathway might involve more complex protein-protein and protein-lipid interactions. Genomic and proteomic methods of analysis, namely the Affymetrix Murine Genome U74A v2 GeneChip and the BD PowerBlot Western Array, were used to identify human chorionic gonadotropin (hCG)-induced changes in mRNA and protein of MA-10 Leydig tumor cells that parallel the increase seen in progesterone synthesis. To analyze the massive amount of data that was generated, a comprehensive protein information matrix summarizing the features of each gene or protein, including its known properties, as well as annotations derived by homology-based functional inference, was developed. Of the genes examined by Affymetrix array, approximately 79 were differentially expressed and of gene products examined by PowerBlot, 9 were differentially expressed (above twofold). Changes in the expression of selected transcripts of interest were confirmed using real-time quantitative polymerase chain reaction and immunoblot analyses. Collectively, these results indicate that hormonal regulation of steroidogenesis is a complex phenomenon, involving proteins that participate in various known and novel pathways, which are implicated in transmitting signals from the plasma membrane to mitochondria and nucleus.

Blotting, Western↗

PubMed2005

Morphological variation of the thoracolumbar vertebrae in Macropodidae and its functional relevance.

The present study was designed to investigate how the form of the marsupial thoracolumbar vertebrae varies to cope with the particular demands of diverse loading and locomotor behaviors. The vertebral columns of 10 species of Macropodidae, with various body masses and modes of locomotion, together with two other arboreal marsupials, koala and cuscus, were selected. Seventy-four three-dimensional landmark coordinates were acquired on each of the 10 last presacral vertebrae of the 70 vertebral columns. The interspecific variations of the third lumbar vertebra (L3, which approximates the mean) and the transitional patterns of the thoracolumbar segments were examined using the combined approach of generalized Procrustes analysis (GPA) and principal components analysis (PCA). The results of analyses of an individual vertebra (L3) and of the transitional patterns indicate significant interspecific differences. In the L3 study the first PC shows allometric shape variation, while the second PC seems to relate to adaptation for terrestrial versus arboreal locomotion. When the L3 vertebrae of the common spotted cuscus and koala are included for comparison, the vertebra of the tree kangaroo occupies an intermediate position between the hopping kangaroo and these arboreal marsupials. The L3 vertebrae in the arboreal marsupials possess a distinct dorsoventrally expanded vertebral body, and perpendicularly orientated spinous and transverse processes. The results of the present study suggest that vertebral shape in the kangaroo and wallaroos provides a structural adaptation to hopping through a relatively enlarged loading area and powerful lever system. In contrast, the small-sized bettongs (or rat kangaroos) have a relatively flexible column and elongated levers for the action of back muscles that extend and laterally flex the spine. The complex pattern of vertebral shape transition in the last 10 presacral vertebrae was examined using PCAs that compare between species information about vertebral shape variation along the thoracolumbar column. The results reinforce and emphasize important aspects of the patterns of variation seen in the detailed analysis of the third lumbar vertebra. The results also imply that size, spinal loading pattern, and locomotor behavior exert an influence on shaping the vertebra. Further, the morphological adaptations are consistent within these marsupials and this opens up the possibility that this kind of analysis may be useful in making functional inferences from fossil material.

Animals↗

PubMed1998

Chromosomal locations of three human nuclear genes (RPSM12, TUFM, and AFG3L1) specifying putative components of the mitochondrial gene expression apparatus.

