A unification of mosaic structures in the human genome

Lercher, Martin J.; Urrutia, Araxi O.; Pavlı́ček, Adam; Hurst, Laurence D.

doi:10.1093/hmg/ddg251

Cited by 120 publications

(95 citation statements)

References 29 publications

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“…This idea is supported by the finding that genes that are similarly expressed are found in clusters (e.g. genes that are co-expressed [5][6][7] and/or broadly expressed [8,9] and/or highly expressed [10,11]). Second, genome proximity might evolve to reduce the recombination rate between specific genes [12,13].…”

Section: Introductionmentioning

confidence: 94%

Is optimal gene order impossible?

Poyatos

Hurst

2006

Trends in Genetics

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Section: Introductionmentioning

confidence: 94%

Is optimal gene order impossible?

Poyatos

Hurst

2006

Trends in Genetics

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“…In particular, we examine the hypothesis that transcriptional activity provides a possible mechanistic basis for both clustering phenomena (Hurst and Eyre-Walker 2000;Williams and Hurst 2002;Hardison et al 2003). A priori, a coupling with transcriptional activity is an attractive hypothesis, as genes with comparable expression profile cluster (Caron et al 2001;Lercher et al 2003;Versteeg et al 2003) and expression parameters are related to substitution rates (Duret and Mouchiroud 2000). We show here that transcriptional activity appears not to be an important variable underpinning local similarity of rates of evolution.…”

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confidence: 89%

Genomic Regionality in Rates of Evolution Is Not Explained by Clustering of Genes of Comparable Expression Profile

Lercher¹,

Chamary²,

Hurst³

2004

Genome Res.

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In mammalian genomes, linked genes show similar rates of evolution, both at fourfold degenerate synonymous sites (K 4 ) and at nonsynonymous sites (K A ). Although it has been suggested that the local similarity in the synonymous substitution rate is an artifact caused by the inclusion of disparately evolving gene pairs, we demonstrate here that this is not the case: after removal of disparately evolving genes, both (1) linked genes and (2) introns from the same gene have more similar silent substitution rates than expected by chance. What causes the local similarity in both synonymous and nonsynonymous substitution rates? One class of hypotheses argues that both may be related to the observed clustering of genes of comparable expression profile. We investigate these hypotheses using substitution rates from both human-mouse and mouse-rat comparisons, and employing three different methods to assay expression parameters. Although we confirm a negative correlation of expression breadth with both K 4 and K A , we find no evidence that clustering of similarly expressed genes explains the clustering of genes of comparable substitution rates. If gene expression is not responsible, what about other causes? At least in the human-mouse comparison, the local similarity in K A can be explained by the covariation of K A and K 4 . As regards K 4 , our results appear consistent with the notion that local similarity is due to processes associated with meiotic recombination.

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“…Housekeeping genes also typically have small introns (Eisenberg and Levanon, 2003) that lack repetitive sequences (Han et al, 2004). Housekeeping genes have been found to cluster together on the genome to some degree (Lercher et al, 2002), and to preferentially localize to GC-rich fractions of genomic DNA known as isochores on cesium sulfate gradients (Lercher et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Repetitive sequence environment distinguishes housekeeping genes

Eller¹,

Regelson²,

Merriman³

et al. 2007

Gene

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Housekeeping genes are expressed across a wide variety of tissues. Since repetitive sequences have been reported to influence the expression of individual genes, we employed a novel approach to determine whether housekeeping genes can be distinguished from tissue-specific genes their repetitive sequence context. We show that Alu elements are more highly concentrated around housekeeping genes while various longer (>400-bp) repetitive sequences ("repeats"), including Long Interspersed Nuclear Element 1 (LINE-1) elements, are excluded from these regions. We further show that isochore membership does not distinguish housekeeping genes from tissue-specific genes and that repetitive sequence environment distinguishes housekeeping genes from tissue-specific genes in every isochore. The distinct repetitive sequence environment, in combination with other previously published sequence properties of housekeeping genes, were used to develop a method of predicting housekeeping genes on the basis of DNA sequence alone. Using expression across tissue types as a measure of success, we demonstrate that repetitive sequence environment is by far the most important sequence feature identified to date for distinguishing housekeeping genes.

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A unification of mosaic structures in the human genome

Cited by 120 publications

References 29 publications

Is optimal gene order impossible?

Is optimal gene order impossible?

Genomic Regionality in Rates of Evolution Is Not Explained by Clustering of Genes of Comparable Expression Profile

Repetitive sequence environment distinguishes housekeeping genes

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