Abstract:
:Tandem gene duplication is an important mutational process in evolutionary adaptation and human disease. Hypothetically, two tandem gene copies should produce twice the output of a single gene, but this expectation has not been rigorously investigated. Here, we show that tandem duplication often results in more than double the gene activity. A naturally occurring tandem duplication of the Alcohol dehydrogenase (Adh) gene exhibits 2.6-fold greater expression than the single-copy gene in transgenic Drosophila This tandem duplication also exhibits greater activity than two copies of the gene in trans, demonstrating that it is the tandem arrangement and not copy number that is the cause of overactivity. We also show that tandem duplication of an unrelated synthetic reporter gene is overactive (2.3- to 5.1-fold) at all sites in the genome that we tested, suggesting that overactivity could be a general property of tandem gene duplicates. Overactivity occurs at the level of RNA transcription, and therefore tandem duplicate overactivity appears to be a previously unidentified form of position effect. The increment of surplus gene expression observed is comparable to many regulatory mutations fixed in nature and, if typical of other genomes, would shape the fate of tandem duplicates in evolution.
journal_name
Proc Natl Acad Sci U S Aauthors
Loehlin DW,Carroll SBdoi
10.1073/pnas.1605886113subject
Has Abstractpub_date
2016-05-24 00:00:00pages
5988-92issue
21eissn
0027-8424issn
1091-6490pii
1605886113journal_volume
113pub_type
杂志文章abstract::Probing a wide range of cellular phenotypes in neurodevelopmental disorders using patient-derived neural progenitor cells (NPCs) can be facilitated by 3D assays, as 2D systems cannot entirely recapitulate the arrangement of cells in the brain. Here, we developed a previously unidentified 3D migration and differentiati...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1521255113
更新日期:2016-03-22 00:00:00
abstract::Band 3, the major intrinsic protein of the human erythrocyte membrane, was specifically labeled with the covalent fluorescent probe eosin isothiocyanate. The lateral mobility of labeled band 3 in the plane of the membrane under various conditions of ionic strength and temperature was examined by using the fluorescence...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.5.2537
更新日期:1980-05-01 00:00:00
abstract::With the completion of genome sequences of major model organisms, increasingly sophisticated genetic tools are necessary for investigating the complex and coordinated functions of genes. Here we describe a genetic manipulation system termed "genomic engineering" in Drosophila. Genomic engineering is a 2-step process t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0900641106
更新日期:2009-05-19 00:00:00
abstract::Peptide-protein interactions are important mediators of cellular-signaling events. Consensus binding motifs (also known as short linear motifs) within these contacts underpin molecular recognition, yet have poor pharmacological properties as discrete species. Here, we present methods to transform intact peptides into ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1311706110
更新日期:2013-10-01 00:00:00
abstract::Six independent lines of evidence point to the existence of heme-containing compounds and/or hemoglobin breakdown products in extracts of trabecular tissues of the large theropod dinosaur Tyrannosaurus rex. These include signatures from nuclear magnetic resonance and electron spin resonance that indicate the presence ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.12.6291
更新日期:1997-06-10 00:00:00
abstract::We report the isolation and functional characterization of cDNAs encoding a Drosophila kainate-selective glutamate receptor. The deduced mature 964-residue protein (DGluR-I) is 108,482 Da and exhibits significant homology to mammalian glutamate receptor subunits. Injection of DGluR-I cRNA into Xenopus oocytes generate...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.21.10484
更新日期:1992-11-01 00:00:00
abstract::We determined the genomic sequence at the site of insertion in 2,266 unselected P element insertion events. Estimating physical properties of the genomic DNA at these insertion sites-such as base composition, bendability, A-philicity, protein-induced deformability, and B-DNA twist-revealed that they differ significant...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.050017397
更新日期:2000-03-28 00:00:00
abstract::In addition to guiding proteins to defined genomic loci, DNA can act as an allosteric ligand that influences protein structure and activity. Here we compared genome-wide binding, transcriptional regulation, and, using NMR, the conformation of two glucocorticoid receptor (GR) isoforms that differ by a single amino acid...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1316235110
