Inferring Nonneutral Evolution from Human-Chimp-Mouse Orthologous Gene Trios

Clark, Andrew G.; Glanowski, Stephen; Nielsen, Rasmus; Thomas, Paul D.; Kejariwal, Anish; Todd, Melissa; Tanenbaum, David M.; Civello, Daniel; Lu, Fu; Murphy, Brian J.; Ferriera, Steve; Wang, Gary; Zheng, Xianqgun; White, Thomas J.; Sninsky, John J.; Adams, Mark D.; Cargill, Michele

doi:10.1126/science.1088821

Cited by 622 publications

(592 citation statements)

References 19 publications

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“…In the comparative genomics community, much attention has focused on two problems in particular: (1) identifying (especially noncoding) sequences that are unusually conserved across species, and thus are likely to be subject to negative selection (e.g., [3][4][5][6]); and (2) identifying protein-coding genes that show unusually high d N /d S ratios, and thus might be subject to positive selection (e.g., [7][8][9][10][11][12]). Methods focused on problem (1) generally have made the assumption (explicitly or implicitly) that selectional pressures are the same across all branches of a phylogeny-i.e., that each candidate sequence is under selection in all species or not under selection in any species.…”

Section: Introductionmentioning

confidence: 99%

New Methods for Detecting Lineage-Specific Selection

Siepel

Pollard

Haussler

2006

Lecture Notes in Computer Science

224

210

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Abstract. So far, most methods for identifying sequences under selection based on comparative sequence data have either assumed selectional pressures are the same across all branches of a phylogeny, or have focused on changes in specific lineages of interest. Here, we introduce a more general method that detects sequences that have either come under selection, or begun to drift, on any lineage. The method is based on a phylogenetic hidden Markov model (phylo-HMM), and does not require element boundaries to be determined a priori, making it particularly useful for identifying noncoding sequences. Insertions and deletions (indels) are incorporated into the phylo-HMM by a simple strategy that uses a separately reconstructed "indel history." To evaluate the statistical significance of predictions, we introduce a novel method for computing P -values based on prior and posterior distributions of the number of substitutions that have occurred in the evolution of predicted elements. We derive efficient dynamic-programming algorithms for obtaining these distributions, given a model of neutral evolution. Our methods have been implemented as computer programs called DLESS (Detection of LinEage-Specific Selection) and phyloP (phylogenetic P -values). We discuss results obtained with these programs on both real and simulated data sets.

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Section: Introductionmentioning

confidence: 99%

New Methods for Detecting Lineage-Specific Selection

Siepel

Pollard

Haussler

2006

Lecture Notes in Computer Science

224

210

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“…COCH has since been shown to be mutated in DFNA9, a dominantly inherited sensorineural deafness and vestibular disorder (Robertson et al, 1998). Examination of UniGene dbEST and NCBI Blast searches suggests that OTOR is an inner ear-specific gene (Beisel et al, 2004) and under human-specific selection (Clark et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Expression studies of osteoglycin/mimecan (OGN) in the cochlea and auditory phenotype of Ogn-deficient mice

et al. 2008

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Genes involved in the hearing process have been identified through both positional cloning efforts following genetic linkage studies of families with heritable deafness and by candidate gene approaches based on known functional properties or inner ear expression. The latter method of gene discovery may employ a tissue-or organ-specific approach. Through characterization of a human fetal cochlear cDNA library, we have identified transcripts that are preferentially and/or highly expressed in the cochlea. High expression in the cochlea may be suggestive of a fundamental role for a transcript in the auditory system. Herein we report the identification and characterization of a transcript from the cochlear cDNA library with abundant cochlear expression and unknown function that was subsequently determined to represent osteoglycin (OGN). Ogn-deficient mice, when analyzed by auditory brainstem response and distortion product otoacoustic emissions, have normal hearing thresholds. Keywords mimecan/osteoglycin; proteoglycan; hearing loss #Correspondence to: Cynthia C. Morton, PhD, Brigham and Women's Hospital, NRB 160,

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“…A limitation of this approach is that for individual genes there may be too few known polymorphisms to estimate dN:dS or Dr:Dc ratios with sufficient accuracy. Therefore, the methods that identify functionally related groups of genes [7,8,23] will have more power to find evidence of adaptive evolution in patterns of divergence and polymorphism.…”

Section: Introductionmentioning

confidence: 99%

Testing the neutral theory of molecular evolution using genomic data: a comparison of the human and bovine transcriptome

et al. 2006

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-Despite growing evidence of rapid evolution in protein coding genes, the contribution of positive selection to intra-and interspecific differences in protein coding regions of the genome is unclear. We attempted to see if genes coding for secreted proteins and genes with narrow expression, specifically those preferentially expressed in the mammary gland, have diverged at a faster rate between domestic cattle (Bos taurus) and humans (Homo sapiens) than other genes and whether positive selection is responsible. Using a large data set, we identified groups of genes based on secretion and expression patterns and compared them for the rate of nonsynonymous (dN) and synonymous (dS) substitutions per site and the number of radical (Dr) and conservative (Dc) amino acid substitutions. We found evidence of rapid evolution in genes with narrow expression, especially for those expressed in the liver and mammary gland and for genes coding for secreted proteins. We compared common human polymorphism data with human-cattle divergence and found that genes with high evolutionary rates in human-cattle divergence also had a large number of common human polymorphisms. This argues against positive selection causing rapid divergence in these groups of genes. In most cases dN/dS ratios were lower in human-cattle divergence than in common human polymorphism presumably due to differences in the effectiveness of purifying selection between long-term divergence and short-term polymorphism.

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Inferring Nonneutral Evolution from Human-Chimp-Mouse Orthologous Gene Trios

Cited by 622 publications

References 19 publications

New Methods for Detecting Lineage-Specific Selection

New Methods for Detecting Lineage-Specific Selection

Expression studies of osteoglycin/mimecan (OGN) in the cochlea and auditory phenotype of Ogn-deficient mice

Testing the neutral theory of molecular evolution using genomic data: a comparison of the human and bovine transcriptome

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