We have mapped the chromosomal locations of three human nuclear genes for putative components of the apparatus of mitochondrial gene expression, using a combination of in situ hybridization and interspecies hybrid mapping. The genes RPMS12 (mitoribosomal protein S12, a conserved protein component of the mitoribosomal accuracy center), TUFM (mitochondrial elongation factor EF-Tu), and AFG3L1 (similar to the yeast genes Afg3 and Rca1 involved in the turnover of mistranslated or misfolded mtDNA-encoded polypeptides) were initially characterized by a combination of database sequence analysis, PCR, cloning, and DNA sequencing. RPMS12 maps to chromosome 19q13.1, close to the previously mapped gene for autosomal dominant hearing loss DFNA4. The TUFM gene is located on chromosome 16p11.2, with a putative pseudogene or variant (TUFML) located very close to the centromere of chromosome 17. AFG3L1 is located on chromosome 16q24, very close to the telomere. By virtue of their inferred functions in mitochondria, these genes should be regarded as candidates of disorders sharing features with mitochondrial disease syndromes, such as sensorineural deafness, diabetes, and retinopathy.

ATPases Associated with Diverse Cellular Activitie↗

PubMed1999

Gleaning non-trivial structural, functional and evolutionary information about proteins by iterative database searches.

Using a number of diverse protein families as test cases, we investigate the ability of the recently developed iterative sequence database search method, PSI-BLAST, to identify subtle relationships between proteins that originally have been deemed detectable only at the level of structure-structure comparison. We show that PSI-BLAST can detect many, though not all, of such relationships, but the success critically depends on the optimal choice of the query sequence used to initiate the search. Generally, there is a correlation between the diversity of the sequences detected in the first pass of database screening and the ability of a given query to detect subtle relationships in subsequent iterations. Accordingly, a thorough analysis of protein superfamilies at the sequence level is necessary in order to maximize the chances of gleaning non-trivial structural and functional inferences, as opposed to a single search, initiated, for example, with the sequence of a protein whose structure is available. This strategy is illustrated by several findings, each of which involves an unexpected structural prediction: (i) a number of previously undetected proteins with the HSP70-actin fold are identified, including a highly conserved and nearly ubiquitous family of metal-dependent proteases (typified by bacterial O-sialoglycoprotease) that represent an adaptation of this fold to a new type of enzymatic activity; (ii) we show that, contrary to the previous conclusions, ATP-dependent and NAD-dependent DNA ligases are confidently predicted to possess the same fold; (iii) the C-terminal domain of 3-phosphoglycerate dehydrogenase, which binds serine and is involved in allosteric regulation of the enzyme activity, is shown to typify a new superfamily of ligand-binding, regulatory domains found primarily in enzymes and regulators of amino acid and purine metabolism; (iv) the immunoglobulin-like DNA-binding domain previously identified in the structures of transcription factors NFkappaB and NFAT is shown to be a member of a distinct superfamily of intracellular and extracellular domains with the immunoglobulin fold; and (v) the Rag-2 subunit of the V-D-J recombinase is shown to contain a kelch-type beta-propeller domain which rules out its evolutionary relationship with bacterial transposases.

Actins↗

PubMed1990

The largest convex patches: a boundary-based method for obtaining object parts.

The importance of boundaries for shape decomposition into component parts has been discussed from different points of view by Koenderink and van Doorn (1982), and by Hoffman and Richards (1984). The former define part boundaries as parabolic contours, whereas the latter propose that part boundaries should be defined by contours of negative minima (or maxima) of principal curvature. In this article, building on aspects of both approaches, we develop a new method for shape decomposition. This method relies exclusively on global properties of the surface which are fully characterized by local surface properties. We propose that a useful parcellation of shapes into parts can be obtained by decomposing the shape boundary into the largest convex surface patches and the smallest nonconvex surface patches. The essential computational steps of this method are the following: (i) build initial parts from the largest locally convex patches, (ii) consider an initial part as a constituent part if it is essentially convex, and (iii) obtain the remaining constituent parts by merging adjacent initial parts generated by the largest locally convex and the smallest nonconvex patches of nearly the same sizes. The method is illustrated on both smooth and continuous shapes. We show that the decomposition of shapes into the largest convex patches aims to maximize the "thingness" in an object, and to minimize its "non-thingness". The method is conducive to a natural parcellation of shapes into constituent parts useful for recognition and for inferring function.