更新日期:2013-10-29 00:00:00
abstract::Animal studies have shown that the brain is an insulin-responsive organ and that central nervous insulin resistance induces obesity and disturbances in glucose metabolism. In humans, insulin effects in the brain are poorly characterized. We used a magnetoencephalography approach during a two-step hyperinsulinemic eugl...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0604404103
更新日期:2006-08-08 00:00:00
abstract::A full-length cDNA for tryptophan hydroxylase was cloned from rabbit pineal body by screening an expression library with antibody against rat phenylalanine hydroxylase, which crossreacts with rabbit tryptophan hydroxylase. Clones producing immunoreactive material contain sequences homologous to, yet distinct from, phe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.16.5530
更新日期:1987-08-01 00:00:00
abstract::The endosperm of cereal grains is one of the most valuable products of modern agriculture. Cereal endosperm development comprises different phases characterized by mitotic cell proliferation, endoreduplication, the accumulation of storage compounds, and programmed cell death. Although manipulation of these processes c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1304903110
更新日期:2013-05-07 00:00:00
abstract::Platelet factor 4 is shown to be a chemotactic protein for human polymorphonuclear leukocytes and monocytes at concentrations found in human serum and reached locally in injured tissue. The maximum chemotactic response to platelet factor 4 nearly equals that achieved with saturating concentrations of the chemotactic a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.7.4584
更新日期:1981-07-01 00:00:00
abstract::Urodeles and fetal mammals are capable of impressive epimorphic regeneration in a variety of tissues, whereas the typical default response to injury in adult mammals consists of inflammation and scar tissue formation. One component of epimorphic regeneration is the recruitment of resident progenitor and stem cells to ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0905851106
更新日期:2010-02-23 00:00:00
abstract::We have shown that a scanning transmission electron microscope with a high brightness field emission source is capable of obtaining better than 3 A resolution using 30 to 40 keV electrons. Elastic dark field images of single atoms of uranium and mercury are shown which demonstrate this fact as determined by a modified...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.71.1.1
更新日期:1974-01-01 00:00:00
abstract::T cells transferred into severe lymphopenic hosts undergo rapid proliferation known as "endogenous proliferation" that are distinct from conventional homeostatic proliferation. Unlike homeostatic proliferation, cytokines, such as IL-7 are dispensable, yet TCR:MHC interaction is essential for this process to occur. How...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0909954106
更新日期:2009-12-01 00:00:00
abstract::In over 90% of cervical cancers and cancer-derived cell lines, the p53 tumor suppressor pathway is disrupted by human papillomavirus (HPV). The HPV E6 protein promotes the degradation of p53 and thus inhibits the stabilization and activation of p53 that would normally occur in response to HPV E7 oncogene expression. R...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.15.8501
更新日期:2000-07-18 00:00:00
abstract::A protein that specifically binds leukemia inhibitory factor (LIF) has been isolated from normal mouse serum by using four successive fractionation steps: chromatography on a LIF affinity matrix, anion-exchange chromatography, size-exclusion chromatography, and preparative native gel electrophoresis. The purified LIF-...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.18.8616
更新日期:1992-09-15 00:00:00
abstract::The levels of the neural axis from which parasympathetic and orthosympathetic neurons and adrenomedullary cells are derived under normal developmental conditions were determined in avian embryos by a biological labeling technique. The technique is based on nuclear differences between two species of birds, the chick an...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.2.728
更新日期:1975-02-01 00:00:00
abstract::Forkhead box g1 (Foxg1) is a nuclear-cytosolic transcription factor essential for the forebrain development and involved in neurodevelopmental and cancer pathologies. Despite the importance of this protein, little is known about the modalities by which it exerts such a large number of cellular functions. Here we show ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1515190112
