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  • 1
    Publication Date: 2012-06-06
    Description: Extraordinary single-cell diversity is generated in the vertebrate nervous system by the combinatorial expression of the clustered protocadherin genes (Pcdhα, -β, and -γ). This diversity is generated by a combination of stochastic promoter choice and alternative pre-mRNA splicing. Here we show that both the insulator-binding protein CTCF and the cohesin complex subunit Rad21 bind to two highly conserved DNA sequences, the first within and the second downstream of transcriptionally active Pcdhα promoters. Both CTCF and Rad21 bind to these sites in vitro and in vivo, this binding directly correlates with alternative isoform expression, and knocking down CTCF expression reduces alternative isoform expression. Remarkably, a similarly spaced pair of CTCF/Rad21 binding sites was identified within a distant enhancer element (HS5-1), which is required for normal levels of alternative isoform expression. We also identify an additional, unique regulatory role for cohesin, as Rad21 binds to another enhancer (HS7) independently of CTCF, and knockdown of Rad21 reduces expression of the constitutive, biallelically expressed Pcdhα isoforms αc1 and αc2. We propose that CTCF and the cohesin complex initiate and maintain Pcdhα promoter choice by mediating interactions between Pcdhα promoters and enhancers.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2001-02-22
    Description: We have constructed a physical map of the human genome by using a panel of 90 whole-genome radiation hybrids (the TNG panel) in conjunction with 40,322 sequence-tagged sites (STSs) derived from random genomic sequences as well as expressed sequences. Of 36,678 STSs on the TNG radiation hybrid map, only 3604 (9.8%) were absent from the unassembled draft sequence of the human genome. Of 20,030 STSs ordered on the TNG map as well as the assembled human genome draft sequence and the Celera assembled human genome sequence, 36% of the STSs had a discrepant order between the working draft sequence and the Celera sequence. The TNG map order was identical to one of the two sequence orders in 60% of these discrepant cases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olivier, M -- Aggarwal, A -- Allen, J -- Almendras, A A -- Bajorek, E S -- Beasley, E M -- Brady, S D -- Bushard, J M -- Bustos, V I -- Chu, A -- Chung, T R -- De Witte, A -- Denys, M E -- Dominguez, R -- Fang, N Y -- Foster, B D -- Freudenberg, R W -- Hadley, D -- Hamilton, L R -- Jeffrey, T J -- Kelly, L -- Lazzeroni, L -- Levy, M R -- Lewis, S C -- Liu, X -- Lopez, F J -- Louie, B -- Marquis, J P -- Martinez, R A -- Matsuura, M K -- Misherghi, N S -- Norton, J A -- Olshen, A -- Perkins, S M -- Perou, A J -- Piercy, C -- Piercy, M -- Qin, F -- Reif, T -- Sheppard, K -- Shokoohi, V -- Smick, G A -- Sun, W L -- Stewart, E A -- Fernando, J -- Tejeda -- Tran, N M -- Trejo, T -- Vo, N T -- Yan, S C -- Zierten, D L -- Zhao, S -- Sachidanandam, R -- Trask, B J -- Myers, R M -- Cox, D R -- R01 GM062628/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Feb 16;291(5507):1298-302.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stanford Human Genome Center, Stanford University School of Medicine, 975 California Avenue, Palo Alto, CA 94304, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11181994" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Chromosomes, Artificial, Bacterial ; Computational Biology ; Contig Mapping ; Databases, Factual ; *Genome, Human ; Human Genome Project ; Humans ; In Situ Hybridization, Fluorescence ; Physical Chromosome Mapping ; Polymerase Chain Reaction ; *Radiation Hybrid Mapping ; *Sequence Analysis, DNA ; Sequence Tagged Sites ; Software
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2009-09-29
    Description: Sexual antagonism, or conflict between the sexes, has been proposed as a driving force in both sex-chromosome turnover and speciation. Although closely related species often have different sex-chromosome systems, it is unknown whether sex-chromosome turnover contributes to the evolution of reproductive isolation between species. Here we show that a newly evolved sex chromosome contains genes that contribute to speciation in threespine stickleback fish (Gasterosteus aculeatus). We first identified a neo-sex chromosome system found only in one member of a sympatric species pair in Japan. We then performed genetic linkage mapping of male-specific traits important for reproductive isolation between the Japanese species pair. The neo-X chromosome contains loci for male courtship display traits that contribute to behavioural isolation, whereas the ancestral X chromosome contains loci for both behavioural isolation and hybrid male sterility. Our work not only provides strong evidence for a large X-effect on reproductive isolation in a vertebrate system, but also provides direct evidence that a young neo-X chromosome contributes to reproductive isolation between closely related species. Our data indicate that sex-chromosome turnover might have a greater role in speciation than was previously appreciated.