Ancient Noncoding Elements Conserved in the Human Genome

Venkatesh, Byrappa; Kirkness, Ewen F.; Loh, Yong-Hwee Eddie; Halpern, Aaron L.; Lee, Alison; Johnson, Justin; Dandona, Nidhi; Viswanathan, Lakshmi; Tay, Alice; Venter, J. Craig; Strausberg, Robert L.; Brenner, Sydney

doi:10.1126/science.1130708

Cited by 104 publications

(98 citation statements)

References 7 publications

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“…(3) In addition to sequence conservation, the distances and orientations between LCNS and neighboring coding sequences (genes) are also conserved among multiple species, i.e., the syntenic relationship is conserved. These characteristics of LCNS are consistent with previous observations of CNS (Bejerano et al 2004;de la Calle-Mustienes et al 2005;Dermitzakis et al 2002;Margulies et al 2003;Sandelin et al 2004;Shin et al 2005;Thomas et al 2003;Venkatesh et al 2006;Woolfe et al 2005). We have extracted the LCNS as a very small fraction of the CNS using extremely stringent conditions.…”

Section: Discussionsupporting

confidence: 79%

“…For instance, 2262 CNS (conserved nongenic; length C100 bp and identity C70%) were found by comparing human chromosome 21 and the syntenic mouse region (Dermitzakis et al 2002). Nearly 5000 CNS have been found in comparisons between human and fish (Sandelin et al 2004;Shin et al 2005;Venkatesh et al 2006;Woolfe et al 2005). In addition, Bejerano et al (2004) have identified 481 ultraconserved elements (UCE) of more than 200 bp with 100% identity among the human, mouse, and rat genomes.…”

Section: Introductionmentioning

confidence: 99%

“…However, there is little information about the functional roles of these conserved noncoding sequences (CNS), which, surprisingly, are often much more highly conserved than nucleotide sequences encoding well-conserved proteins. Comparisons of genomic sequences among various vertebrate species have revealed many CNS, which are known by various names (Ahituv et al 2005;Bejerano et al 2004;Dermitzakis et al 2002;Margulies et al 2003;Persampieri et al 2008;Prabhakar et al 2006;Sandelin et al 2004;Shin et al 2005;Siepel et al 2005; Thomas et al 2003;Venkatesh et al 2006;Visel et al 2008;Woolfe et al 2005). For instance, 2262 CNS (conserved nongenic; length C100 bp and identity C70%) were found by comparing human chromosome 21 and the syntenic mouse region (Dermitzakis et al 2002).…”

Section: Introductionmentioning

confidence: 99%

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Identification and characterization of new long conserved noncoding sequences in vertebrates

et al. 2008

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Comparative sequence analyses have identified highly conserved genomic DNA sequences, including noncoding sequences, between humans and other species. By performing whole-genome comparisons of human and mouse, we have identified 611 conserved noncoding sequences longer than 500 bp, with more than 95% identity between the species. These long conserved noncoding sequences (LCNS) include 473 new sequences that do not overlap with previously reported ultraconserved elements (UCE), which are defined as aligned sequences longer than 200 bp with 100% identity in human, mouse, and rat. The LCNS were distributed throughout the genome except for the Y chromosome and often occurred in clusters within regions with a low density of coding genes. Many of the LCNS were also highly conserved in other mammals, chickens, frogs, and fish; however, we were unable to find orthologous sequences in the genomes of invertebrate species. In order to examine whether these conserved sequences are functionally important or merely mutational cold spots, we directly measured the frequencies of ENUinduced germline mutations in the LCNS of the mouse. By screening about 40.7 Mb, we found 35 mutations, including mutations at nucleotides that were conserved between human and fish. The mutation frequencies were equivalent to those found in other genomic regions, including coding sequences and introns, suggesting that the LCNS are not mutational cold spots at all. Taken together, these results Electronic supplementary materialThe online version of this article

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification and characterization of new long conserved noncoding sequences in vertebrates

et al. 2008

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“…For example, teleosts have experienced a higher rate of gene-linkage disruption and chromosomal rearrangements (Kasahara et al, 2007;Semon and Wolfe, 2007a;Venkatesh et al, 2007;Hufton et al, 2008), faster evolution of protein-coding sequences (Robinson-Rechavi and Laudet, 2001;Jaillon et al, 2004;Brunet et al, 2006) and conserved noncoding elements (CNEs) (Chiu et al, 2002;Venkatesh et al, 2006) compared to cartilaginous fishes and mammals, and have a large number of teleost lineage-specific genes (Yang et al, 2013). The potential implications of these processes in the diversification and rapid speciation of teleost fishes have been extensively discussed (Ravi and Venkatesh, 2008;Yang et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Genome-wide identification and characterization of teleost-specific microRNAs within zebrafish

Yang

Irwin

2015

Gene

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“…Recently, the elephant shark (Callorhinchus milii), a chimera, has been proposed as a model cartilaginous fish genome because of its compact genome size (910 Mb). (13,15) Survey sequencing of the elephant shark genome, sampling approximately 75% of the genome, has identified over 15,000 genes in this cartilaginous fish. (13) We used the elephant shark genome to investigate whether it possesses any members of the Pth gene family.…”

Section: J Jbmrmentioning

confidence: 99%

Parathyroid hormone gene family in a cartilaginous fish, the elephant shark (Callorhinchus milii)

Liu¹,

Ibrahim²,

Tay³

et al. 2010

Journal of Bone and Mineral Research

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The development of bone was a major step in the evolution of vertebrates. A bony skeleton provided structural support and a calcium reservoir essential for the movement from an aquatic to a terrestrial environment. Cartilaginous fishes are the oldest living group of jawed vertebrates. In this study we have identified three members of the parathyroid hormone (Pth) gene family in a cartilaginous fish, the elephant shark (Callorhinchus milii). The three genes include two Pth genes, designated as Pth1 and Pth2, and a Pthrp gene. Phylogenetic analysis suggested that elephant shark Pth2 is an ancient gene whose orthologue is lost in bony vertebrates. The Pth1 and Pth2 genes have the same structure as the Pth gene in bony vertebrates, whereas the structure of the Pthrp gene is more complex in tetrapods compared with elephant shark. The three elephant shark genes showed distinct patterns of expression, with Pth2 being expressed only in the brain and spleen. This contrasts with localization of the corresponding proteins, which showed considerable overlap in their distribution. There were conserved sites of localization for Pthrp between elephant shark and mammals, including tissues such as kidney, skin, skeletal and cardiac muscle, pancreas, and cartilage. The elephant shark Pth1(1-34) and Pthrp(1-34) peptides were able to stimulate cAMP accumulation in mammalian UMR106.01 cells. However, Pth2(1-34) peptide did not show such PTH-like biologic activity. The presence of Pth and Pthrp genes in the elephant shark indicates that these genes played fundamental roles before their recruitment to bone development in bony jawed vertebrates. ß

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Ancient Noncoding Elements Conserved in the Human Genome

Cited by 104 publications

References 7 publications

Identification and characterization of new long conserved noncoding sequences in vertebrates

Identification and characterization of new long conserved noncoding sequences in vertebrates

Genome-wide identification and characterization of teleost-specific microRNAs within zebrafish

Parathyroid hormone gene family in a cartilaginous fish, the elephant shark (Callorhinchus milii)

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