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131.
HP1 is an essential heterochromatin-associated protein in Drosophila. HP1 has dosage-dependent effects on the silencing of euchromatic genes that are mislocalized to heterochromatin and is required for the normal expression of at least two heterochromatic genes. HP1 is multiply phosphorylated in vivo, and HP1 hyperphosphorylation is correlated with heterochromatin assembly during development. The purpose of this study was to test whether HP1 phosphorylation modifies biological activity and biochemical properties of HP1. To determine sites of HP1 phosphorylation in vivo and whether phosphorylation affects any biochemical properties of HP1, we expressed Drosophila HP1 in lepidopteran cultured cells using a recombinant baculovirus vector. Phosphopeptides were identified by matrix-assisted laser desorption ionization/time of flight mass spectroscopy; these peptides contain target sites for casein kinase II, protein tyrosine kinase, and PIM-1 kinase. Purified HP1 from bacterial (unphosphorylated) and lepidopteran (phosphorylated) cells has similar secondary structure. Phosphorylation has no effect on HP1 self-association but alters the DNA binding properties of HP1, suggesting that phosphorylation could differentially regulate HP1-dependent interactions. Serine-to-alanine and serine-to-glutamate substitutions at consensus protein kinase motifs resulted in reduction or loss of silencing activity of mutant HP1 in transgenic flies. These results suggest that dynamic phosphorylation/dephosphorylation regulates HP1 activity in heterochromatic silencing. 相似文献
132.
cis-Acting determinants of heterochromatin formation on Drosophila melanogaster chromosome four
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Sun FL Haynes K Simpson CL Lee SD Collins L Wuller J Eissenberg JC Elgin SC 《Molecular and cellular biology》2004,24(18):8210-8220
The heterochromatic domains of Drosophila melanogaster (pericentric heterochromatin, telomeres, and the fourth chromosome) are characterized by histone hypoacetylation, high levels of histone H3 methylated on lysine 9 (H3-mK9), and association with heterochromatin protein 1 (HP1). While the specific interaction of HP1 with both H3-mK9 and histone methyltransferases suggests a mechanism for the maintenance of heterochromatin, it leaves open the question of how heterochromatin formation is targeted to specific domains. Expression characteristics of reporter transgenes inserted at different sites in the fourth chromosome define a minimum of three euchromatic and three heterochromatic domains, interspersed. Here we searched for cis-acting DNA sequence determinants that specify heterochromatic domains. Genetic screens for a switch in phenotype demonstrate that local deletions or duplications of 5 to 80 kb of DNA flanking a transposon reporter can lead to the loss or acquisition of variegation, pointing to short-range cis-acting determinants for silencing. This silencing is dependent on HP1. A switch in transgene expression correlates with a switch in chromatin structure, judged by nuclease accessibility. Mapping data implicate the 1360 transposon as a target for heterochromatin formation. We propose that heterochromatin formation is initiated at dispersed repetitive elements along the fourth chromosome and spreads for approximately 10 kb or until encountering competition from a euchromatic determinant. 相似文献
133.
Statistical methods of DNA sequence analysis: detection of intragenic recombination or gene conversion 总被引:32,自引:4,他引:28
Simple but exact statistical tests for detecting a cluster of associated
nucleotide changes in DNA are presented. The tests are based on the linear
distribution of a set of s sites among a total of n sites, where the s
sites may be the variable sites, sites of insertion/deletion, or
categorized in some other way. These tests are especially useful for
detecting gene conversion and intragenic recombination in a sample of DNA
sequences. In this case, the sites of interest are those that correspond to
particular ways of splitting the sequences into two groups (e.g., sequences
A and D vs. sequences B, C, and E-J). Each such split is termed a
phylogenetic partition. Application of these methods to a well-documented
case of gene conversion in human gamma-globin genes shows that sites
corresponding to two of the three observed partitions are significantly
clustered, whereas application to hominoid mitochondrial DNA
sequences--among which no recombination is expected to occur--shows no
evidence of such clustering. This indicates that clustering of
partition-specific sites is largely due to intragenic recombination or gene
conversion. Alternative hypotheses explaining the observed clustering of
sites, such as biased selection or mutation, are discussed.
