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71.
72.
The early adaptive evolution of calmodulin 总被引:7,自引:0,他引:7
Baba ML; Goodman M; Berger-Cohn J; Demaille JG; Matsuda G 《Molecular biology and evolution》1984,1(6):442-455
Interaction between gene duplication and natural selection in molecular
evolution was investigated utilizing a phylogenetic tree constructed by the
parsimony procedure from amino acid sequences of 50 calmodulin- family
protein members. The 50 sequences, belonging to seven protein lineages
related by gene duplication (calmodulin itself, troponin-C, alkali and
regulatory light chains of myosin, parvalbumin, intestinal calcium-binding
protein, and glial S-100 phenylalanine-rich protein), came from a wide
range of eukaryotic taxa and yielded a denser tree (more branch points
within each lineage) than in earlier studies. Evidence obtained from the
reconstructed pattern of base substitutions and deletions in these
ancestral loci suggests that, during the early history of the family,
selection acted as a transforming force on expressed genes among the
duplicates to encode molecular sites with new or modified functions. In
later stages of descent, however, selection was a conserving force that
preserved the structures of many coadapted functional sites. Each branch of
the family was found to have a unique average tempo of evolutionary change,
apparently regulated through functional constraints. Proteins whose
functions dictate multiple interaction with several other macromolecules
evolved more slowly than those which display fewer protein-protein and
protein-ion interactions, e.g., calmodulin and next troponin-C evolved at
the slowest average rates, whereas parvalbumin evolved at the fastest. The
history of all lineages, however, appears to be characterized by rapid
rates of evolutionary change in earlier periods, followed by slower rates
in more recent periods. A particularly sharp contrast between such fast and
slow rates is found in the evolution of calmodulin, whose rate of change in
earlier eukaryotes was manyfold faster than the average rate over the past
1 billion years. In fact, the amino acid replacements in the nascent
calmodulin lineage occurred at residue positions that in extant metazoans
are largely invariable, lending further support to the Darwinian hypothesis
that natural selection is both a creative and a conserving force in
molecular evolution.
相似文献
73.
Jannine Clapp Daniel J Bolland Jane E Hewitt 《Briefings in Functional Genomics and Prot》2003,2(3):213-223
The genomic basis of facioscapulohumeral muscular dystrophy (FSHD) is of considerable interest because of the unique nature of the molecular mutation, which is a deletion within a large, complex DNA tandem array (D4Z4). This repeat maps within 30 kb of the 4q telomere. Although D4Z4 repeat units each contain an open reading frame that could encode a homeodomain protein, there is no evidence that the repeat is transcribed, and the underlying disease mechanism probably involves a position effect. A recent study has identified a protein complex bound to D4Z4 that contains YY1 and HMGB2, implicating a role for D4Z4 as a repressor. The 4q telomere has two variants, 4qA and 4qB. Although these alleles are present at almost equal frequencies in the general population, FSHD is associated only with the 4qA allele and never with 4qB. This suggests a functional difference between the telomere variants, either in predisposition to deletions within D4Z4 or in the pathological consequence of the deletion. Comparative mapping studies of the FSHD region in primates, mouse and Fugu rubripes have given insights into the evolutionary history of the D4Z4 repeat and of 4qter, although as yet they have not provided any solutions to the FSHD puzzle. 相似文献
74.
Proteolytic enzymes have been used both to modify properties of the cell membrane and to dissociate cells from many tissues including pituitary (4, 5, 12). Exposure of secretory tissues to pronase can alter their secretory response. Thus incubation of pancreatic islets of Langerhans in the presence of low concentrations of pronase increased the subsequent release of insulin in the presence of stimulatory and nonstimulatory glucose concentrations (7). The purpose of the present investigation was to determine whether low concentrations of pronase have the same stimulatory effect on the release of a pituitary hormone, growth hormone. Such an effect on hormone release could be of some importance in view of the development of dissociated cell systems as models for the study of the control of hormone release (4, 5). 相似文献
75.
76.
Selected non-specific plasma esterases in female BALB/c mice, separated by polyacrylamide gel electrophoresis, were qualitatively altered following treatment of the mice with diethylnitrosamine (DEN). These alterations include a decreased preference for naphthyl butyrate as a substrate relative to naphthyl acetate; decreased sensitivity to enhancement by divalent cations such as Ca2+, Mg2+, and Mn2; and an increased sensitivity to inhibition by eserine. All esterase species affected were also quantitatively altered and some were testosterone-dependent. 相似文献
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79.
Langley C Brock C Brouwer G Brown A Clapp L Cohen J Evans T Newman C Orr S Phillips B Rhodes A Webster N Wooldridge K 《Alternatives to laboratory animals : ATLA》2005,33(6):641-648
Sepsis and multiple organ failure are common causes of death in patients admitted to intensive care units. The incidence of sepsis and associated mortalities has been steadily increasing over the past 20 years. Sepsis is a complex inflammatory condition, the precise causes of which are still poorly understood. Animal models of sepsis have the potential to cause substantial suffering, and many of them have been poorly representative of the human syndrome. However, a number of non-animal approaches, including in vitro, in silico and clinical studies, show promise for addressing this situation. This report is based on discussions held at an expert workshop convened by Focus on Alternatives and held in 2004 at the Wellcome Trust, London. It provides an overview of some non-animal approaches to sepsis research, including their strengths and weaknesses, and argues that they should be prioritised for further development. 相似文献
80.
Park SJ Ciccone SL Freie B Kurimasa A Chen DJ Li GC Clapp DW Lee SH 《The Journal of biological chemistry》2004,279(7):6046-6055
Ku70-Ku80 complex is the regulatory subunit of DNA-dependent protein kinase (DNA-PK) and plays an essential role in double-strand break repair following ionizing radiation (IR). It preferentially interacts with chromosomal breaks and protects DNA ends from nuclease attack. Here we show evidence that cells defective in Ku80 exhibit a significantly slow S phase progression following DNA damage. IR-induced retardation in S phase progression in Ku80-/- cells was not due to the lack of DNA-PK kinase activity because both wild-type cells and DNA-PKcs-deficient cells showed no such symptom. Instead, proliferating cell nuclear antigen (PCNA) dissociated from chromosomes following IR in Ku80-deficient cells but not in wild-type or DNA-PKcs-deficient cells. Treatment of HeLa cells with IR induced colocalization of the Ku complex with PCNA on chromosomes. Together, these results suggest that binding of the Ku complex at chromosomal breaks may be necessary to maintain the sliding clamps (PCNA) on chromatin, which would allow cells to resume DNA replication without a major delay following IR. 相似文献