更新日期:2015-11-10 00:00:00
abstract::One of the defining trends of the Holocene has been the emergence of complex societies. Two essential features of complex societies are intensive resource use and sociopolitical hierarchy. Although it is widely agreed that these two phenomena are associated cross-culturally and have both contributed to the rise of com...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1714558115
更新日期:2018-04-03 00:00:00
abstract::We have used a semiselective Hahn spin-echo sequence of the form (1331)-tau-(2662)-tau-AQ, delivered by a surface coil to obtain high-resolution 1H NMR spectra from the brains of intact dead rats. This sequence gave suppression of the tissue water resonance by a factor of 80,000 when tau = 68 ms. Delivery of a frequen...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.10.3115
更新日期:1985-05-01 00:00:00
abstract::The complexed (ribosome-bearing) membrane fraction of Bacillus subtilis contains several proteins (CM-proteins) that are virtually absent from the ribosome-free fraction and hence might be components of the apparatus of protein secretion. We have determined, by trypsin digestion and by labeling with a nonpenetrating r...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.11.3287
更新日期:1983-06-01 00:00:00
abstract::The recent observation of superconductivity in [Formula: see text] has raised fundamental questions about the hierarchy of the underlying electronic structure. Calculations suggest that this system falls in the Mott-Hubbard regime, rather than the charge-transfer configuration of other nickel oxides and the supercondu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2007683118
更新日期:2021-01-12 00:00:00
abstract::Mutations in the thyroid hormone receptor α 1 gene (THRA) have recently been identified as a cause of intellectual deficit in humans. Patients present with structural abnormalities including microencephaly, reduced cerebellar volume and decreased axonal density. Here, we show that directed differentiation of THRA muta...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1908762116
更新日期:2019-11-05 00:00:00
abstract::Deleting an important active-site residue of diphtheria toxin, glutamic acid-148, reduces the toxin's ADP-ribosyltransferase activity by a factor of greater than 10(4). We considered using this mutation to construct a recombinant toxoid for expression by live attenuated vaccines and explored second-site mutations that...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.13.6207
更新日期:1992-07-01 00:00:00
abstract::Charcot-Marie-Tooth disease type 4C (CMT4C) is an early-onset, autosomal recessive form of demyelinating neuropathy. The clinical manifestations include progressive scoliosis, delayed age of walking, muscular atrophy, distal weakness, and reduced nerve conduction velocity. The gene mutated in CMT4C disease, SH3TC2/KIA...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0905523106
更新日期:2009-10-13 00:00:00
abstract::The semidwarf phenotype has been extensively selected during modern crop breeding as an agronomically important trait. Introduction of the semidwarf gene, semi-dwarf1 (sd1), which encodes a gibberellin biosynthesis enzyme, made significant contributions to the "green revolution" in rice (Oryza sativa L.). Here we repo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1019490108
更新日期:2011-07-05 00:00:00
abstract::Parvalbumin (PV) is a Ca2+-binding protein found only in vertebrates. It is postulated to serve as a soluble relaxing factor in fast mammalian muscle. We have isolated a rat PV cDNA clone and used this as a probe to examine changes in PV mRNA during muscle and brain development. A cDNA library was constructed in PUC8/...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.5.1414
更新日期:1985-03-01 00:00:00
abstract::Recent expeditions to the Fayum Depression, Egypt, have made possible the discovery of mandibles and a maxilla of a new genus and species of late Eocene elephant-shrew as well as initial evidence of the upper dentition of the early Oligocene taxon Metoldobotes. These fossils demonstrate that macroscelideans underwent ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.21.9734
更新日期:1991-11-01 00:00:00
abstract::Zeolite and zeolite-like molecular sieves are being used in a large number of applications such as adsorption and catalysis. Achievement of the long-standing goal of creating a chiral, polycrystalline molecular sieve with bulk enantioenrichment would enable these materials to perform enantioselective functions. Here, ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1704638114
更新日期:2017-05-16 00:00:00