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1.
A comparative description of mitochondrial DNA differentiation in selected avian and other vertebrate genera 总被引:14,自引:1,他引:13
Levels of mitochondrial DNA (mtDNA) sequence divergence between species
within each of several avian (Anas, Aythya, Dendroica, Melospiza, and
Zonotrichia) and nonavian (Lepomis and Hyla) vertebrate genera were
compared. An analysis of digestion profiles generated by 13-18 restriction
endonucleases indicates little overlap in magnitude of mtDNA divergence for
the avian versus nonavian taxa examined. In 55 interspecific comparisons
among the avian congeners, the fraction of identical fragment lengths (F)
ranged from 0.26 to 0.96 (F = 0.46), and, given certain assumptions, these
translate into estimates of nucleotide sequence divergence (p) ranging from
0.007 to 0.088; in 46 comparisons among the fish and amphibian congeners, F
values ranged from 0.00 to 0.36 (F = 0.09), yielding estimates of P greater
than 0.070. The small mtDNA distances among avian congeners are associated
with protein-electrophoretic distances (D values) less than approximately
0.2, while the mtDNA distances among assayed fish and amphibian congeners
are associated with D values usually greater than 0.4. Since the
conservative pattern of protein differentiation previously reported for
many avian versus nonavian taxa now appears to be paralleled by a
conservative pattern of mtDNA divergence, it seems increasingly likely that
many avian species have shared more recent common ancestors than have their
nonavian taxonomic counterparts. However, estimates of avian divergence
times derived from mtDNA- and protein-calibrated clocks cannot readily be
reconciled with some published dates based on limited fossil remains. If
the earlier paleontological interpretations are valid, then protein and
mtDNA evolution must be somewhat decelerated in birds. The empirical and
conceptual issues raised by these findings are highly analogous to those in
the long-standing debate about rates of molecular evolution and times of
separation of ancestral hominids from African apes.
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2.
The environmental contexts of the karstic hominin sites in South Africa have been established largely by means of faunal associations; taken together these data suggest a trend from relatively closed and more mesic to open, drier environments from about 3 to 1.5 Ma. Vrba argued for a major shift within this trend ca. 2.4-2.6 Ma, an influential proposal that posited links between bovid (and hominin) radiation in Africa and the intensification of Northern Hemisphere Glaciation. Yet faunal approaches often rely on habitat and feeding preferences of modern taxa that may differ from those of their extinct predecessors. Here we explore ways of extending 13C/12C data from fossil mammals beyond denoting “presence” or “absence” of C4 grasses using the evolution of open environments in South Africa as a case study. To do so we calculated the relative proportions of C3-, mixed-, and C4-feeding herbivores for all the hominin sites for which we have sufficient data based on 13C/12C analyses of fossil tooth enamel. The results confirm a general trend towards more open environments since 3 Ma, but they also emphasize a marked change to open grassy habitats in the latest Pliocene/early Pleistocene. Mean 13C/12C for large felids also mirrored this trend. 相似文献
3.
Luyt K Slade TP Dorward JJ Durant CF Wu Y Shigemoto R Mundell SJ Váradi A Molnár E 《Journal of neurochemistry》2007,100(3):822-840
GABA(B) receptors (GABA(B)Rs) are involved in early events during neuronal development. The presence of GABA(B)Rs in developing oligodendrocytes has not been established. Using immunofluorescent co-localization, we have identified GABA(B)R proteins in O4 marker-positive oligodendrocyte precursor cells (OPCs) in 4-day-old mouse brain periventricular white matter. In culture, OPCs, differentiated oligodendrocytes (DOs) and type 2 astrocytes (ASTs) express both the GABA(B1abcdf) and GABA(B2) subunits of the GABA(B)R. Using semiquantitative PCR analysis with GABA(B)R isoform-selective primers we found that the expression level of GABA(B1abd) was substantially higher in OPCs or ASTs than in DOs. In contrast, the GABA(B2) isoform showed a similar level of expression in OPCs and DOs, and a significantly higher level in ASTs. This indicates that the expression of GABA(B1) and GABA(B2) subunits are under independent control during oligodendroglial development. Activation of GABA(B)Rs using the selective agonist baclofen demonstrated that these receptors are functionally active and negatively coupled to adenylyl cyclase. Manipulation of GABA(B)R activity had no effect on OPC migration in a conventional agarose drop assay, whereas baclofen significantly increased OPC migration in a more sensitive transwell microchamber-based assay. Exposure of cultured OPCs to baclofen increased their proliferation, providing evidence for a functional role of GABA(B)Rs in oligodendrocyte development. The presence of GABA(B)Rs in developing oligodendrocytes provides a new mechanism for neuronal-glial interactions during development and may offer a novel target for promoting remyelination following white matter injury. 相似文献
4.
