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81.
Substitution bias, rapid saturation, and the use of mtDNA for nematode systematics 总被引:13,自引:0,他引:13
Only relatively recently have researchers turned to molecular methods for
nematode phylogeny reconstruction. Thus, we lack the extensive literature
on evolutionary patterns and phylogenetic usefulness of different DNA
regions for nematodes that exists for other taxa. Here, we examine the
usefulness of mtDNA for nematode phylogeny reconstruction and provide data
that can be used for a priori character weighting or for parameter
specification in models of sequence evolution. We estimated the
substitution pattern for the mitochondrial ND4 gene from intraspecific
comparisons in four species of parasitic nematodes from the family
Trichostrongylidae (38-50 sequences per species). The resulting pattern
suggests a strong mutational bias toward A and T, and a lower
transition/transversion ratio than is typically observed in other taxa. We
also present information on the relative rates of substitution at first,
second, and third codon positions and on relative rates of saturation of
different types of substitutions in comparisons ranging from intraspecific
to interordinal. Silent sites saturate extremely quickly, presumably owing
to the substitution bias and, perhaps, to an accelerated mutation rate.
Results emphasize the importance of using only the most closely related
sequences in order to infer patterns of substitution accurately for
nematodes or for other taxa having strongly composition-biased DNA. ND4
also shows high amino acid polymorphism at both the intra- and
interspecific levels, and in higher level comparisons, there is evidence of
saturation at variable amino acid sites. In general, we recommend using
mtDNA coding genes only for phylogenetics of relatively closely related
nematode species and, even then, using only nonsynonymous substitutions and
the more conserved mitochondrial genes (e.g., cytochrome oxidases). On the
other hand, the high substitution rate in genes such as ND4 should make
them excellent for population genetics studies, identifying cryptic
species, and resolving relationships among closely related congeners when
other markers show insufficient variation.
相似文献
82.
Fucose is a major constituent of the protein- and lipid-linked glycans of
the various life-cycle stages of schistosomes. These fucosylated glycans
are highly antigenic and seem to play a role in the pathology of
schistosomiasis. In this article we describe the identification and
characterization of two fucosyltransferases (FucTs) in cercariae of the
avian schistosome Trichobilharzia ocellata, a GDP-Fuc:[Galbeta1--
>4]GlcNAcbeta-R alpha1-->3-FucT and a novel GDP-Fuc:Fucalpha-R
alpha1-- >2-FucT. Triton X-100 extracts of cercariae were assayed for
FucT activity using a variety of acceptor substrates. Type 1 chain
(Galbeta1- ->3GlcNAc) based compounds were poor acceptors, whereas those
based on a type 2 chain (Galbeta1-->4GlcNAc), whether
alpha2'-fucosylated, alpha3'-sialylated, or unsubstituted, and whether
present as oligosaccharide or contained in a glycopeptide or glycoprotein,
all served as acceptor substrates. In this respect the schistosomal alpha3-
FucT resembles human FucT V and VI rather than other known FucTs. N-
ethylmaleimide, an inhibitor of several human FucTs, had no effect on the
activity of the schistosomal alpha3-FucT, whereas GDP-beta-S was strongly
inhibitory. Large scale incubations were carried out with
Galbeta1-->4GlcNAc, GalNAcbeta1-->4GlcNAcbeta-O -(CH2)8COOCH3 and
Fucalpha1-->3GlcNAcbeta1-->2Man as acceptor substrates and the
products of the incubations were isolated using a sequence of
chromatographic techniques. By methylation analysis and 2D-TOCSY and
ROESY1H-NMR spectroscopy the products formed were shown to be Galbeta1--
>4[Fucalpha1-->2Fucalpha1-->3]GlcNAc,
GalNAcbeta1-->4[Fucalpha1-- >2Fucalpha1-->3]GlcNAcbe
ta-O-(CH2)8COOCH3, and Fucalpha1-->2Fucalpha1--
>3GlcNAcbeta1-->2Man, respectively. It is concluded that the alpha2-
FucT and alpha3-FucT are involved in the biosynthesis of the (oligomeric)
Lewisx sequences and the Fucalpha1-->2Fucalpha1-->3GlcNAc structural
element that have been described on schistosomal glycoconjugates.
相似文献
83.
Nuclear complementation restores mtDNA levels in cultured cells from a patient with mtDNA depletion. 总被引:10,自引:0,他引:10
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A G Bodnar J M Cooper I J Holt J V Leonard A H Schapira 《American journal of human genetics》1993,53(3):663-669
We have studied cultured skin fibroblasts from a patient with a fatal mitochondrial disease manifesting soon after birth. These fibroblasts were found to grow only in the presence of pyruvate and uridine, a characteristic of cells lacking mtDNA (rho0 cells). Southern blot and PCR analyses confirmed that the patient's fibroblasts contained less than 2% of control levels of mtDNA. Biochemical analyses indicated that the activities of all the respiratory-chain enzymes were severely decreased in mitochondria isolated from these fibroblasts. In order to elucidate the underlying molecular defect, cell fusions were performed between enucleated fibroblasts from this patient and a human-derived rho0 cell line (rho0 A549.B2). The resulting cybrids were plated in medium lacking pyruvate and uridine, to select for the restoration of respiratory-chain function. Complementation was observed between the nuclear genome of the rho0 A549.B2 cells and the mtDNA of the patient's cells, restoring mtDNA levels and respiratory-chain function in the cybrid cells. These results indicate that mtDNA depletion in our patient is under the control of the nuclear genome. 相似文献
84.
