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Search Results: 1 - 10 of 551 matches for " Doron Lancet "
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Conservation anchors in the vertebrate genome
Ronny Aloni, Doron Lancet
Genome Biology , 2005, DOI: 10.1186/gb-2005-6-7-115
Abstract: One of the most exciting recent outcomes of comparative genomics is the realization that when two or more vertebrate genomes are compared via phylogenetic footprinting, numerous highly similar non-coding segments emerge [1-4]. Many acronyms have been proposed for such highly conserved segments (Table 1); here they are referred to as ANCORs (ancestral non-coding conserved regions). Several recent papers address this topic in new ways, and refer to the origin and potential function of such conserved sequences.Initially, small-scale analyses comparing human and mouse (or other species) suggested conservation outside coding regions [5,6]. The identification of such conservation in the vicinity of specific genes (in proximal flanking regions, untranslated regions or UTRs, and introns) helped in the exploration of corresponding regulatory regions. Somewhat broader studies suggested sequence conservation in large sets of orthologous pairs [3,7,8]. The advent of full genomic sequences of human [9] and mouse [10] allowed the first large-scale analyses not limited to gene-related regions. A comparison between human chromosome 21 and the syntenic region in mouse [11] revealed a significant number of noncoding conserved elements, many of them far from gene-coding regions [12].Different reports use not only different nomenclature, but also different definitions in terms of compared species, ANCOR length, and percentage identity. We propose to unite these parameters by using a labeling system that refers to frequency within the genome (Figure 1), a property that follows from any filtering process. Thus, for example, segments defined as being within the top 5% of interspecies conservation [13] will be denoted here as ANCOR5%, while much more highly conserved 250 base-pair (bp) segments, which have a count of only 256 within 3 × 109 bp of human-rodent sequence [14], have an incidence of 0.002% and are therefore labeled ANCOR0.002% (see Additional data file 1). Thus, different repor
Ancient genomic architecture for mammalian olfactory receptor clusters
Ronny Aloni, Tsviya Olender, Doron Lancet
Genome Biology , 2006, DOI: 10.1186/gb-2006-7-10-r88
Abstract: We developed a new and general tool for genome-wide definition of genomic gene clusters conserved in multiple species. Syntenic orthologs, defined as gene pairs showing conservation of both genomic location and coding sequence, were subjected to a graph theory algorithm for discovering CLICs (clusters in conservation). When applied to ORs in five mammals, including the marsupial opossum, more than 90% of the OR genes were found within a framework of 48 multi-species CLICs, invoking a general conservation of gene order and composition. A detailed analysis of individual CLICs revealed multiple differences among species, interpretable through species-specific genomic rearrangements and reflecting complex mammalian evolutionary dynamics. One significant instance involves CLIC #1, which lacks a human member, implying the human-specific deletion of an OR cluster, whose mouse counterpart has been tentatively associated with isovaleric acid odorant detection.The identified multi-species CLICs demonstrate that most of the mammalian OR clusters have a common ancestry, preceding the split between marsupials and placental mammals. However, only two of these CLICs were capable of incorporating chicken OR genes, parsimoniously implying that all other CLICs emerged subsequent to the avian-mammalian divergence.Olfactory receptor (OR) genes constitute the largest superfamily in the vertebrate genome, with several hundred genes per species [1-3]. This large repertoire of receptors mediates the sense of smell through the recognition of diverse volatile molecules, used to detect food, predators, and mates. Mammalian OR genes reside in about 50 genomic clusters of one to several dozen genes, which are dispersed among many chromosomes [4,5]. Although the number of clusters is similar among species, the typical cluster size varies significantly because of extensive lineage-specific evolutionary events (for example, inter- and intra-chromosomal gene duplications and genomic deletions) [3,6
Spontaneous chiral symmetry breaking in early molecular networks
Ran Kafri, Omer Markovitch, Doron Lancet
Biology Direct , 2010, DOI: 10.1186/1745-6150-5-38
