Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Signature”

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 541 records · Page 30Linked to original sources
PubMed2004

YODA: selecting signature oligonucleotides.

MOTIVATION: Selecting oligonucleotide probes for use in microarray design, and other applications requiring signature sequences, involves identifying sequences which will bind strongly to their intended target, while binding only weakly (or preferably, not at all) to non-target sequences which may be present in the hybridization reaction. While many tools to assist in selection of such sequences exist, all the ones we examined lack important oligo design and software features. RESULTS: YODA is an application for assisting biological researchers in selecting signature sequences. It incorporates a custom sequence similarity search to find potential cross-hybridizing non-target sequences. For this task, most oligo design tools rely on BLAST, which is ill suited for it due to an unacceptable risk of false negatives. YODA supports multiple probe design goals including single-genome, multiple-genome, pathogen-host and species/strain-identification. A graphical interface is provided as well as a command-line interface, both of which support many user-controlled parameters. YODA is easy to install and use and runs on Windows, Mac OS X and Linux platforms. AVAILABILITY: Freely available (LGLP) along with source code and additional documentation at http://pathport.vbi.vt.edu/YODA CONTACT: enordber@vbi.vt.edu.

Algorithms↗
PubMed2004

The bioenergetic signature of lung adenocarcinomas is a molecular marker of cancer diagnosis and prognosis.

The aim of this study was to investigate the mitochondrial bioenergetic signature of lung adenocarcinomas as a prognostic marker of cancer progression. For this purpose, a series of 90 lung adenocarcinomas and 10 uninvolved lung samples were examined for quantitative differences in protein expression using two-dimensional polyacrylamide gel electrophoresis. The beta subunit of the mitochondrial H(+)-ATP synthase (beta-F1-ATPase) and heat shock protein 60 (Hsp 60), and the glycolytic glyceraldehyde-3-phosphate dehydrogenase (GAPDH), used to define the bioenergetic cellular (BEC) index, were identified using mass spectrometry and specific antibodies. Correlations of the expression level of the protein markers and of the BEC index were established with the clinicopathological information of the tumors and the follow-up data of the patients. The expression of beta-F1-ATPase is significantly reduced in lung adenocarcinomas in the absence of significant changes in the expression of Hsp 60 and of a major GAPDH isoform. Cross-validation analysis using the beta-F1-ATPase/Hsp 60 ratio and GAPDH expression as predictor variables revealed a classification sensitivity of 97.3%. The beta-F1-ATPase/Hsp 60 ratio is significantly higher in well differentiated and bronchioloalveolar tumors than in moderate or poorly differentiated and in bronchial-derived tumors. The BEC index of T1 tumors was significantly higher than that of T2 tumors. Likewise, stage IA tumors had a higher BEC index than stage IB tumors. Kaplan-Meier survival analysis using the BEC index as predictor of survival revealed that within tumors of the same size or stage I or with no lymph node metastasis (N0) the patients bearing 'low' BEC index tumors had a significant worse prognosis. We conclude that the bioenergetic signature of lung adenocarcinomas is altered, further providing a relevant marker for the diagnosis and classification of lung adenocarcinomas, and for the prognosis of lung cancer patients.

Adenocarcinoma↗
PubMed1998

Alteration of N-terminal phosphoesterase signature motifs inactivates Saccharomyces cerevisiae Mre11.

Saccharomyces cerevisiae Mre11, Rad50, and Xrs2 function in a protein complex that is important for nonhomologous recombination. Null mutants of MRE11, RAD50, and XRS2 are characterized by ionizing radiation sensitivity and mitotic interhomologue hyperrecombination. We mutagenized the four highly conserved phosphoesterase signature motifs of Mre11 to create mre11-11, mre11-2, mre11-3, and mre11-4 and assessed the functional consequences of these mutant alleles with respect to mitotic interhomologue recombination, chromosome loss, ionizing radiation sensitivity, double-strand break repair, and protein interaction. We found that mre11 mutants that behaved as the null were sensitive to ionizing radiation and deficient in double-strand break repair. We also observed that these null mutants exhibited a hyperrecombination phenotype in mitotic cells, consistent with previous reports, but did not exhibit an increased frequency of chromosome loss. Differential ionizing radiation sensitivities among the hypomorphic mre11 alleles correlated with the trends observed in the other phenotypes examined. Two-hybrid interaction testing showed that all but one of the mre11 mutations disrupted the Mre11-Rad50 interaction. Mutagenesis of the phosphoesterase signatures in Mre11 thus demonstrated the importance of these conserved motifs for recombinational DNA repair.