Form Perception↗

PubMed1987

Detection and estimation of neural connectivity based on crosscorrelation analysis.

Crosscorrelation analysis of simultaneously recorded activity of pairs of neurons is a common tool to infer functional neural connectivity. The adequacy of crosscorrelation procedures to detect and estimate neural connectivity has been investigated by means of computer simulations of small networks composed of fairly realistic modelneurons. If the mean interval of neural firings is much larger than the duration of postsynaptic potentials, which will be the case in many central brain areas excitatory connections are easier to detect than inhibitory ones. On the other hand, inhibitory connections are revealed better if the mean firing interval is much smaller than post-synaptic potential duration. In general the effects of external stimuli and the effects of neural connectivity do not add linearly. Furthermore, neurons may exhibit a certain degree of timelock to the stimulus. For these reasons the commonly applied "shift predictor" procedure to separate stimulus and neural effects appears to be of limited value. In case of parallel direct and indirect neural pathways between two neurons crosscorrelation analysis does not estimate the direct connection but instead an effective connectivity, which reflects the combined influences of the parallel pathways.

Animals↗

PubMed2001

Origin, diversity and evolution of NBS-type disease-resistance gene homologues in coffee trees (Coffea L.).

The majority of plant disease-resistance genes (R-genes) isolated so far encode a predicted nucleotide-binding site (NBS) domain. NBS domains related to R-genes show a highly conserved backbone of amino acid motifs, which makes it possible to isolate resistance gene analogues (RGAs) by PCR with degenerate primers. Multiple combinations of primers with low degeneracy, designed from two conserved motifs in the NBS regions of R-genes of various plants, were used on genomic DNA from coffee trees, an important perennial tropical crop. Nine distinct classes of RGAs of the NBS-like type, representing a highly diverse sample, were isolated from Coffea arabica and C. canephora species. The analysis of one coffee RGA family suggested point mutations as the primary source of diversity. With one exception, coffee RGA families appeared to be closely related in sequence to at least one cloned R-gene. In addition, deduced amino acid sequences of coffee RGAs were identified that showed strong sequence similarity to almost all known non-TIR (Toll/Interleukin 1 Receptor)-type R-genes. The high degree of similarity between particular coffee RGAs and R-genes isolated from other angiosperm species, such as Arabidopsis, tomato and rice, indicates an ancestral relationship and the existence of common ancestors. The data obtained from coffee species suggests that the evolution of NBS-encoding sequences involves the gradual accumulation of mutations and slow rates of divergence within distinct R-gene families, rather than being a rapid process. Functional inferences drawn from the suggested pattern of evolution of NBS-type R-genes is also discussed.

Amino Acid Sequence↗

PubMed2005

The active site residue tyrosine 325 influences iron binding and coupling efficiency in human phenylalanine hydroxylase.

Phenylalanine hydroxylase (PAH) is a tetrahydrobiopterin (BH(4))-dependent enzyme that catalyzes the hydroxylation of l-Phe to l-Tyr. The non-heme iron in the enzyme (Fe(III) as isolated) is 6-coordinated to a 2-His-1-carboxylate motif and three water molecules (wat1, wat2 and wat3). Tyr325 is at the second coordination sphere, hydrogen-bonded to water (wat1). We prepared and expressed mutants with Leu, Ala, Ser and Phe at this position. Only Y325L and the conservative mutation Y325F resulted in stable enzymes, but the mutant Y325F has been found to be post-translationally hydroxylated and to revert back to wild-type PAH [S.D. Kinzie, M. Thevis, K. Ngo, J. Whitelegge, J.A. Loo, M.M. Abu-Omar, J. Am. Chem. Soc. 125 (2003) 4710-4711], being inadequate to investigate the early inferred functional role of Tyr325. On the other hand, compared to wild-type PAH, Y325L shows reduced specific activity, decreased coupling efficiency and decreased iron content. The mutant also reveals a very high affinity for l-Phe and BH(4) and does not manifest positive cooperativity for the substrate. All together, our results support that the mutation Y325L causes the removal or increased delocalization of the iron-ligated wat1 and, in turn, a less tight binding of the metal. Tyr325 thus appears to have an important role ensuring stoichiometric binding of iron, correct geometry of the complexes with substrate and cofactor and, consequently, a right coupling efficiency of the PAH reaction. In addition, the residue appears to be important for the correct cooperative regulation by l-Phe.