Abstract: We propose here a more general kinetic formalism for early enantioselection, based on our previously described Graded Autocatalysis Replication Domain (GARD) model for prebiotic evolution in molecular assemblies. This model is adapted here to the case of chiral molecules by applying symmetry constraints to mutual molecular recognition within the assembly. The ensuing dynamics shows spontaneous chiral symmetry breaking, with transitions towards stationary compositional states (composomes) enriched with one of the two enantiomers for some of the constituent molecule types. Furthermore, one or the other of the two antipodal compositional states of the assembly also shows time-dependent selection.It follows that chiral selection may be an emergent consequence of early catalytic molecular networks rather than a prerequisite for the initiation of primeval life processes. Elaborations of this model could help explain the prevalent chiral homogeneity in present-day living cells.This article was reviewed by Boris Rubinstein (nominated by Arcady Mushegian), Arcady Mushegian, Meir Lahav (nominated by Yitzhak Pilpel) and Sergei Maslov.The derivation of chemical reactions that spontaneously generate an excess of one enantiomeric form (i.e. one of two stereo-isomers of an asymmetric molecule endowed with the property of handedness or chirality, and mutually related by mirror symmetry) has been a central ambition of numerous theoretical and experimental studies [1-6]. The challenge is to depart from a racemic mixtures (having equal amounts of both isomers), and reach enantiomeric excess without the aid of external chiral selectors. Thus (reviewed in [5]), some authors have proposed that a catastrophic symmetry breaking event was necessary to explain why in a class of biomolecules (e.g. amino acids) all members have the same chiral configuration. Energy imbalance of enantiomers due to a lack of antimatter parity, or enantioselective breakdown by circularly polarized light from spac
A probabilistic classifier for olfactory receptor pseudogenes
Idan Menashe, Ronny Aloni, Doron Lancet
BMC Bioinformatics , 2006, DOI: 10.1186/1471-2105-7-393
Abstract: To characterize inactive ORs with intact open reading frame, we have developed a probabilistic Classifier for Olfactory Receptor Pseudogenes (CORP). This algorithm is based on deviations from a functionally crucial consensus, constituting sixty highly conserved positions identified by a comparison of two evolutionarily-constrained OR repertoires (mouse and dog) with a small pseudogene fraction. We used a logistic regression analysis to assign appropriate coefficients to the conserved position and thus achieving maximal separation between active and inactive ORs. Consequently, the algorithms identified only 5% of the mouse functional ORs as pseudogenes, setting an upper limit of 0.05 to the false positive detection. Finally we used this algorithm to classify the 384 purportedly intact human OR genes. Of these, 135 were predicted as likely encoding non-functional proteins, and 38 were segregating between active and inactive forms due to missense polymorphisms.We demonstrated that the CORP algorithm is capable to distinguish between functional and non-functional OR genes with high precision even when the encoded protein would differ by a single amino acid. Using the CORP algorithm, we predict that ~70% of human OR genes are likely non-functional pseudogenes, a much higher number than hitherto suspected. The method we present may be employed for better annotation of inactive members in other gene families as well.CORP algorithm is available at: http://bioportal.weizmann.ac.il/HORDE/CORP/ webcitePseudogenes, non-functional gene relics, are highly abundant genome-wide, with an estimated count of at least ~20,000 in the human genome [1,2]. A majority of these (~70%), are processed pseudogenes generated by reverse transcription of mRNAs followed by random genomic integration and thus, resulting in promoter region loss. The remainder non-processed pseudogenes are the result of gene duplication followed by mutational inactivation of one of the redundant copies. Pseudogenes ar
Update on the olfactory receptor (OR) gene superfamily
Tsviya Olender, Doron Lancet, Daniel W Nebert
Human Genomics , 2008, DOI: 10.1186/1479-7364-3-1-87
Abstract: Before 1980, the names of genes and classification of their encoded proteins were highly variable and non-systematic -- especially to anyone slightly outside a particular field or to a new graduate student entering the field. Professor Margaret Oakley Dayhoff was a pioneer in attempting to create order out of chaos in the naming of genes and gene families by means of computerised protein alignments [1]. She was widely recognised as the founder in this new field of gene/protein classification, before her untimely death in 1983.Cytochrome P450 (CYP) genes are conveniently arranged into families and subfamilies based on the percentage amino acid sequence identity [2-7]. Enzymes that share approximately ≥ 40 per cent identity are assigned to a particular family designated by an Arabic numeral, whereas those sharing approximately ≥ 55 per cent identity are grouped into a particular subfamily designated by a letter. For example, the sterol 27-hydroxylase enzyme and the 25-hydroxy-vitamin D3 1α-hydroxylase enzyme are both assigned to the CYP27 family because they share > 40 per cent sequence identity. Furthermore, the sterol 27-hydroxylase is assigned to the CYP27 'A' subfamily and the 25-hydroxy-vitamin D3 1 α-hydroxylase to the CYP27 'B' subfamily because their protein sequences are < 55 per cent identical. If an additional enzyme were to be discovered that shared > 55 per cent identity with the sterol 27-hydroxylase, then it would be named CYP27A2. If an additional enzyme were to be discovered that shared < 55 per cent but > 40 per cent identity with the sterol 27-hydroxylase as well as the 25-hydroxy-vitamin D3 1α-hydroxylase, then it would be named CYP27C1. The development and application of this delightfully logical system of nomenclature to the genes of many animals, plants and bacteria [8] has eliminated the confusion that often had plagued the naming of gene families and superfamilies. Subsequently, this 'divergent evolution' nomenclature system was adopted for se
Common peptides shed light on evolution of Olfactory Receptors
Assaf Gottlieb, Tsviya Olender, Doron Lancet, David Horn
BMC Evolutionary Biology , 2009, DOI: 10.1186/1471-2148-9-91
Abstract: We extract deterministic motifs from ORs belonging to ten species using the MEX (Motif Extraction) algorithm, thus defining Common Peptides (CPs) characteristic to ORs. We identify species-specific CPs and show that their relative abundance is high only in fish and frog, suggesting relevance to water-soluble odorants. We estimate the origins of CPs according to the tree of life and track the gains and losses of CPs through evolution. We identify major CP gain in tetrapods and major losses in reptiles. Although the number of human ORs is less than half of the number of ORs in other mammals, the fraction of lost CPs is only 11%.By examining the positions of CPs along the OR sequence, we find two regions that expanded only in tetrapods. Using CPs we are able to establish remote homology relations between ORs and non-OR GPCRs.Selecting CPs according to their evolutionary age, we bicluster ORs and CPs for each species. Clean biclustering emerges when using relatively novel CPs. Evolutionary age is used to track the history of CP acquisition in the collection of mammalian OR families within HORDE (Human Olfactory Receptor Data Explorer).The CP method provides a novel perspective that reveals interesting traits in the evolution of olfactory receptors. It is consistent with previous knowledge, and provides finer details. Using available phylogenetic trees, evolution can be rephrased in terms of CP origins.Supplementary information is also available at http://adios.tau.ac.il/ORPS webciteOdor recognition in vertebrates is mediated by a large superfamily of olfactory receptor (OR) genes, G-protein coupled receptors (GPCRs) with seven trans-membrane domains [1,2]. Whole genome studies discovered hundreds of intact ORs in the vertebrate genome, ranging in size from ~100 in fishes to ~1000 in mouse [3-5] and [6].A recent study of OR evolutionary dynamics indicated the existence of nine ancestral genes common to fish and tetrapods, of which only two are found in birds and mammals.
Correction: Loss of Olfactory Receptor Genes Coincides with the Acquisition of Full Trichromatic Vision in Primates
Yoav Gilad,Victor Wiebe,Molly Przeworski,Doron Lancet,Svante P??bo
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0050148
Loss of Olfactory Receptor Genes Coincides with the Acquisition of Full Trichromatic Vision in Primates
Yoav Gilad,Victor Wiebe,Molly Przeworski,Doron Lancet,Svante P??bo
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0020005
Abstract: Olfactory receptor (OR) genes constitute the molecular basis for the sense of smell and are encoded by the largest gene family in mammalian genomes. Previous studies suggested that the proportion of pseudogenes in the OR gene family is significantly larger in humans than in other apes and significantly larger in apes than in the mouse. To investigate the process of degeneration of the olfactory repertoire in primates, we estimated the proportion of OR pseudogenes in 19 primate species by surveying randomly chosen subsets of 100 OR genes from each species. We find that apes, Old World monkeys and one New World monkey, the howler monkey, have a significantly higher proportion of OR pseudogenes than do other New World monkeys or the lemur (a prosimian). Strikingly, the howler monkey is also the only New World monkey to possess full trichromatic vision, along with Old World monkeys and apes. Our findings suggest that the deterioration of the olfactory repertoire occurred concomitant with the acquisition of full trichromatic color vision in primates.
