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51.
52.
Forbidden synonymous substitutions in coding regions 总被引:2,自引:0,他引:2
In the evolution of highly conserved genes, a few "synonymous"
substitutions at third bases that would not alter the protein sequence are
forbidden or very rare, presumably as a result of functional requirements
of the gene or the messenger RNA. Another 10% or 20% of codons are
significantly less variable by synonymous substitution than are the
majority of codons. The changes that occur at the majority of third bases
are subject to codon usage restrictions. These usage restrictions control
sequence similarities between very distant genes. For example, 70% of third
bases are identical in calmodulin genes of man and trypanosome. Third-base
similarities of distant genes for conserved proteins are mathematically
predicted, on the basis of the G+C composition of third bases. These
observations indicate the need for reexamination of methods used to
calculate synonymous substitutions.
相似文献
53.
Human alpha-galactosidase A (alpha-Gal A) is the lysosomal glycohydrolase
that cleaves the terminal alpha-galactosyl moieties of various
glycoconjugates. Overexpression of the enzyme in Chinese hamster ovary
(CHO) cells results in high intracellular enzyme accumulation and the
selective secretion of active enzyme. Structural analysis of the N -linked
oligosaccharides of the intracellular and secreted glycoforms revealed that
the secreted enzyme's oligosaccharides were remarkably heterogeneous,
having high mannose (63%), complex (30%), and hybrid (5%) structures. The
major high mannose oligosaccharides were Man5-7GlcNAc2 species.
Approximately 40% of the high mannose and 30% of the hybrid
oligosaccharides had phosphate monoester groups. The complex
oligosaccharides were mono-, bi- , 2,4-tri-, 2,6-tri- and tetraantennary
with or without core-region fucose, many of which had incomplete outer
chains. Approximately 30% of the complex oligosaccharides were mono- or
disialylated. Sialic acids were mostly N -acetylneuraminic acid and
occurred exclusively in alpha2, 3-linkage. In contrast, the intracellular
enzyme had only small amounts of complex chains (7.7%) and had
predominantly high mannose oligosaccharides (92%), mostly Man5GlcNAc2 and
smaller species, of which only 3% were phosphorylated. The complex
oligosaccharides were fucosylated and had the same antennary structures as
the secreted enzyme. Although most had mature outer chains, none were
sialylated. Thus, the overexpression of human alpha-Gal A in CHO cells
resulted in different oligosaccharide structures on the secreted and
intracellular glycoforms, the highly heterogeneous secreted forms
presumably due to the high level expression and impaired glycosylation in
the trans- Golgi network, and the predominately Man5-7GlcNAc2 cellular
glycoforms resulting from carbohydrate trimming in the lysosome.
相似文献
54.
55.
56.
Evolution of the Sry genes 总被引:4,自引:3,他引:1
Existing DNA sequence data on the Sry gene, the mammalian sex- determining
locus in the Y chromosome, were analyzed for primates, rodents, and bovids.
In all three taxonomic groups, the terminal sequences evolved faster than
the HMG (high mobility group) boxes, and this applies both to synonymous
(Ks) and nonsynonymous (Ka) nucleotide substitutions. Similar intragenic
correlation between synonymous and nonsynonymous substitution rates was not
found either in other mammalian genes that contain a conservative box (Sox,
Msx) or in the MADS-box genes of plants. The rate of nonsynonymous
substitutions exceeds significantly that of synonymous substitutions in the
terminal Sry sequences of apes. We did not find good support for the
hypothesis that the high evolutionary rate of Sry would be associated with
a promiscuous mating system.
相似文献
57.
Ro ribonucleoproteins are composed of Y RNAs and the Ro 60 kDa protein. While the Ro 60 kDa protein is implicated in an RNA discard pathway that recognizes 3'-extended 5S rRNAs, the function of Y RNAs remains unknown [O'Brien,C.A. and Wolin,S.L. (1995) Genes Dev. 8,2891-2903]. Y5 RNA occupies a large fraction of Ro 60 kDa protein in human Ro RNPs, contains an atypical 3'-extension not found on other Y RNAs, and constitutes an RNA antigen in certain autoimmune patients [Boulanger et al. (1995) Clin. Exp. Immunol. 99, 29-36]. An overabundance of Y RNA retroposed pseudogenes has previously complicated the isolation of mammalian Y RNA genes. The source gene for Y5 RNA was isolated from human DNA as well as from Galago senegalis DNA. Authenticity of the hY5 RNA gene was demonstrated in vivo and its activity was compared with the hY4 RNA gene that also uses a type 3 promoter for RNA polymerase III. The hY5 RNA gene was subsequently found to reside within a few hundred thousand base pairs of other Y RNA genes and the linear order of the four human Y RNA genes on chromosome 7q36 was determined. Phylogenetic comparative analyses of promoter and RNA structure indicate that the Y5 RNA gene has been subjected to positive selection during primate evolution. Consistent with the proposal of O'Brien and Harley [O'Brian,C.A. and Wolin,S.L. (1992) Gene 116, 285-289], analysis of flanking sequences suggest that the hY5 RNA gene may have originated as a retroposon. 相似文献
58.
59.
The human tRNAome consists of more than 500 interspersed tRNA genes comprising 51 anticodon families of largely unequal copy number. We examined tRNA gene copy number variation (tgCNV) in six individuals; two kindreds of two parents and a child, using high coverage whole genome sequence data. Such differences may be important because translation of some mRNAs is sensitive to the relative amounts of tRNAs and because tRNA competition determines translational efficiency vs. fidelity and production of native vs. misfolded proteins. We identified several tRNA gene clusters with CNV, which in some cases were part of larger iterations. In addition there was an isolated tRNALysCUU gene that was absent as a homozygous deletion in one of the parents. When assessed by semiquantitative PCR in 98 DNA samples representing a wide variety of ethnicities, this allele was found deleted in hetero- or homozygosity in all groups at ~ 50% frequency. This is the first report of copy number variation of human tRNA genes. We conclude that tgCNV exists at significant levels among individual humans and discuss the results in terms of genetic diversity and prior genome wide association studies (GWAS) that suggest the importance of the ratio of tRNALys isoacceptors in Type-2 diabetes. 相似文献
60.
Christina Theisen Susanne Fuchs-Winkelmann Karola Knappstein Turgay Efe Jan Schmitt Juergen RJ Paletta Markus D Schofer 《Biomedical engineering online》2010,9(1):9