相似文献
134.
The nucleotide sequences of the cow epsilon 2 and epsilon 4 globin genes
were determined. The sequences were 95% identical. These genes arose via a
four-gene block duplication that also gave rise to the bovine fetal (gamma)
and adult (beta) genes. Their deduced amino acid sequences are unlike any
previously reported fetal or adult globins; rather, comparison to other
mammalian globin genes indicates that they are embryonic in nature. The
sequence data indicate that these two genes have converted each other
during evolution. Pairwise comparison to the corresponding goat genes shows
greater similarity between paralogues than between more directly related
orthologues. This is in direct contrast to the situation between the cow
and goat fetal and adult genes. These observations suggest that the
frequency of DNA conversion or the fixation of conversion events may vary
in different locations of the cow beta-globin cluster.
相似文献
135.
136.
Human responses to propionic acid. I. Quantification of within- and between-participant variation in perception by normosmics and anosmics 总被引:4,自引:3,他引:1
The objective of this study was to fully characterize normosmic perception
of stimuli expected to cause widely varying degrees of olfactory and nasal
trigeminal stimulation and to directly evaluate the possible role of
olfactory nerve stimulation in nasal irritation sensitivity. During each of
four identical test sessions, four anosmic and 31 normosmic participants
were presented with a range of concentrations extending from peri-threshold
for normosmics to supra- threshold for anosmics. For each session, odor (O)
and nasal irritation (NI) sensitivities were summarized in terms of the
concentrations required to produce four sensation levels ('iso-response'
concentrations). Within-participant variation in these iso-response
concentrations was < 10-fold for 95% of normosmics, for both O and NI.
For O but not NI, these apparent fluctuations in sensitivity were largely
accounted for by the uncertainty surrounding the iso-response
concentrations calculated for each session. Anosmics exhibited minimal
within- and between-participant variation in NI and required, for all but
the highest perceptual level, a higher concentration than almost all
normosmics. Between-participant variation, expressed in terms of 90%
confidence interval widths, was approximately 0.5 log units for both O and
NI for the highest perceptual level, but increased to approximately 0.8 and
1.8 log units, respectively, for the lowest (peri- threshold) level. Our
findings suggest that: (i) most apparent variation over time in O
sensitivity is actually a reflection of the uncertainty surrounding
estimates of sensitivity obtained for each session; (ii) within- and
between-participant variation in O sensitivity is far less than is commonly
reported; and (iii) low to moderate levels of NI in normosmics are the
result of relatively weak trigeminal stimulation combined with much greater
olfactory activation.
相似文献
137.
Regier JC; Fang QQ; Mitter C; Peigler RS; Friedlander TP; Solis MA 《Molecular biology and evolution》1998,15(9):1172-1182
Evolution and phylogenetic utility of the period gene are explored through
sequence analysis of a relatively conserved 909-bp fragment in 26
lepidopteran species. Taxa range from tribes to superfamilies, primarily
within the putative clade Macrolepidotera plus near outgroups, and include
both strongly established and problematic groupings. Their divergence dates
probably range from the late Cretaceous through much of the Tertiary.
Comparisons within the same set of closely related species show that amino
acid substitutions in period occur 4.9 and 44 times as frequently as they
do in two other nuclear genes--dopa decarboxylase and elongation factor-1
alpha, respectively. In contrast, rates of observed synonymous substitution
are within 60% of each other for these three genes. Synonymous changes in
period approach saturation by the family level, whereas nonsynonymous and
amino acid divergences across the Macrolepidoptera are less than half the
maximal values reported for this gene. Phylogenetic analyses of period
strongly supported groupings at the family level and below. In contrast to
previous analyses at this level with other nuclear genes, much of the
information lies in nonsynonymous change. Relationships up to the
superfamily level were recovered with decreasing effectiveness, and little,
if any, signal was apparent regarding relationships among superfamilies.