Genetic Elucidation of Human Hyperosmia to Isovaleric Acid
Idan Menashe,Tatjana Abaffy,Yehudit Hasin,Sivan Goshen,Vered Yahalom,Charles W. Luetje,Doron Lancet
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0050284
Abstract: The genetic basis of odorant-specific variations in human olfactory thresholds, and in particular of enhanced odorant sensitivity (hyperosmia), remains largely unknown. Olfactory receptor (OR) segregating pseudogenes, displaying both functional and nonfunctional alleles in humans, are excellent candidates to underlie these differences in olfactory sensitivity. To explore this hypothesis, we examined the association between olfactory detection threshold phenotypes of four odorants and segregating pseudogene genotypes of 43 ORs genome-wide. A strong association signal was observed between the single nucleotide polymorphism variants in OR11H7P and sensitivity to the odorant isovaleric acid. This association was largely due to the low frequency of homozygous pseudogenized genotype in individuals with specific hyperosmia to this odorant, implying a possible functional role of OR11H7P in isovaleric acid detection. This predicted receptor–ligand functional relationship was further verified using the Xenopus oocyte expression system, whereby the intact allele of OR11H7P exhibited a response to isovaleric acid. Notably, we also uncovered another mechanism affecting general olfactory acuity that manifested as a significant inter-odorant threshold concordance, resulting in an overrepresentation of individuals who were hyperosmic to several odorants. An involvement of polymorphisms in other downstream transduction genes is one possible explanation for this observation. Thus, human hyperosmia to isovaleric acid is a complex trait, contributed to by both receptor and other mechanisms in the olfactory signaling pathway.
GIFtS: annotation landscape analysis with GeneCards
Arye Harel, Aron Inger, Gil Stelzer, Liora Strichman-Almashanu, Irina Dalah, Marilyn Safran, Doron Lancet
BMC Bioinformatics , 2009, DOI: 10.1186/1471-2105-10-348
Abstract: We present the GeneCards Inferred Functionality Score (GIFtS) which allows a quantitative assessment of a gene's annotation status, by exploiting the unique wealth and diversity of GeneCards information. The GIFtS tool, linked from the GeneCards home page, facilitates browsing the human genome by searching for the annotation level of a specified gene, retrieving a list of genes within a specified range of GIFtS value, obtaining random genes with a specific GIFtS value, and experimenting with the GIFtS weighting algorithm for a variety of annotation categories. The bimodal shape of the GIFtS distribution suggests a division of the human gene repertoire into two main groups: the high-GIFtS peak consists almost entirely of protein-coding genes; the low-GIFtS peak consists of genes from all of the categories. Cluster analysis of GIFtS annotation vectors provides the classification of gene groups by detailed positioning in the annotation arena. GIFtS also provide measures which enable the evaluation of the databases that serve as GeneCards sources. An inverse correlation is found (for GIFtS>25) between the number of genes annotated by each source, and the average GIFtS value of genes associated with that source. Three typical source prototypes are revealed by their GIFtS distribution: genome-wide sources, sources comprising mainly highly annotated genes, and sources comprising mainly poorly annotated genes. The degree of accumulated knowledge for a given gene measured by GIFtS was correlated (for GIFtS>30) with the number of publications for a gene, and with the seniority of this entry in the HGNC database.GIFtS can be a valuable tool for computational procedures which analyze lists of large set of genes resulting from wet-lab or computational research. GIFtS may also assist the scientific community with identification of groups of uncharacterized genes for diverse applications, such as delineation of novel functions and charting unexplored areas of the human genome.In t
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