Amino Acid Sequence↗
PubMed2000

Imaging spatial and cellular characteristics of low temperature calcium signature after cold acclimation in Arabidopsis.

Cooling-induced 'calcium signatures' were imaged in aequorin-expressing Arabidopsis plants after cold acclimation or growth at ambient temperature. In all tissues, signatures were altered after acclimation. Characterization of the components generating this response indicates that cold acclimation increases cold-induced vacuolar Ca(2+) release, but does not affect the influx of extracellular calcium.

Adaptation, Physiological↗
PubMed2001

Quantification of insect nitrogen utilization by the venus fly trap Dionaea muscipula catching prey with highly variable isotope signatures.

Dionaea is a highly specialized carnivorous plant species with a unique mechanism for insect capture. The leaf is converted into an osmotically driven trap that closes when an insect triggers sensory trichomes. This study investigates the significance of insect capture for growth of Dionaea at different successional stages after a fire, under conditions where the prey is highly variable in its isotope signature. The contribution of insect-derived nitrogen (N) was estimated using the natural abundance of 15N. In contrast to previous 15N studies on carnivorous plants, the problem emerges that delta15N values of prey insects ranged between -4.47 per thousand (grasshoppers) and +7.21 per thousand (ants), a range that exceeds the delta15N values of non carnivorous reference plants (-4.2 per thousand) and soils (+3 per thousand). Thus, the isotope-mixing model used by Shearer and Kohl to estimate the amount of insect-derived N is not applicable. In a novel approach, the relationships of delta15N values of different organs with delta15N of trapping leaves were used to estimate N partitioning within the plant. It is estimated that soon after fire approximately 75% of the nitrogen is obtained from insects, regardless of plant size or developmental stage. The estimates are verified by calculating the average isotope signatures of insects from an isotope mass balance and comparing this with the average measured delta15N values of insects. It appears that for Dionaea to survive and reach the flowering stage, seedlings must first reach the 6th-leaf rosette stage, in which trap surface area nearly doubles and facilitates the capture of large insects. Large amounts of nitrogen thus made available to plants may facilitate an enhanced growth rate and the progressive production of additional large traps. Dionaea reaches a maximum abundance after fire when growth of the competing vegetation is suppressed. About 10 years after fire, when grasses and shrubs recover, Dionaea becomes overtopped by other species. This would not only reduce carbon assimilation but also the probability of catching larger prey. The amount of insect-derived nitrogen decreases to 46%, and Dionaea becomes increasingly dependent on N-supply from the soil. Competition for both light and N may cause the near disappearance of Dionaea in older stages of the fire succession.

Animals↗
PubMed2003

UV-induced blue-green and far-red fluorescence along wheat leaves: a potential signature of leaf ageing.

Under UV-excitation, leaves emit red (RF) and far-red (FRF) fluorescence from chlorophyll and blue-green fluorescence (BGF) from hydroxycinnamic acids. In this study, the aim was to develop a fluorescence signature of wheat leaf ageing after the emergence of the lamina. FRF and BGF were examined in the first three leaves of 2-week-old wheat plants. It was investigated how FRF and BGF vary as leaf and tissue aged by spectroscopic measurements, time-resolved BGF analysis and microscopic imaging of the leaf surface. It was found that FRF decreased with leaf and tissue ageing because of an accumulation of UV-absorbers in the epidermis. BGF also decreased, but without changes either in the shape of excitation and emission spectra or in the fluorescence lifetime. So, BGF emanated from the leaf surface, without changes in fluorophore composition during leaf ageing. The shape of the BGF spectrum indicates that ferulic acid bound to the cell wall is the main blue-green fluorophore. The effects of pH and solvents on BGF from intact leaves and ferulic acid in solution were similar, confirming the hydroxycinnamic acid origin of BGF. UV-fluorescence microscopic imaging of the surface of intact leaves showed that different epidermis cell types and sclerenchyma bands emitted BGF. The decreasing gradient of BGF from the base to the apex of the lamina could be related to the decrease in the surface of the fluorescent sclerenchyma bands. The significance of FRF and BGF as potential signatures of wheat lamina growth are discussed.

