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991.
Substantial efforts are focused on identifying single-nucleotide polymorphisms (SNPs) throughout the human genome, particularly in coding regions (cSNPs), for both linkage disequilibrium and association studies. Less attention, however, has been directed to the clarification of evolutionary processes that are responsible for the variability in nucleotide diversity among different regions of the genome. We report here the population sequence diversity of genomic segments within a 450-kb cluster of olfactory receptor (OR) genes on human chromosome 17. We found a dichotomy in the pattern of nucleotide diversity between OR pseudogenes and introns on the one hand and the closely interspersed intact genes on the other. We suggest that weak positive selection is responsible for the observed patterns of genetic variation. This is inferred from a lower ratio of polymorphism to divergence in genes compared with pseudogenes or introns, high non-synonymous substitution rates in OR genes, and a small but significant overall reduction in variability in the entire OR gene cluster compared with other genomic regions. The dichotomy among functionally different segments within a short genomic distance requires high recombination rates within this OR cluster. Our work demonstrates the impact of weak positive selection on human nucleotide diversity, and has implications for the evolution of the olfactory repertoire. 相似文献
992.
The activins (dimers of betaA or betaB subunits, encoded by the genes Inhba and Inhbb, respectively) are TGF-beta superfamily members that have roles in reproduction and development. Whereas mice homozygous for the Inhba-null allele demonstrate disruption of whisker, palate and tooth development, leading to neonatal lethality, homozygous Inhbb-null mice are viable, fertile and have eye defects. To determine if these phenotypes were due to spatiotemporal expression differences of the ligands or disruption of specific ligand-receptor interactions, we replaced the region of Inhba encoding the mature protein with Inhbb, creating the allele Inhbatm2Zuk (hereafter designated InhbaBK). Although the craniofacial phenotypes of the Inhba-null mutation were rescued by the InhbaBK allele, somatic, testicular, genital and hair growth were grossly affected and influenced by the dosage and bioactivity of the allele. Thus, functional compensation within the TGF-beta superfamily can occur if the replacement gene is expressed appropriately. The novel phenotypes in these mice further illustrate the usefulness of insertion strategies for defining protein function. 相似文献
993.
Bishop CE Whitworth DJ Qin Y Agoulnik AI Agoulnik IU Harrison WR Behringer RR Overbeek PA 《Nature genetics》2000,26(4):490-494
In most mammals, male development is triggered by the transient expression of the Y-chromosome gene, Sry, which initiates a cascade of gene interactions ultimately leading to the formation of a testis from the indifferent fetal gonad. Several genes, in particular Sox9, have a crucial role in this pathway. Despite this, the direct downstream targets of Sry and the nature of the pathway itself remain to be clearly established. We report here a new dominant insertional mutation, Odsex (Ods), in which XX mice carrying a 150-kb deletion (approximately 1 Mb upstream of Sox9) develop as sterile XX males lacking Sry. During embryogenesis, wild-type XX fetal gonads downregulate Sox9 expression, whereas XY and XX Ods/+ fetal gonads upregulate and maintain its expression. We propose that Ods has removed a long-range, gonad-specific regulatory element that mediates the repression of Sox9 expression in XX fetal gonads. This repression would normally be antagonized by Sry protein in XY embryos. Our data are consistent with Sox9 being a direct downstream target of Sry and provide genetic evidence to support a general repressor model of sex determination in mammals. 相似文献
994.
Demethylation of the zygotic paternal genome 总被引:56,自引:0,他引:56
995.
Myoglobin-like aerotaxis transducers in Archaea and Bacteria 总被引:14,自引:0,他引:14
Haem-containing proteins such as haemoglobin and myoglobin play an essential role in oxygen transport and storage. Comparison of the amino-acid sequences of globins from Bacteria and Eukarya suggests that they share an early common ancestor, even though the proteins perform different functions in these two kingdoms. Until now, no members of the globin family have been found in the third kingdom, Archaea. Recent studies of biological signalling in the Bacteria and Eukarya have revealed a new class of haem-containing proteins that serve as sensors. Until now, no haem-based sensor has been described in the Archaea. Here we report the first myoglobin-like, haem-containing protein in the Archaea, and the first haem-based aerotactic transducer in the Bacteria (termed HemAT-Hs for the archaeon Halobacterium salinarum, and HemAT-Bs for Bacillus subtilis). These proteins exhibit spectral properties similar to those of myoglobin and trigger aerotactic responses. 相似文献
996.
DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae 总被引:23,自引:0,他引:23
Heidelberg JF Eisen JA Nelson WC Clayton RA Gwinn ML Dodson RJ Haft DH Hickey EK Peterson JD Umayam L Gill SR Nelson KE Read TD Tettelin H Richardson D Ermolaeva MD Vamathevan J Bass S Qin H Dragoi I Sellers P McDonald L Utterback T Fleishmann RD Nierman WC White O Salzberg SL Smith HO Colwell RR Mekalanos JJ Venter JC Fraser CM 《Nature》2000,406(6795):477-483
997.
Although the image of crocodyliforms as 'unchanged living fossils' is naive, several morphological features of the group are thought to have varied only within narrow limits during the course of evolution. These include an elongate snout with an array of conical teeth, a dorsoventrally flattened skull and a posteriorly positioned jaw articulation, which provides a powerful bite force. Here we report an exquisitely preserved specimen of a new taxon from the Late Cretaceous of Madagascar that deviates profoundly from this Bauplan, possessing an extremely blunt snout, a tall, rounded skull, an anteriorly shifted jaw joint and clove-shaped, multicusped teeth reminiscent of those of some ornithischian dinosaurs. This last feature implies that the diet of the new taxon may have been predominantly if not exclusively herbivorous. A close relationship with notosuchid crocodyliforms, particularly Uruguaysuchus (Late Cretaceous, Uruguay) is suggested by several shared derived features; this supports a biogeographical hypothesis that Madagascar and South America were linked during the Late Cretaceous. 相似文献
998.
999.
Identification of genes that modify ataxin-1-induced neurodegeneration 总被引:55,自引:0,他引:55
1000.
Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice 总被引:48,自引:0,他引:48
Cockayne DA Hamilton SG Zhu QM Dunn PM Zhong Y Novakovic S Malmberg AB Cain G Berson A Kassotakis L Hedley L Lachnit WG Burnstock G McMahon SB Ford AP 《Nature》2000,407(6807):1011-1015
Extracellular ATP is implicated in numerous sensory processes ranging from the response to pain to the regulation of motility in visceral organs. The ATP receptor P2X3 is selectively expressed on small diameter sensory neurons, supporting this hypothesis. Here we show that mice deficient in P2X3 lose the rapidly desensitizing ATP-induced currents in dorsal root ganglion neurons. P2X3 deficiency also causes a reduction in the sustained ATP-induced currents in nodose ganglion neurons. P2X3-null mice have reduced pain-related behaviour in response to injection of ATP and formalin. Significantly, P2X3-null mice exhibit a marked urinary bladder hyporeflexia, characterized by decreased voiding frequency and increased bladder capacity, but normal bladder pressures. Immunohistochemical studies localize P2X3 to nerve fibres innervating the urinary bladder of wild-type mice, and show that loss of P2X3 does not alter sensory neuron innervation density. Thus, P2X3 is critical for peripheral pain responses and afferent pathways controlling urinary bladder volume reflexes. Antagonists to P2X3 may therefore have therapeutic potential in the treatment of disorders of urine storage and voiding such as overactive bladder. 相似文献