Base Sequence↗

PubMed2003

How well is enzyme function conserved as a function of pairwise sequence identity?

Enzyme function conservation has been used to derive the threshold of sequence identity necessary to transfer function from a protein of known function to an unknown protein. Using pairwise sequence comparison, several studies suggested that when the sequence identity is above 40%, enzyme function is well conserved. In contrast, Rost argued that because of database bias, the results from such simple pairwise comparisons might be misleading. Thus, by grouping enzyme sequences into families based on sequence similarity and selecting representative sequences for comparison, he showed that enzyme function starts to diverge quickly when the sequence identity is below 70%. Here, we employ a strategy similar to Rost's to reduce the database bias; however, we classify enzyme families based not only on sequence similarity, but also on functional similarity, i.e. sequences in each family must have the same four digits or the same first three digits of the enzyme commission (EC) number. Furthermore, instead of selecting representative sequences for comparison, we calculate the function conservation of each enzyme family and then average the degree of enzyme function conservation across all enzyme families. Our analysis suggests that for functional transferability, 40% sequence identity can still be used as a confident threshold to transfer the first three digits of an EC number; however, to transfer all four digits of an EC number, above 60% sequence identity is needed to have at least 90% accuracy. Moreover, when PSI-BLAST is used, the magnitude of the E-value is found to be weakly correlated with the extent of enzyme function conservation in the third iteration of PSI-BLAST. As a result, functional annotation based on the E-values from PSI-BLAST should be used with caution. We also show that by employing an enzyme family-specific sequence identity threshold above which 100% functional conservation is required, functional inference of unknown sequences can be accurately accomplished. However, this comes at a cost: those true positive sequences below this threshold cannot be uniquely identified.

Animals↗

PubMed2006

A systematic literature review to investigate if we identify those patients who can cope with anterior cruciate ligament deficiency.

Rupture of the anterior cruciate ligament (ACL) results in increased tibiofemoral laxity in the knee, thereby ultimately resulting in knee instability and dysfunction. However, ACL rupture does not automatically infer functional impairment and instability as confirmed by the ACL deficient (ACLD) coper, who can resume pre-morbid activity levels. Alternatively, an authentic ACLD non-coper is unable to return to pre-injury levels of activity due to repeated incidents of giving-way. Little is known as to the contributory factors, which allows copers dynamic stability and render non-copers functionally impaired. This systematic literature review aims to examine the evidence presented by relevant trials in order to identify measurement tools, which could differentiate ACLD copers and non-copers. A literature search found nine trials; four adhered to the inclusion criteria of this review. Consensus was achieved within the studies that laxity measurements and IKDC ratings are incapable of distinguishing the functional status of the ACLD patient. Alternatively, Lysholm, KOS-Sport, KOS-ADL and Global Knee Function Rating Scores were regarded as capable of discriminating between ACLD copers and non-copers. Disagreement existed as to the efficacy of the Quadriceps Index and the single leg hop in categorising the ACLD patient according to function level. It was concluded that no single measurement tool is sufficient in determining the functional status of the ACLD individual. Consequently, a collaboration of tests is recommended, specifically incorporating the KOS-Sport, Global Knee Function Rating, hop tests and Quadriceps Index.

Adaptation, Physiological↗

PubMed2026

Splenic extramedullary hematopoiesis in myelofibrosis is shaped by transcriptomic and epigenetic dysregulation.