This could reflect rapid radiation of the superfamilies, however, rather
than saturation in the period locus; thus, period, in combination with
other genes, remains a plausible candidate for approaching the difficult
problems of lepidopteran family and superfamily relationships.
相似文献
138.
Multiple haplotypes from each of three nuclear loci were isolated and
sequenced from geographic populations of the American oyster, Crassostrea
virginica. In tests of alternative phylogeographic hypotheses for this
species, nuclear gene genealogies constructed for these haplotypes were
compared to one another, to a mitochondrial gene tree, and to patterns of
allele frequency variation in nuclear restriction site polymorphisms
(RFLPs) and allozymes. Oyster populations from the Atlantic versus the Gulf
of Mexico are not reciprocally monophyletic in any of the nuclear gene
trees, despite considerable genetic variation and despite large allele
frequency differences previously reported in several other genetic assays.
If these populations were separated vicariantly in the past, either
insufficient time has elapsed for neutral lineage sorting to have achieved
monophyly at most nuclear loci, or balancing selection may have inhibited
lineage extinction, or secondary gene flow may have moved haplotypes
between regions. These and other possibilities are examined in light of
available genetic evidence, and it is concluded that no simple explanation
can account for the great variety of population genetic patterns across
loci displayed by American oysters. Regardless of the source of this
heterogeneity, this study provides an empirical demonstration that
different sequences of DNA within the same organismal pedigree can have
quite different phylogeographic histories.
相似文献
139.
Cytosolic isocitrate dehydrogenase in humans, mice, and voles and phylogenetic analysis of the enzyme family 总被引:3,自引:0,他引:3
Nekrutenko A; Hillis DM; Patton JC; Bradley RD; Baker RJ 《Molecular biology and evolution》1998,15(12):1674-1684
In this study, we report cDNA sequences of the cytosolic NADP-dependent
isocitrate dehydrogenase for humans, mice, and two species of voles
(Microtus mexicanus and Microtus ochrogaster). Inferred amino acid
sequences from these taxa display a high level of amino acid sequence
conservation, comparable to that of myosin beta heavy chain, and share
known structural features. A Caenorhabditis elegans enzyme that was
previously identified as a protein similar to isocitrate dehydrogenase is
most likely the NADP-dependent cytosolic isocitrate dehydrogenase enzyme
equivalent, based on amino acid similarity to mammalian enzymes and
phylogenetic analysis. We also suggest that NADP-dependent isocitrate
dehydrogenases characterized from alfalfa, soybean, and eucalyptus are most
likely cytosolic enzymes. The phylogenetic tree of various isocitrate
dehydrogenases from eukaryotic sources revealed that independent gene
duplications may have given rise to the cytosolic and mitochondrial forms
of NADP-dependent isocitrate dehydrogenase in animals and fungi. There
appears to be no statistical support for a hypothesis that the
mitochondrial and cytosolic forms of the enzyme are orthologous in these
groups. A possible scenario of the evolution of NADP-dependent isocitrate
dehydrogenases is proposed.
相似文献
140.
Beuling EE van Dusschoten D Lens P van den Heuvel JC Van As H Ottengraf SP 《Biotechnology and bioengineering》1998,60(3):283-291
The mobility of water in intact biofilms was measured with pulsed field gradient nuclear magnetic resonance (PFG-NMR) and used to characterise their diffusive properties. The results obtained with several well-defined systems, viz. pure water, agar, and agar containing inert particles or active bacteria were compared to glucose diffusion coefficients measured with micro-electrodes and those calculated utilising theoretical diffusion models. A good correspondence was observed indicating that PFG-NMR should also enable the measurement of diffusion coefficients in heterogeneous biological systems. Diffusion coefficients of several types of natural biofilms were measured as well and these results were related to the physical biofilm characteristics. The values had a high accuracy and reflected the properties of a sample of ca. 100 biofilms, while non-uniformity or non-geometrical shapes did not negatively influence the results. The monitored PFG-NMR signal contains supplementary information on e.g. cell fraction or spatial organisation but quantitative analysis was not yet possible. Copyright 1998 John Wiley & Sons, Inc. 相似文献