Is optimal gene order impossible?

Poyatos, Juan F.; Hurst, Laurence D.

doi:10.1016/j.tig.2006.06.003

Cited by 29 publications

(32 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The upstream configuration, together with the dynamic nature of the genome, may be a mechanism for constantly tinkering with stabilizing effects or fine-tuning the balance between stability and evolvability (26).…”

Section: Discussionmentioning

confidence: 99%

Gene clustering pattern, promoter architecture, and gene expression stability in eukaryotic genomes

Woo

2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

A balance between gene expression stability and evolvability is essential for the long-term maintenance of a living system. In this paper, we studied whether the genetic and epigenetic properties of the promoter affect gene expression variability. We hypothesized that upstream distance and orientation (head-to-head or head-to-tail) are important for the promoter architecture and gene expression variability. We found that in budding yeast genes with a short upstream distance tend to have low gene expression variability, and their promoter is flanked by strongly positioned nucleosomes and tends to have low nucleosome occupancy. These observations suggest that in vivo positioning of the flanking nucleosomes facilitates stable nucleosome depletion at the core promoter region and enhances gene expression stability. Head-to-head genes have, on average, lower gene expression variability, greater nucleosome depletion at the core promoter region, and more strongly positioned nucleosomes that flank the core promoter than do head-to-tail genes. These observations hold for diverse eukaryotes. In complex organisms such as mammals, only a small fraction of head-to-tail genes have retained a short upstream distance, probably because the promoter may not be flanked by a strongly positioned nucleosome on the upstream side.

show abstract

Section: Discussionmentioning

confidence: 99%

Gene clustering pattern, promoter architecture, and gene expression stability in eukaryotic genomes

Woo

2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Genes and their protein products can interact in a variety of ways: Proteins physically interact, regulate gene expression, modify the activity of other proteins, or catalyze sequential metabolic reactions. Genes encoding functionally related proteins tend to be located close together in the genomes of human (Caron et al 2001; Lee and Sonnhammer 2003;Fukuoka et al 2004;Singer et al 2005;Sémon and Duret 2006;Makino and McLysaght 2008;Michalak 2008;Al-Shahrour et al 2010), yeast (Cohen et al 2000;Pal and Hurst 2003;Poyatos and Hurst 2006), mouse (Li et al 2005;Singer et al 2005), fly (Spellman and Rubin 2002;Mezey et al 2008;Weber and Hurst 2011), worm (Kamath et al 2003), and zebrafish (Ng et al 2009). Significant clustering of functionally related genes in the genome (hereafter termed "functional clustering") has been identified using protein-protein interactions (Poyatos and Hurst 2006;Makino and McLysaght 2009), KEGG pathways (Lee and Sonnhammer 2003), Gene Ontology terms (Al-Shahrour et al 2010), and phenotypes exhibited from gene knockdowns (Kamath et al 2003).…”

mentioning

confidence: 99%

“…Genes encoding functionally related proteins tend to be located close together in the genomes of human (Caron et al 2001; Lee and Sonnhammer 2003;Fukuoka et al 2004;Singer et al 2005;Sémon and Duret 2006;Makino and McLysaght 2008;Michalak 2008;Al-Shahrour et al 2010), yeast (Cohen et al 2000;Pal and Hurst 2003;Poyatos and Hurst 2006), mouse (Li et al 2005;Singer et al 2005), fly (Spellman and Rubin 2002;Mezey et al 2008;Weber and Hurst 2011), worm (Kamath et al 2003), and zebrafish (Ng et al 2009). Significant clustering of functionally related genes in the genome (hereafter termed "functional clustering") has been identified using protein-protein interactions (Poyatos and Hurst 2006;Makino and McLysaght 2009), KEGG pathways (Lee and Sonnhammer 2003), Gene Ontology terms (Al-Shahrour et al 2010), and phenotypes exhibited from gene knockdowns (Kamath et al 2003). Clusters of broadly expressed housekeeping genes (Lercher et al 2002;Singer et al 2005;Michalak 2008;Weber and Hurst 2011), and clusters of coexpressed or tissue-specific genes (Cohen et al 2000;Caron et al 2001;Fukuoka et al 2004;Li et al 2005;Mezey et al 2008;Ng et al 2009;Weber and Hurst 2011) have previously been reported in humans and other eukaryotes.…”