Apoptosis↗
PubMed2004

Nucleotide variability at the acetyl coenzyme A carboxylase gene and the signature of herbicide selection in the grass weed Alopecurus myosuroides (Huds.).

Acetyl coenzyme A carboxylase (ACCase) is the target of highly effective herbicides. We investigated the nucleotide variability of the ACCase gene in a sample of 18 black-grass (Alopecurus myosuroides [Huds.]) populations to search for the signature of herbicide selection. Sequencing 3,396 bp encompassing ACCase herbicide-binding domain in 86 individuals revealed 92 polymorphisms, which formed 72 haplotypes. The ratio of nonsynonymous versus synonymous substitutions was very low, in agreement with ACCase being a vital metabolic enzyme. Within black grass, most nonsynonymous substitutions were related to resistance to ACCase-inhibiting herbicides. Differentiation between populations was strong, in contrast to expectations for an allogamous, annual plant. Significant H tests revealed recent hitchhiking events within populations. These results were consistent with recent and local positive selection. We propose that, although they have only been used since at most 15 black-grass generations, ACCase-inhibiting herbicides have exerted a positive selection targeting resistant haplotypes that has been strong enough to have a marked effect upon ACCase nucleotide diversity. A minimum-spanning network of nonrecombinant haplotypes revealed multiple, independent apparitions of resistance-associated mutations. This study provides the first evidence for the signature of ongoing, recent, pesticide selection upon variation at the gene encoding the targeted enzyme in natural plant populations.

Acetyl-CoA Carboxylase↗
PubMed1996

Transcriptional repression by Rev-erbA alpha is dependent on the signature motif and helix 5 in the ligand binding domain: silencing does not involve an interaction with N-CoR.

Rev-erbA alpha is an orphan nuclear receptor that functions as a dominant transcriptional repressor. Tissue culture and in situ hybridisation studies indicated that Rev-erbA alpha plays an important role in mammalian differentiation and development. Previous studies have localised the silencing domain of Rev-erbA alpha to the D/E region of the orphan receptor. This study utilised the GAL4 hybrid system to demonstrate that efficient repression is mediated by 34 amino acids (aa) between aa 455 and 488 in the E region of the receptor. This domain contains the ligand binding domain (LBD)-signature motif [(F/W)AKxxxxFxxLxxxDQxxLL] and a region that, according to the recently published crystal structures of steroid receptors, would be predicted to form helix 5 of the canonical LBD structure. Fine deletions and site-specific mutagenesis indicated that both the LBD signature motif and helix 5 were necessary for efficient silencing. Utilising mammalian two hybrid technology, we have also demonstrated that Rev-erbA alpha does not associate with the interaction domain (aa 2218-2451) of the nuclear receptor corepressor, N-CoR, that is known to interact with the thyroid hormone and retinoic acid receptors. This suggested that transcriptional repression by Rev-erbA alpha is not mediated through an interaction with N-CoR. In conclusion, we have identified and characterised the minimal domain of Rev-erbA alpha, that mediates transcriptional repression by this orphan receptor.

Amino Acid Sequence↗
PubMed2005

GENSTYLE: exploration and analysis of DNA sequences with genomic signature.

GENSTYLE (http://Genstyle.imed.jussieu.fr) is a workspace designed for the characterization and classification of nucleotide sequences. Based on the genomic signature paradigm, GENSTYLE focuses on oligonucleotide frequencies in DNA sequences. Users can select sequences of interest in the GENSTYLE companion database, where the whole set of GenBank sequences is grouped per species, or upload their own sequences to work with. Tools for the exploration and analysis of signatures allow (i) identification of the origin of DNA segments (detection of rare species or species for which technical problems prevent fast characterization, such as micro-organisms with slow growth), (ii) analysis of the homogeneity of a genome and isolation of areas with novel functionality (horizontal transfers for example)--and (iii) molecular phylogeny and taxonomy.

Databases, Nucleic Acid↗
PubMed2002

Human hypoxic signal transduction through a signature motif in hepatocyte nuclear factor 4.