Effect of nucleotide analogs on the cleavage of DNA by the restriction enzymes AluI, DdeI, HinfI, RsaI, and TaqI 总被引:21,自引:0,他引:21
J W Bodnar W Zempsky D Warder C Bergson D C Ward 《The Journal of biological chemistry》1983,258(24):15206-15213
The cleavage of specific DNA sequences by the restriction endonucleases AluI, DdeI, HinfI, RsaI, and TaqI has been studied by monitoring the effect of various nucleotide modifications on the rate of DNA digestion. Bacteriophage fd DNA was completely substituted in one strand with a single nucleotide analog, using an in vitro primed DNA synthesis reaction on a single-stranded viral DNA template. Twelve deoxynucleotide analogs were incorporated into these DNA substrates: 2-aminopurine, 2,6-diaminopurine, deoxytubercidin, deoxyuridine, 5-bromodeoxyuridine, 5-allylamine deoxyuridine, 5-biotinyl deoxyuridine, deoxypseudouridine, deoxyinosine, 8-azadeoxyguanosine, 5-iododeoxycytidine, and 5-bromodeoxycytidine. The restriction enzymes tested varied considerably in their ability to digest hemi-substituted DNAs containing these modified nucleotides. Structural alterations in the base pairs immediately adjacent to the phosphodiester bonds cleaved by the enzyme reduced the rate of enzyme activity most dramatically, and in most cases more than a single determinant on each base pair altered activity. Interactions with nucleotides outside the recognition site seem to have little importance in the binding or catalytic activity of these enzymes. 相似文献
85.
Ia Ia Bodnar 《Arkhiv anatomii, gistologii i émbriologii》1990,98(5):50-55
By means of water deprivation primary- and secondary-compensated and decompensated degrees of dehydration have been caused in 24 rats. Electron microscopical investigation has demonstrated a more pronounced granularity of cardiomyocytes in the left than in the right cardiac auricles. During the alimentary dehydration granularity of the atrial cardiomyocytes in the right auricles increases at the primary- and secondary-compensated degrees of dehydration, in the stage of decompensated dehydration it decreases, the character of distribution of the secretory granules, however, shows certain processes of exhaustion. Granularity of the atrial cardiomyocytes in the left auricles during alimentary dehydration of the organism does not change. Changes of the endocrine apparatus in the atrial cardiomyocytes occur against the background of microcirculatory disturbances in both auricles of the heart and are combined with dystrophic changes in cardiomyocytes. 相似文献
86.
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89.
Deibel MR Bodnar AL Yem AW Wolfe CL Heckaman CL Bohanon MJ Mathews WR Sweeney MT Zurenko GE Marotti KR Boyle TP Thorarensen A 《Bioconjugate chemistry》2004,15(2):333-343
Screening of our compound collection identified PNU-92560, a 2-[1,3,4]thiadiazolo[3,2-a]pyrimidine-6-carboxamide, as a novel antibacterial agent. Extensive analogue development identified that the 2-position of the thiadiazole could be functionalized with a linker that would allow the compound to be attached to a solid support. The extreme insolubility of the analogues prevented the mechanism of action for these compounds to be determined utilizing traditional methodology. The solid-supported compounds were utilized as affinity columns to identify elongation factor Tu (EF-Tu) as a putative target for this class of compounds. The activity of the compounds in a metabolic labeling experiments and in translation assay supports the identity of the target for these compounds to be EF-Tu. 相似文献
90.
Epidermal growth factor activates m-calpain (calpain II), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation
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Glading A Bodnar RJ Reynolds IJ Shiraha H Satish L Potter DA Blair HC Wells A 《Molecular and cellular biology》2004,24(6):2499-2512
How m-calpain is activated in cells has challenged investigators because in vitro activation requires near-millimolar calcium. Previously, we demonstrated that m-calpain activation by growth factors requires extracellular signal-regulated kinase (ERK); this enables tail deadhesion and allows productive motility. We now show that ERK directly phosphorylates and activates m-calpain both in vitro and in vivo. We identified serine 50 as required for epidermal growth factor (EGF)-induced calpain activation in vitro and in vivo. Replacing the serine with alanine limits activation by EGF and subsequent cell deadhesion and motility. A construct with the serine converted to glutamic acid displays constitutive activity in vivo; expression of an estrogen receptor fusion construct produces a tamoxifen-sensitive enzyme. Interestingly, EGF-induced m-calpain activation occurs in the absence of increased intracellular calcium levels; EGF triggers calpain even in the presence of intracellular calcium chelators and in calcium-free media. These data provide evidence that m-calpain can be activated through the ERK cascade via direct phosphorylation and that this activation may occur in the absence of cytosolic calcium fluxes. 相似文献