Myelofibrosis (MF) is a chronic, progressive myeloproliferative neoplasm characterized by bone marrow fibrosis, ineffective blood cell production, and neoplastic extramedullary hematopoiesis (EMH) occurring primarily within the spleen. To explore the molecular mechanisms underlying splenic EMH, we performed single-cell transcriptional and chromatin profiling of cells from MF spleens that had been surgically removed. We demonstrate significant expansion of hematopoietic stem and progenitor cells, coupled with aberrant differentiation toward the erythroid and megakaryocytic lineages, associated with a significant enrichment of inflammatory pathways with enhanced NF-κB signaling and IFN responses, as well as dysregulation of the inferred function of differentiation-defining transcription factors. Finally, we report a significant remodeling of the immune microenvironment in MF spleens, characterized by emergence of dysfunctional T cell subsets and inflammatory memory B cells, suggesting the concomitant establishment of a pro-inflammatory and immune-tolerant tumor microenvironment within the spleen that influences hematopoietic cell differentiation and impairs tumor immune surveillance.

Primary Myelofibrosis↗

PubMed1998

The nos (nitrous oxide reductase) gene cluster from the soil bacterium Achromobacter cycloclastes: cloning, sequence analysis, and expression.

The nitrous oxide (N2O) reductase (nos) gene cluster from Achromobacter cycloclastes has been cloned and sequenced. Seven protein coding regions corresponding to nosR, nosZ (structural N2O reductase gene), nosD, nosF, nosY, nosL, and nosX are detected, indicating a genetic organization similar to that of Rhizobium meliloti. To aid homology studies, nosR from R. meliloti has also been sequenced. Comparison of the deduced amino acid sequences with corresponding sequences from other organisms has also allowed structural and functional inferences to be made. The heterologous expression of NosD, NosZ (N2O reductase), and NosL is also reported. A model of the CuA site in N2O reductase, based on the crystal structure of this site in bovine heart cytochrome c oxidase, is presented. The model suggests that a His residue of the CuA domain may be a ligand to the catalytic CuZ site. In addition, the origin of the spectroscopically-observed Cys coordination to CuZ is discussed in terms of the sequence alignment of seven N2O reductases.

Alcaligenes↗

PubMed2002

Vertebrate genome sequencing: building a backbone for comparative genomics.

The human genome sequence provides a reference point from which we can compare ourselves with other organisms. Interspecies comparison is a powerful tool for inferring function from genomic sequence and could ultimately lead to the discovery of what makes humans unique. To date, most comparative sequencing has focused on pair-wise comparisons between human and a limited number of other vertebrates, such as mouse. Targeted approaches now exist for mapping and sequencing vertebrate bacterial artificial chromosomes (BACs) from numerous species, allowing rapid and detailed molecular and phylogenetic investigation of multi-megabase loci. Such targeted sequencing is complementary to current whole-genome sequencing projects, and would benefit greatly from the creation of BAC libraries from a diverse range of vertebrates.

Animals↗

PubMed2001

A peptide profile of the Bacillus subtilis genome.

Bacillus subtilis is known to produce an abundance of small polypeptides. Several of these have antimicrobial activity and others are pheromones or extracellular factors that affect internal signal transduction systems. The completion of the B. subtilis genomic nucleotide sequence has revealed 345 small polypeptide open-reading frames (of 85 codons or less), 81% of which are of unknown function. A significant number of these reside in prophage genomes or phage-like elements where they can be organized into large operons. It is likely that many more exist in the genome of B. subtilis but are "hidden" entirely or partially within other reading frames, or possess non-conventional translation start signals and have escaped detection. The discovery of so many small polypeptide orfs (SPORFs) and the likelihood of many more pose a challenging problem for those undertaking the complete functional analysis of genes that constitute prokaryotic genomes. A survey of known and potential peptide-encoding reading frames is presented herein as an attempt to classify those that are found in the B. subtilis genome according to function inferred from homology searches and to conservation among products of other microbial genomes.

Amino Acid Sequence↗