We identified a human hypoxic signal transduction pathway acting through a signature motif in the carboxyl terminal of hepatocyte nuclear factor 4 (HNF-4), by functional comparison of the transcriptional and protein-protein interaction activities of the wild type and mutants. It was previously shown that HNF-4 functions as a tissue-specific and hypoxia-activated transcription factor for the erythropoietin (Epo) gene. Human HNF-4 (465 amino acid residues) has DNA-binding, ligand-binding, and transactivation domains. The deletion mutant without the carboxyl terminal transactivation domain (amino acids 369-465) has been shown to be a dominant-negative mutant that repressed Epo transcriptional activity in hypoxia. Further characterization of the hypoxia-responsive domain by site-directed mutagenesis indicated that a TKQE motif of the carboxyl terminal (amino acids 460-463) in HNF-4 was essential for hypoxia-inducible Epo gene expression. We also found, by means of immunoprecipitation and a mammalian two-hybrid system, direct interactions between HNF-4 and hypoxia-inducible factor 1 (HIF-1), a heterodimer composed of alpha and beta subunits. HNF-4 was observed to interact with HIF-1alpha and HIF-1beta (arylhydrocarbon receptor nuclear translocator, ARNT) during hypoxia. In addition, the TKQE motif of HNF-4 was essential for protein-protein interactions with HIF-1alpha and ARNT. These results indicate that the human hypoxic signal of HIF-1 is transduced through interactions with the signature TKQE motif of the carboxyl terminal of HNF-4, resulting in Epo gene expression as a response to hypoxia.

Amino Acid Motifs↗
PubMed2006

Signatures of differentially regulated interferon gene expression and vasculotrophism in the peripheral blood cells of systemic sclerosis patients.

OBJECTIVE: To obtain a global view of the immunological alterations occurring in early systemic sclerosis (SSc) by transcriptional profiling of peripheral blood cells (PBCs). METHODS: Oligonucleotide microarrays were used to compare PBC gene expression profiles in 18 SSc cases (<2 yr duration) and 18 controls matched for race, gender and ethnicity. SSc cases had no prior or current exposure to cytotoxic drugs. PAXgene tubes were used to stabilize RNA during phlebotomy. Changes in gene expression were independently validated by real-time polymerase chain reaction. RESULTS: SSc PBCs demonstrated differential expression of 18 interferon-inducible genes. Six of these genes were identical to the interferon signature genes in lupus peripheral blood mononuclear cells. Notably, SSc PBCs also had increased expression of allograft inflammatory factor (AIF1) and several selectins and integrins involved in cellular adhesion to the endothelium. Global analysis of 284 known biological pathways revealed that 13 were differentially regulated in SSc PBCs, including two pathways (IL2RB and GATA3) that lead to T(H)2 polarization. CONCLUSIONS: Transcriptional profiling reliably discriminates between PBCs from SSc and normal donors despite the fact that they represent a heterogeneous cell population. Multiple biological pathways were differentially regulated in SSc PBCs, but a common thread across these pathways was alterations in protein tyrosine kinase 2beta and mitogen-activated protein kinase signalling. Although the SSc PBC gene expression profile demonstrated some parallels with the lupus interferon gene signature, there was also increased expression of transcripts encoding proteins that target PBCs to the endothelium, which might be relevant to the vasculopathy of SSc.

Adult↗
PubMed2005

Signal signature and transcriptome changes of Arabidopsis during pathogen and insect attack.

Plant defenses against pathogens and insects are regulated differentially by cross-communicating signaling pathways in which salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) play key roles. To understand how plants integrate pathogen- and insect-induced signals into specific defense responses, we monitored the dynamics of SA, JA, and ET signaling in Arabidopsis after attack by a set of microbial pathogens and herbivorous insects with different modes of attack. Arabidopsis plants were exposed to a pathogenic leaf bacterium (Pseudomonas syringae pv. tomato), a pathogenic leaf fungus (Alternaria brassicicola), tissue-chewing caterpillars (Pieris rapae), cell-content-feeding thrips (Frankliniella occidentalis), or phloem-feeding aphids (Myzus persicae). Monitoring the signal signature in each plant-attacker combination showed that the kinetics of SA, JA, and ET production varies greatly in both quantity and timing. Analysis of global gene expression profiles demonstrated that the signal signature characteristic of each Arabidopsis-attacker combination is orchestrated into a surprisingly complex set of transcriptional alterations in which, in all cases, stress-related genes are overrepresented. Comparison of the transcript profiles revealed that consistent changes induced by pathogens and insects with very different modes of attack can show considerable overlap. Of all consistent changes induced by A. brassicicola, Pieris rapae, and E occidentalis, more than 50% also were induced consistently by P. syringae. Notably, although these four attackers all stimulated JA biosynthesis, the majority of the changes in JA-responsive gene expression were attacker specific. All together, our study shows that SA, JA, and ET play a primary role in the orchestration of the plant's defense response, but other regulatory mechanisms, such as pathway cross-talk or additional attacker-induced signals, eventually shape the highly complex attacker-specific defense response.