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776091/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776091/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kitano, Jun -- Ross, Joseph A -- Mori, Seiichi -- Kume, Manabu -- Jones, Felicity C -- Chan, Yingguang F -- Absher, Devin M -- Grimwood, Jane -- Schmutz, Jeremy -- Myers, Richard M -- Kingsley, David M -- Peichel, Catherine L -- P50 HG002568/HG/NHGRI NIH HHS/ -- P50 HG002568-08/HG/NHGRI NIH HHS/ -- P50 HG02568/HG/NHGRI NIH HHS/ -- R01 GM071854/GM/NIGMS NIH HHS/ -- R01 GM071854-05/GM/NIGMS NIH HHS/ -- T32 GM07270/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Oct 22;461(7267):1079-83. doi: 10.1038/nature08441. Epub 2009 Sep 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19783981" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Size ; Crosses, Genetic ; Female ; *Genetic Speciation ; Hybridization, Genetic ; Infertility, Male/genetics ; Japan ; Male ; Mating Preference, Animal ; Oceans and Seas ; Pacific Ocean ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Reproduction/genetics/physiology ; Sex Characteristics ; Sex Chromosomes/*genetics ; Smegmamorpha/anatomy & histology/classification/*genetics/*physiology ; Social Isolation ; Y Chromosome/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 1991-10-18
    Description: The neurotransmitter serotonin (5HT) activates a variety of second messenger signaling systems and through them indirectly regulates the function of ion channels. Serotonin also activates ion channels directly, suggesting that it may also mediate rapid, excitatory responses. A complementary DNA clone containing the coding sequence of one of these rapidly responding channels, a 5HT3 subtype of the serotonin receptor, has been isolated by screening a neuroblastoma expression library for functional expression of serotonin-gated currents in Xenopus oocytes. The predicted protein product has many of the features shared by other members of the ligand-gated ion channel family. The pharmacological and electrophysiological characteristics of the cloned receptor are largely consistent with the properties of native 5HT3 receptors. Messenger RNA encoding this receptor is found in the brain, spinal cord, and heart. This receptor defines a new class of excitatory ligand-gated channels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maricq, A V -- Peterson, A S -- Brake, A J -- Myers, R M -- Julius, D -- GM44298/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1991 Oct 18;254(5030):432-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of California, San Francisco 94143-0450.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1718042" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Binding, Competitive ; Cell Line ; Ion Channels/*chemistry/drug effects/physiology ; Mice ; Molecular Sequence Data ; Oocytes/metabolism ; Poly A ; RNA, Messenger ; Radioligand Assay ; Receptors, Serotonin/*chemistry/drug effects/physiology ; Xenopus
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 1990-04-13
    Description: Biosynthetic studies of the prion protein (PrP) have shown that two forms of different topology can be generated from the same pool of nascent chains in cell-free translation systems supplemented with microsomal membranes. A transmembrane form is the predominant product generated in wheat germ (WG) extracts, whereas a completely translocated (secretory) form is the major product synthesized in rabbit reticulocyte lysates (RRL). An unusual topogenic sequence within PrP is now shown to direct this system-dependent difference. The actions of this topogenic sequence were independent of on-going translation and could be conferred to heterologous proteins by the engineering of a discrete set of codons. System-dependent topology conferred by addition of RRL to WG translation products suggests that this sequence interacts with one or more cytosolic factors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lopez, C D -- Yost, C S -- Prusiner, S B -- Myers, R M -- Lingappa, V R -- AG02132/AG/NIA NIH HHS/ -- NS14069/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1990 Apr 13;248(4952):226-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of California, San Francisco 94143.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1970195" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Codon ; Cricetinae ; DNA, Viral/genetics ; Kinetics ; Mesocricetus ; Peptide Mapping ; Plasmids ; PrPSc Proteins ; Prions/*genetics ; Protein Biosynthesis ; Protein Processing, Post-Translational ; Restriction Mapping ; Transcription, Genetic ; Viral Proteins/biosynthesis/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 1990-10-12