Alexandra Hauser-Kawaguchi Cornelia Tolg Teresa Peart Mark Milne Eva A. Turley Leonard G. Luyt 《Bioorganic & medicinal chemistry》2018,26(18):5194-5203
The receptor for hyaluronan mediated motility (RHAMM, gene name HMMR) belongs to a group of proteins that bind to hyaluronan (HA), a high-molecular weight anionic polysaccharide that has pro-angiogenic and inflammatory properties when fragmented. We propose to use a chemically synthesized, truncated version of the protein (706–767), 7?kDa RHAMM, as a target receptor in the screening of novel peptide-based therapeutic agents. Chemical synthesis by Fmoc-based solid-phase peptide synthesis, and optimization using pseudoprolines, results in RHAMM protein of higher purity and yield than synthesis by recombinant protein production. 7?kDa RHAMM was evaluated for its secondary structure, ability to bind the native ligand, HA, and its bioactivity. This 62-amino acid polypeptide replicates the HA binding properties of both native and recombinant RHAMM protein. Furthermore, tubulin-derived HA peptide analogues that bind to recombinant RHAMM and were previously reported to compete with HA for interactions with RHAMM, bind with a similar affinity and specificity to the 7?kDa RHAMM. Therefore, in terms of its key binding properties, the 7?kDa RHAMM mini-protein is a suitable replacement for the full-length recombinant protein. 相似文献
5.
Shavanthi Rajatileka David Odd Matthew T. Robinson Alexandra C. Spittle Louis Dwomoh Maggie Williams David Harding Miles Wagstaff Marie Owen Charlene Crosby Jared Ching Elek Molnár Karen Luyt Anikó Váradi 《Molecular neurobiology》2018,55(3):2013-2024
Preterm delivery is associated with neurodevelopmental impairment caused by environmental and genetic factors. Dysfunction of the excitatory amino acid transporter 2 (EAAT2) and the resultant impaired glutamate uptake can lead to neurological disorders. In this study, we investigated the role of single nucleotide polymorphisms (SNPs; g.-200C>A and g.-181A>C) in the EAAT2 promoter in susceptibility to brain injury and neurodisability in very preterm infants born at or before 32-week gestation. DNA isolated from newborns’ dried blood spots were used for pyrosequencing to detect both SNPs. Association between EAAT2 genotypes and cerebral palsy, cystic periventricular leukomalacia and a low developmental score was then assessed. The two SNPs were concordant in 89.4% of infants resulting in three common genotypes all carrying two C and two A alleles in different combinations. However, in 10.6% of cases, non-concordance was found, generating six additional rare genotypes. The A alleles at both loci appeared to be detrimental and consequently, the risk of developing cerebral palsy increased four- and sixfold for each additional detrimental allele at -200 and -181 bp, respectively. The two SNPs altered the regulation of the EAAT2 promoter activity and glutamate homeostasis. This study highlights the significance of glutamate in the pathogenesis of preterm brain injury and subsequent development of cerebral palsy and neurodevelopmental disabilities. Furthermore, the described EAAT2 SNPs may be an early biomarker of vulnerability to neurodisability and may aid the development of targeted treatment strategies. 相似文献
6.
We studied different genetic models and evaluation systems to select against a genetic disease with additive, recessive or polygenic inheritance in genetic conservation schemes. When using optimum contribution selection with a restriction on the rate of inbreeding (ΔF) to select against a disease allele, selection directly on DNA-genotypes is, as expected, the most efficient strategy. Selection for BLUP or segregation analysis breeding value estimates both need 1–2 generations more to halve the frequency of the disease allele, while these methods do not require knowledge of the disease mutation at the DNA level. BLUP and segregation analysis methods were equally efficient when selecting against a disease with single gene or complex polygene inheritance, i.e. knowledge about the mode of inheritance of the disease was not needed for efficient selection against the disease. Smaller schemes or schemes with a more stringent restriction on ΔF needed more generations to halve the frequency of the disease alleles or the fraction of diseased animals. Optimum contribution selection maintained ΔF at its predefined level, even when selection of females was at random. It is argued that in the investigated small conservation schemes with selection against a genetic defect, control of ΔF is very important. 相似文献
7.