Alternaria↗
PubMed2003

The ownership signature in mouse scent marks is involatile.

Male house mice advertise their territory ownership through urinary scent marks and use individual-specific patterns of major urinary proteins (MUPs) to discriminate between their own scent and that of other males. It is not clear whether recognition occurs through discrimination of the non-volatile proteins or protein-ligand complexes (direct model), or by the detection of volatile ligands that are released from MUPs (indirect model). To examine the mechanism underlying individual scent mark signatures, we compared investigatory and countermarking responses of male laboratory mice presented with male scent marks from a strain with a different MUP pattern, when they could contact the scent or when contact was prevented by a porous nitrocellulose sheet to which proteins bind. Mice investigated scent marks from other males whether these were covered or not, and biochemical analysis confirmed that the porous cover did not prevent the release of volatiles from scent marks. Having gained information through investigation, mice increased their own scent marking only if they had direct contact with another male's urine, failing to do this when contact was prevented. Individual signatures in scent marks thus appear to be carried by non-volatile proteins or by non-volatile protein-ligand complexes, rather than by volatiles emanating from the scent.

Animal Communication↗
PubMed1992

Identification of a third genomic group of Borrelia burgdorferi through signature nucleotide analysis and 16S rRNA sequence determination.

As part of a continuing effort to assess genetic variation among isolates of Borrelia burgdorferi we have determined the 16S rRNA signature nucleotide makeup of two tick isolates from the USSR. Signature nucleotides were identified via reverse transcriptase primer extension sequencing of select regions of the 16S rRNA molecule. In addition, the near complete 16S rRNA sequence of one of the isolates, R-IP3, was determined and utilized in a phylogenetic assessment. The sequence was aligned with the 16S rRNA sequences of other B. burgdorferi isolates as well as with other Borrelia species. Distance matrix analyses were performed and a phylogenetic tree was constructed. These analyses demonstrate that these isolates belong to a third previously unidentified genomic group of B. burgdorferi.

Base Sequence↗
PubMed2006

Molecular signatures in protein sequences that are characteristics of the phylum Aquificae.

Species of the phylum Aquificae are of great interest due to their strict extreme thermophilic growth characteristics. Presently, there is no known molecular characteristic which is unique to this group of bacteria. This work describes six conserved inserts and deletions (indels or signature sequences) in four widely distributed proteins that are distinctive features of species from the phylum Aquificae. These include three signatures consisting of a 2 aa insert, a 5-6 aa insert and a 6 aa deletion in DNA polymerase I (PolA), a 6-7 aa insert in glucose-inhibited protein A (GidA), a 52 aa insert in the RNA polymerase beta'-subunit (RpoC) and a 4 aa insert in elongation factor Tu (EF-Tu). Fragments of these genes were amplified in most cases from Hydrogenobacter hydrogenophilus, Hydrogenothermus marinus and Thermocrinis ruber and combined with available sequence data from 'Aquifex aeolicus' and Sulfurihydrogenibium azorense. The presence of the PolA, GidA and RpoC indels in all of the species sequenced provides evidence that they are probably distinctive characteristics of the entire phylum. The indel in EF-Tu, which is shared by Aquifex species and Hydrogenobacter but not Hydrogenothermus and Sulfurihydrogenibium, may provide a molecular marker for the family Aquificaceae. We have also identified a 51 aa insert in SecA preprotein translocase that is commonly shared by various species of the Aquificae as well as two Thermotoga species (Thermotoga maritima and Thermotoga neapolitana) which may be due to lateral gene transfer between these groups. In phylogenetic trees based on a concatenated dataset of fragments from eight different proteins as well as 16S rRNA, the observed branching pattern of these species was very similar and it was consistent with the relationships inferred from various indels. The identified indels provide a novel means for distinguishing species of the Aquificae from all other bacteria in molecular terms and may prove useful for functional studies aimed at understanding the unique biochemical and physiological characteristics of the Aquificae.