    Description: Radiation hybrid (RH) mapping, a somatic cell genetic technique, was developed as a general approach for constructing long-range maps of mammalian chromosomes. This statistical method depends on x-ray breakage of chromosomes to determine the distances between DNA markers, as well as their order on the chromosome. In addition, the method allows the relative likelihoods of alternative marker orders to be determined. The RH procedure was used to map 14 DNA probes from a region of human chromosome 21 spanning 20 megabase pairs. The map was confirmed by pulsed-field gel electrophoretic analysis. The results demonstrate the effectiveness of RH mapping for constructing high-resolution, contiguous maps of mammalian chromosomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cox, D R -- Burmeister, M -- Price, E R -- Kim, S -- Myers, R M -- New York, N.Y. -- Science. 1990 Oct 12;250(4978):245-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry, University of California, San Francisco 94143.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2218528" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Chromosome Mapping ; Chromosomes/radiation effects ; Chromosomes, Human/radiation effects ; Chromosomes, Human, Pair 21 ; Genetic Markers ; Genetic Techniques ; Humans ; Hybrid Cells/cytology ; Mammals/*genetics ; Nucleic Acid Hybridization ; Restriction Mapping ; X-Rays
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2007-06-02
    Description: In vivo protein-DNA interactions connect each transcription factor with its direct targets to form a gene network scaffold. To map these protein-DNA interactions comprehensively across entire mammalian genomes, we developed a large-scale chromatin immunoprecipitation assay (ChIPSeq) based on direct ultrahigh-throughput DNA sequencing. This sequence census method was then used to map in vivo binding of the neuron-restrictive silencer factor (NRSF; also known as REST, for repressor element-1 silencing transcription factor) to 1946 locations in the human genome. The data display sharp resolution of binding position [+/-50 base pairs (bp)], which facilitated our finding motifs and allowed us to identify noncanonical NRSF-binding motifs. These ChIPSeq data also have high sensitivity and specificity [ROC (receiver operator characteristic) area 〉/= 0.96] and statistical confidence (P 〈10(-4)), properties that were important for inferring new candidate interactions. These include key transcription factors in the gene network that regulates pancreatic islet cell development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, David S -- Mortazavi, Ali -- Myers, Richard M -- Wold, Barbara -- 5T32GM07616/GM/NIGMS NIH HHS/ -- U01 HG003162/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2007 Jun 8;316(5830):1497-502. Epub 2007 May 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Stanford University School of Medicine, Stanford, CA, 94305-5120, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17540862" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Amino Acid Motifs ; Binding Sites ; *Chromatin Immunoprecipitation ; DNA/*metabolism ; DNA-Binding Proteins/chemistry/*metabolism ; Gene Regulatory Networks ; *Genome, Human ; Humans ; Insulin-Secreting Cells/cytology/physiology ; MicroRNAs/genetics ; Neurons/physiology ; Promoter Regions, Genetic ; Protein Binding ; Repressor Proteins/chemistry/genetics/*metabolism ; Sensitivity and Specificity ; *Sequence Analysis, DNA ; Synaptic Transmission ; T-Lymphocytes/metabolism ; Transcription Factors/chemistry/genetics/*metabolism ; Transcription, Genetic ; Zinc Fingers
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2008-02-23
    Description: Human genetic diversity is shaped by both demographic and biological factors and has fundamental implications for understanding the genetic basis of diseases. We studied 938 unrelated individuals from 51 populations of the Human Genome Diversity Panel at 650,000 common single-nucleotide polymorphism loci. Individual ancestry and population substructure were detectable with very high resolution. The relationship between haplotype heterozygosity and geography was consistent with the hypothesis of a serial founder effect with a single origin in sub-Saharan Africa. In addition, we observed a pattern of ancestral allele frequency distributions that reflects variation in population dynamics among geographic regions. This data set allows the most comprehensive characterization to date of human genetic variation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Jun Z -- Absher, Devin M -- Tang, Hua -- Southwick, Audrey M -- Casto, Amanda M -- Ramachandran, Sohini -- Cann, Howard M -- Barsh, Gregory S -- Feldman, Marcus -- Cavalli-Sforza, Luigi L -- Myers, Richard M -- GM073059/GM/NIGMS NIH HHS/ -- GM28016/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Feb 22;319(5866):1100-4. doi: 10.1126/science.1153717.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305-5120, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18292342" target="_blank"〉PubMed〈/a〉