mentioning

confidence: 99%

The clustering of functionally related genes contributes to CNV-mediated disease

et al. 2015

View full text Add to dashboard Cite

Clusters of functionally related genes can be disrupted by a single copy number variant (CNV). We demonstrate that the simultaneous disruption of multiple functionally related genes is a frequent and significant characteristic of de novo CNVs in patients with developmental disorders (P = 1 × 10−3). Using three different functional networks, we identified unexpectedly large numbers of functionally related genes within de novo CNVs from two large independent cohorts of individuals with developmental disorders. The presence of multiple functionally related genes was a significant predictor of a CNV's pathogenicity when compared to CNVs from apparently healthy individuals and a better predictor than the presence of known disease or haploinsufficient genes for larger CNVs. The functionally related genes found in the de novo CNVs belonged to 70% of all clusters of functionally related genes found across the genome. De novo CNVs were more likely to affect functional clusters and affect them to a greater extent than benign CNVs (P = 6 × 10−4). Furthermore, such clusters of functionally related genes are phenotypically informative: Different patients possessing CNVs that affect the same cluster of functionally related genes exhibit more similar phenotypes than expected (P < 0.05). The spanning of multiple functionally similar genes by single CNVs contributes substantially to how these variants exert their pathogenic effects.

show abstract

“…Examples of this would be clusters of co-expressed genes (Boutanaev et al 2002;Lercher et al 2002;Roy et al 2002), clusters of genes that are progressively expressed temporally and/or spatially (Kmita et al 2002;Mahajan and Weissman 2006), and clusters of genes that fall into similar functional classes according to the Gene Ontology or other criteria (Williams and Bowles 2004;Petkov et al 2005). The formation of clusters would occur through tandem duplication events (Zhang and Nei 1996;Aguileta et al 2006) and via chromosomal rearrangements juxtaposing interacting genes (Wong and Wolfe 2005;Poyatos and Hurst 2006). Natural selection would prevent these optimized gene organizations from changing, since change would have a consequential detrimental fitness effect.…”

mentioning

confidence: 99%

“…The promiscuous interaction of long-range enhancers with promoters of neighboring genes could also play a role (Spitz and Duboule 2008). Nevertheless, examples of coordinated co-expression have been reported (Kalmykova et al 2005;Poyatos and Hurst 2006).…”

mentioning

confidence: 99%

Fragile regions and not functional constraints predominate in shaping gene organization in the genus Drosophila

Grotthuss¹,

Ashburner²,

Ranz³

2010

Genome Res.

135

View full text Add to dashboard Cite

During evolution, gene repatterning across eukaryotic genomes is not uniform. Some genomic regions exhibit a gene organization conserved phylogenetically, while others are recurrently involved in chromosomal rearrangement, resulting in breakpoint reuse. Both gene order conservation and breakpoint reuse can result from the existence of functional constraints on where chromosomal breakpoints occur or from the existence of regions that are susceptible to breakage. The balance between these two mechanisms is still poorly understood. Drosophila species have very dynamic genomes and, therefore, can be very informative. We compared the gene organization of the main five chromosomal elements (Muller's elements A-E) of nine Drosophila species. Under a parsimonious evolutionary scenario, we estimate that 6116 breakpoints differentiate the gene orders of the species and that breakpoint reuse is associated with~80% of the orthologous landmarks. The comparison of the observed patterns of change in gene organization with those predicted under different simulated modes of evolution shows that fragile regions alone can explain the observed key patterns of Muller's element A (X chromosome) more often than for any other Muller's element. High levels of fragility plus constraints operating oñ 15% of the genome are sufficient to explain the observed patterns of change and conservation across species. The orthologous landmarks more likely to be under constraint exhibit both a remarkable internal functional heterogeneity and a lack of common functional themes with the exception of the presence of highly conserved noncoding elements. Fragile regions rather than functional constraints have been the main determinant of the evolution of the Drosophila chromosomes.

show abstract

Is optimal gene order impossible?

Cited by 29 publications

References 31 publications

Gene clustering pattern, promoter architecture, and gene expression stability in eukaryotic genomes

Gene clustering pattern, promoter architecture, and gene expression stability in eukaryotic genomes

The clustering of functionally related genes contributes to CNV-mediated disease

Fragile regions and not functional constraints predominate in shaping gene organization in the genus Drosophila

Contact Info

Product

Resources

About