Adenosine Triphosphatases↗
PubMed2003

Application of a novel multi-screening signature-tagged mutagenesis assay for identification of Klebsiella pneumoniae genes essential in colonization and infection.

Klebsiella pneumoniae is a common cause of urinary tract infections (UTIs) and pneumonia, especially in immunocompromised individuals. Epidemiological studies have revealed that K. pneumoniae infections are frequently preceded by gastrointestinal colonization and the gastrointestinal tract is believed to be the most important reservoir for transmission of the bacteria. To identify genes involved in the ability of K. pneumoniae to colonize the intestine and infect the urinary tract, a novel multi-screening signature-tagged mutagenesis (MS-STM) assay was implemented. In the MS-STM assay, PCR-amplified tags present in the inoculum as well as recovered pools from each infection model are simultaneously subjected to hybridization using each specific tag as a probe. Therefore, screenings of a mutant library in more than one infection model is significantly eased compared to the traditional signature-tagged mutagenesis methodology. From a total of 1,440 K. pneumoniae transposon mutants screened, 13 mutants were identified as attenuated in intestinal colonization as well as the UTI model. In addition, six mutants attenuated only in the UTI model were identified. Transposon insertion sites in attenuated mutants were, among others, in genes encoding well-known K. pneumoniae virulence factors such as lipopolysaccharide and capsule, as well as in genes of unknown function.

Animals↗
PubMed2000

MHC class II pseudogene and genomic signature of a 32-kb cosmid in the house finch (Carpodacus mexicanus).

Large-scale sequencing studies in vertebrates have thus far focused primarily on the genomes of a few model organisms. Birds are of interest to genomics because of their much smaller and highly streamlined genomes compared to mammals. However, large-scale genetic work has been confined almost exclusively to the chicken; we know little about general aspects of genomes in nongame birds. This study examines the organization of a genomic region containing an Mhc class II B gene in a representative of another important lineage of the avian tree, the songbirds (Passeriformes). We used a shotgun sequencing approach to determine the sequence of a 32-kb cosmid insert containing a strongly hybridizing Mhc fragment from house finches (Carpodacus mexicanus). There were a total of three genes found on the cosmid clone, about the gene density expected for the mammalian Mhc: a class II Mhc beta-chain gene (Came-DAB1), a serine-threonine kinase, and a zinc finger motif. Frameshift mutations in both the second and third exons of Came-DAB1 and the unalignability of the gene after the third exon suggest that it is a nonfunctional pseudogene. In addition, the identifiable introns of Came-DAB1 are more than twice as large as those of chickens. Nucleotide diversity in the peptide-binding region of Came-DAB1 (Pi = 0.03) was much lower than polymorphic chicken and other functional Mhc genes but higher than the expected diversity for a neutral locus in birds, perhaps because of hitchhiking on a selected Mhc locus close by. The serine-threonine kinase gene is likely functional, whereas the zinc finger motif is likely nonfunctional. A paucity of long simple-sequence repeats and retroelements is consistent with emerging rules of chicken genomics, and a pictorial analysis of the "genomic signature" of this sequence, the first of its kind for birds, bears strong similarity to mammalian signatures, suggesting common higher-order structures in these homeothermic genomes. The house finch sequence is among a very few of its kind from nonmodel vertebrates and provides insight into the evolution of the avian Mhc and of avian genomes generally.

Animals↗
PubMed2003

The signature of selection mediated by expression on human genes.

As the efficacy of natural selection is expected to be a function of population size, in humans it is usually presumed that selection is a weak force and hence that gene characteristics are mostly determined by stochastic forces. In contrast, in species with large population sizes, selection is expected to be a much more effective force. Evidence for this has come from examining how genic parameters vary with expression level, which appears to determine many of a gene's features, such as codon bias, amino acid composition, and size. However, not until now has it been possible to examine whether human genes show the signature of selection mediated by expression level. Here, then, to investigate this issue, we gathered expression data for >10,000 human genes from public data sets obtained by different technologies (SAGE and high-density oligonucleotide chip arrays) and compared them with gene parameters. We find that, even after controlling for regional effects, highly expressed genes code for smaller proteins, have less intronic DNA, and higher codon and amino acid biases. We conclude that, contrary to the usual supposition, human genes show signatures consistent with selection mediated by expression level.

Chromosome Mapping↗