    Keywords: Africa South of the Sahara ; Animals ; Founder Effect ; Gene Frequency ; Genetic Drift ; *Genome, Human ; Haplotypes ; Heterozygote ; Humans ; Pan troglodytes/genetics ; Pedigree ; *Polymorphism, Single Nucleotide
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2009-12-17
    Description: The molecular mechanisms underlying major phenotypic changes that have evolved repeatedly in nature are generally unknown. Pelvic loss in different natural populations of threespine stickleback fish has occurred through regulatory mutations deleting a tissue-specific enhancer of the Pituitary homeobox transcription factor 1 (Pitx1) gene. The high prevalence of deletion mutations at Pitx1 may be influenced by inherent structural features of the locus. Although Pitx1 null mutations are lethal in laboratory animals, Pitx1 regulatory mutations show molecular signatures of positive selection in pelvic-reduced populations. These studies illustrate how major expression and morphological changes can arise from single mutational leaps in natural populations, producing new adaptive alleles via recurrent regulatory alterations in a key developmental control gene.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109066/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109066/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chan, Yingguang Frank -- Marks, Melissa E -- Jones, Felicity C -- Villarreal, Guadalupe Jr -- Shapiro, Michael D -- Brady, Shannon D -- Southwick, Audrey M -- Absher, Devin M -- Grimwood, Jane -- Schmutz, Jeremy -- Myers, Richard M -- Petrov, Dmitri -- Jonsson, Bjarni -- Schluter, Dolph -- Bell, Michael A -- Kingsley, David M -- P50 HG002568/HG/NHGRI NIH HHS/ -- P50 HG002568-09/HG/NHGRI NIH HHS/ -- P50 HG02568/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Jan 15;327(5963):302-5. doi: 10.1126/science.1182213. Epub 2009 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20007865" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; *Biological Evolution ; Chromosome Fragile Sites ; Chromosome Mapping ; Crosses, Genetic ; DNA, Intergenic ; *Enhancer Elements, Genetic ; Fish Proteins/*genetics ; Molecular Sequence Data ; Mutation ; Paired Box Transcription Factors/*genetics ; Pelvis/anatomy & histology ; Selection, Genetic ; *Sequence Deletion ; Smegmamorpha/*anatomy & histology/*genetics/growth & development
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2005-03-26
    Description: Major phenotypic changes evolve in parallel in nature by molecular mechanisms that are largely unknown. Here, we use positional cloning methods to identify the major chromosome locus controlling armor plate patterning in wild threespine sticklebacks. Mapping, sequencing, and transgenic studies show that the Ectodysplasin (EDA) signaling pathway plays a key role in evolutionary change in natural populations and that parallel evolution of stickleback low-plated phenotypes at most freshwater locations around the world has occurred by repeated selection of Eda alleles derived from an ancestral low-plated haplotype that first appeared more than two million years ago. Members of this clade of low-plated alleles are present at low frequencies in marine fish, which suggests that standing genetic variation can provide a molecular basis for rapid, parallel evolution of dramatic phenotypic change in nature.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Colosimo, Pamela F -- Hosemann, Kim E -- Balabhadra, Sarita -- Villarreal, Guadalupe Jr -- Dickson, Mark -- Grimwood, Jane -- Schmutz, Jeremy -- Myers, Richard M -- Schluter, Dolph -- Kingsley, David M -- 1P50HG02568/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2005 Mar 25;307(5717):1928-33.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305-5329, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15790847" target="_blank"〉PubMed〈/a〉
    Keywords: *Alleles ; Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; *Biological Evolution ; Body Patterning ; Chromosome Walking ; Cloning, Molecular ; Ectodysplasins ; Fresh Water ; Gene Frequency ; Genetic Variation ; Haplotypes ; Linkage Disequilibrium ; Membrane Proteins/*genetics/physiology ; Molecular Sequence Data ; Mutation ; Phenotype ; Phylogeny ; Polymorphism, Single Nucleotide ; Seawater ; Selection, Genetic ; Sequence Analysis, DNA ; Signal Transduction ; Smegmamorpha/*anatomy & histology/classification/*genetics/growth & development
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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