Selection for short introns in highly expressed genes

Castillo-Davis, Cristian I.; Mekhedov, Sergei; Hartl, Daniel L.; Koonin, Eugene V.; Kondrashov, Fyodor A.

doi:10.1038/ng940

Cited by 474 publications

(442 citation statements)

References 29 publications

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“…Previously [8], the high abundance of a certain gene in EST libraries was an indication the gene was highly expressed in the human body. It was pointed out [8], however, that this method is prone to bias due to the inclusion of normalized and tumor libraries and overrepresentation of certain tissues. Our approach overcomes this difficulty and confirms the previous result.…”

Section: Length Analysis Of Hk Genesmentioning

confidence: 99%

“…The more copies of a gene required for the organism, the stronger this pressure should be. The first demonstration of this principle [8] showed that genes with a large number of expressed sequence tags (ESTs) in public libraries (and hence most mRNAs) have a significantly shorter average intron length than those with fewer ESTs.Here, an implication of this principle is used to validate a set of HK genes. The HK genes, which are transcribed in all somatic cells and under all circumstances, are by nature highly expressed, and therefore should be selected to have shorter introns.…”

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Human housekeeping genes are compact

2003

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We identify a set of 575 human genes that are expressed in all conditions tested in a publicly available database of microarray results. Based on this common occurrence, the set is expected to be rich in "housekeeping" genes, showing constitutive expression in all tissues. We compare selected aspects of their genomic structure with a set of background genes. We find that the introns, untranslated regions and coding sequences of the housekeeping genes are shorter, indicating a selection for compactness in these genes. 1The amazing diversity of the human body stems from the different expression patterns of genes in different tissues. Although most genes show constitutive expression in only a subset of tissues, some gene products are required for the maintenance of the basal cellular function and are constitutively found in all human cells. These genes are called housekeeping genes (HK genes) [1]. HK genes can be used to calibrate measurements of gene expression [2].They might also help to define the minimal gene complement needed for a human cell [1].Several attempts have been made recently to define the complete set of HK genes [3,4].Microarrays are often used to identify sets of genes that are expressed either ubiquitously or in specific tissues or conditions. However, the technique is technically demanding and prone to artifacts, so independent evidence is often required to confirm the results. In principle, identifying the set of HK genes using microarray data is straightforward; one need only look for genes that are expressed in all tissues and all experimental conditions.Employing such an approach has so far resulted in two lists of HK genes [3,4]. However, problems in probe design, measurement noise and other artifacts introduce inevitable errors in such lists. Because a northern blot experiment for each gene in each tissue is impractical, an independent test is needed to validate any list of HK genes. Here, we report a validation test that uses a recently discovered property of highly expressed genes.The transcription process is both slow and costly; it takes 50 milliseconds [5,6] and two ATP molecules [7] approximately to transcribe a nucleotide. This might be expected to provide selective pressure to make genes as short as functionally possible. The more copies of a gene required for the organism, the stronger this pressure should be. The first demonstration of this principle [8] showed that genes with a large number of expressed sequence tags (ESTs) in public libraries (and hence most mRNAs) have a significantly shorter average intron length than those with fewer ESTs.Here, an implication of this principle is used to validate a set of HK genes. The HK genes, which are transcribed in all somatic cells and under all circumstances, are by nature highly expressed, and therefore should be selected to have shorter introns. We used a recently published database of microarray experiments [9] to identify a set of HK genes. As a further validation step, we checked the Gene Ontology (GO) annotation of thes...

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Section: Length Analysis Of Hk Genesmentioning

confidence: 99%

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confidence: 99%

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Human housekeeping genes are compact

2003

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“…Surprisingly, while highly expressed genes were found to be shorter in animals and to harbor fewer and shorter introns [30], they appear least compact and relatively largest in plants [33] and C. elegans [29]. Several evolutionary scenarios such as selection for economy and genomic design have been discussed to explain the observed trends [31,34].…”

Section: Multistimuli Response Genes Are Shorter In Arabidopsismentioning

confidence: 99%

“…The correlation between expression level and gene size and associated properties such as number and length of introns has been investigated in several studies [28][29][30][31][32][33][34]. Surprisingly, while highly expressed genes were found to be shorter in animals and to harbor fewer and shorter introns [30], they appear least compact and relatively largest in plants [33] and C. elegans [29].…”

Section: Multistimuli Response Genes Are Shorter In Arabidopsismentioning

confidence: 99%

The regulatory code for transcriptional response diversity and its relation to genome structural properties in Arabidopsis thaliana