Ghrelin is a 28-amino acid peptide hormone produced in the stomach. It binds to the growth hormone secretagogue receptor 1a (GHS-R1a), a class A G-protein-coupled receptor. In the present study, we describe the design, synthesis and characterization of a truncated, 18-amino acid analog of ghrelin conjugated to a fluorescent molecule, fluorocein isothiocyanate (FITC), through the addition of a lysine at its C terminus ([Dpr(octanoyl)(3), Lys(fluorescein)(19)]ghrelin(1-19)). Receptor binding affinity of this novel fluorescein-ghrelin(1-18) was similar to that of wild-type ghrelin and a synthetic GHS-R1a ligand, hexarelin. Live cell imaging in CHO/GHS-R1a cells demonstrated cell surface receptor labeling and internalization, and agonist activity of fluorescein-ghrelin(1-18) was confirmed by increased phosphorylation of ERK1/2. We also show that GHS-R1a protein is expressed primarily in the heart when compared to all other organs, suggesting high receptor density in the left ventricle. Finally, we demonstrate that fluorescein-ghrelin(1-18) binds specifically to heart tissue in situ, and its binding is displaced by both wt ghrelin and hexarelin. We have therefore developed a novel imaging probe, fluorescein-ghrelin(1-18), that can be used to image GHS-R1a in situ, for the purposes of investigating mechanisms of receptor trafficking or pharmacological agents that target GHS-R1a. 相似文献
8.
Comparisons of the molecular evolutionary process at rbcL and ndhF in the grass family (Poaceae) 总被引:2,自引:1,他引:1
We examine rate heterogeneity among evolutionary lineages of the grass
family at two plasmid loci, ndhF and rbcL, and we introduce a method to
determine whether patterns of rate heterogeneity are correlated between
loci. We show both that rates of synonymous evolution are heterogeneous
among grass lineages and that are heterogeneity is correlated between loci
at synonymous sites. At nonsynonymous sites, the pattern of rate
heterogeneity is not correlated between loci, primarily due to an aberrant
pattern of rate heterogeneity at nonsynonymous sites of rbcL. We compare
patterns of synonymous rate heterogeneity to predictors based on the
generation time effect and the speciation rate hypotheses. Although there
is some evidence for generation time effects, neither generation time
effects nor speciation rates appear to be sufficient to explain patterns of
rate heterogeneity in the grass plastid sequences.
相似文献
9.
Cornelia Tolg Sara R. Hamilton Lyndsey Morningstar Jing Zhang S. Zhang Kenneth V. Esguerra Patrick G. Telmer Len G. Luyt Rene Harrison James B. McCarthy Eva A. Turley 《The Journal of biological chemistry》2010,285(34):26461-26474
An oncogenic form of RHAMM (receptor for hyaluronan-mediated motility, mouse, amino acids 163–794 termed RHAMMΔ163) is a cell surface hyaluronan receptor and mitotic spindle protein that is highly expressed in aggressive human cancers. Its regulation of mitotic spindle integrity is thought to contribute to tumor progression, but the molecular mechanisms underlying this function have not previously been defined. Here, we report that intracellular RHAMMΔ163 modifies the stability of interphase and mitotic spindle microtubules through ERK1/2 activity. RHAMM−/− mouse embryonic fibroblasts exhibit strongly acetylated interphase microtubules, multi-pole mitotic spindles, aberrant chromosome segregation, and inappropriate cytokinesis during mitosis. These defects are rescued by either expression of RHAMM or mutant active MEK1. Mutational analyses show that RHAMMΔ163 binds to α- and β-tubulin protein via a carboxyl-terminal leucine zipper, but in vitro analyses indicate this interaction does not directly contribute to tubulin polymerization/stability. Co-immunoprecipitation and pulldown assays reveal complexes of RHAMMΔ163, ERK1/2-MEK1, and α- and β-tubulin and demonstrate direct binding of RHAMMΔ163 to ERK1 via a D-site motif. In vitro kinase analyses, expression of mutant RHAMMΔ163 defective in ERK1 binding in mouse embryonic fibroblasts, and blocking MEK1 activity collectively confirm that the effect of RHAMMΔ163 on interphase and mitotic spindle microtubules is mediated by ERK1/2 activity. Our results suggest a model wherein intracellular RHAMMΔ163 functions as an adaptor protein to control microtubule polymerization during interphase and mitosis as a result of localizing ERK1/2-MEK1 complexes to their tubulin-associated substrates. 相似文献
10.
Job B Bernheim A Beau-Faller M Camilleri-Broët S Girard P Hofman P Mazières J Toujani S Lacroix L Laffaire J Dessen P Fouret P;LG Investigators 《PloS one》2010,5(12):e15145