Walther¹,

Brunnemann²,

Selbig³

2005

PLoS Genet

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Regulation of gene expression via specific cis-regulatory promoter elements has evolved in cellular organisms as a major adaptive mechanism to respond to environmental change. Assuming a simple model of transcriptional regulation, genes that are differentially expressed in response to a large number of different external stimuli should harbor more distinct regulatory elements in their upstream regions than do genes that only respond to few environmental challenges. We tested this hypothesis in Arabidopsis thaliana using the compendium of gene expression profiling data available in AtGenExpress and known cis-element motifs mapped to upstream gene promoter regions and studied the relation of the observed breadth of differential gene expression response with several fundamental genome architectural properties. We observed highly significant positive correlations between the density of ciselements in upstream regions and the number of conditions in which a gene was differentially regulated. The correlation was most pronounced in regions immediately upstream of the transcription start sites. Multistimuli response genes were observed to be associated with significantly longer upstream intergenic regions, retain more paralogs in the Arabidopsis genome, are shorter, have fewer introns, and are more likely to contain TATA-box motifs in their promoters. In abiotic stress time series data, multistimuli response genes were found to be overrepresented among early-responding genes. Genes involved in the regulation of transcription, stress response, and signaling processes were observed to possess the greatest regulatory capacity. Our results suggest that greater gene expression regulatory complexity appears to be encoded by an increased density of cis-regulatory elements and provide further evidence for an evolutionary adaptation of the regulatory code at the genomic layout level. Larger intergenic spaces preceding multistimuli response genes may have evolved to allow greater regulatory gene expression potential.Citation: Walther D, Brunnemann R, Selbig J (2007) The regulatory code for transcriptional response diversity and its relation to genome structural properties in A. thaliana. PLoS Genet 3(2): e11.

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Chloroplast genomes of two Pueraria DC. species: sequencing, comparative analysis and molecular marker development

Yang

et al. 2021

FEBS Open Bio

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Puerariae lobatae radix (Ge-Gen in Chinese) and Puerariae thomsonii radix (Fen-Ge) are widely used as medicine and health products, particularly in Chinese medicine. Puerarin and daidzein are the primary bioactive compounds in Puerariae radix. These isoflavones have been used to treat cardiovascular and cerebrovascular diseases, hypertension, diabetes, and osteoporosis. The content of puerarin in Ge-Gen is about six times higher than that in Fen-Ge, so its use has a higher pharmacological effect. It is therefore of great importance to effectively distinguish between these two species. However, because their basal plants, P. lobata (Willd.) Ohwi and P. thomsonii Benth., possess an extremely similar appearance, and detecting the level of chemical constituents is just a rough distinction, it is necessary to develop more efficient identification approaches. Here the complete chloroplast genomes of P. lobata and P. thomsonii were deciphered, including sequencing, assembly, comparative analysis, and molecular marker development. The results showed that they are 153,393 and 153,442 bp in length, respectively; both contain 124 annotated genes, including eight encoding rRNA, 29 encoding tRNA, and 87 encoding proteins. Phylogenetic analysis showed that they form a clade, indicating that they originate from the same ancestor. After obtaining 10 intergenic/intronic regions with a genetic distance greater than 0.5 cm, primers were designed to amplify regions of high variability in P. lobata and P. thomsonii. Finally, a 60-bp differential base fragment, located in the intron of rpl16, was developed as a molecular marker to efficiently distinguish between these two species.Puerariae lobatae radix, known as Ge-Gen in Chinese, is a popular traditional Chinese herbal medicine that was first described in the Shennong Herbal Classic. The genus Pueraria DC. belongs to the Fabaceae family and comprises about 20 species worldwide. It is mainly distributed in East Asian countries, among which China is the distribution center, accounting for 11 species. The dried roots of Ge-Gen have been widely used for the treatment of influenza, muscle stiffness, and other sicknesses [1]. Owing to a multi-origin traditional Chinese medicine, there are two Pueraria species: Pueraria lobata (Willd.) Ohwi and Pueraria thomsonii Benth., whose roots were considered the main source of Ge-Gen because of the wide distribution and

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Selection for short introns in highly expressed genes

Cited by 474 publications

References 29 publications

Human housekeeping genes are compact

Human housekeeping genes are compact

The regulatory code for transcriptional response diversity and its relation to genome structural properties in Arabidopsis thaliana

Chloroplast genomes of two Pueraria DC. species: sequencing, comparative analysis and molecular marker development

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