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121.
Genomic organization of the glyceraldehyde-3-phosphate dehydrogenase gene family of Caenorhabditis elegans 总被引:7,自引:0,他引:7
X Y Huang L A Barrios P Vonkhorporn S Honda D G Albertson R M Hecht 《Journal of molecular biology》1989,206(3):411-424
Glyceraldehyde-3-phosphate dehydrogenase (GAPDHase) is encoded by four genes designated gpd-1 through gpd-4 in the nematode Caenorhabditis elegans. gpd-1 has been isolated and sequenced, and is shown here to have a nearly identical copy (gpd-4) with respect to coding and regulatory flanking sequence information as well as to the placement of its two introns. Both genes, which are separated by 250,000 to 300,000 base-pairs were assigned to chromosome II by in situ hybridization and physically linked to a DNA polymorphism located near unc-4 on the genetic map. The genes gpd-2 and gpd-3 are also nearly identical with each other but differ from the gpd-1 and gpd-4 pair with respect to the positions of their two introns and a cluster of amino acid changes within the amino-terminal region of the enzyme. Furthermore, one gene from each pair (gpd-4 and gpd-2) exhibits a single amino acid substitution at positions heretofore known to be conserved in all other systems so far examined including the extreme thermophiles. gpd-2 and gpd-3 are organized as a direct tandem repeat separated by only 244 base-pairs. They have been assigned to an 85,200 base-pair contig that maps to the left end of the X chromosome. The absence of gpd-3 from C. elegans var. Bergerac was used as a marker to map the gpd-2,3 gene pair near unc-20. Northern analyses have shown that gpd-1 and gpd-4 are preferentially expressed in embryos, while the expression of gpd-2 and gpd-3 increases during postembryonic development. These analyses indicate that the gpd-1,4 gene pair encodes the minor isoenzyme, GAPDHase-1, present in all cells of the nematode while the other gene pair (gpd-2,3) encodes the major isoenzyme, GAPDHase-2, preferentially expressed in the bodywall muscle. The G + T-rich and T-rich regions essential for vertebrate beta-globin polyadenylation were also observed for gpd-3. 相似文献
122.
Covariation among discrete phenotypes can arise due to selection for shared functions, and/or shared genetic and developmental underpinnings. The consequences of such phenotypic integration are far-reaching and can act to either facilitate or limit morphological variation. The vertebrate brain is known to act as an “organizer” of craniofacial development, secreting morphogens that can affect the shape of the growing neurocranium, consistent with roles for pleiotropy in brain–neurocranium covariation. Here, we test this hypothesis in cichlid fishes by first examining the degree of shape integration between the brain and the neurocranium using three-dimensional geometric morphometrics in an F5 hybrid population, and then genetically mapping trait covariation using quantitative trait loci (QTL) analysis. We observe shape associations between the brain and the neurocranium, a pattern that holds even when we assess associations between the brain and constituent parts of the neurocranium: the rostrum and braincase. We also recover robust genetic signals for both hard- and soft-tissue traits and identify a genomic region where QTL for the brain and braincase overlap, implicating a role for pleiotropy in patterning trait covariation. Fine mapping of the overlapping genomic region identifies a candidate gene, notch1a, which is known to be involved in patterning skeletal and neural tissues during development. Taken together, these data offer a genetic hypothesis for brain–neurocranium covariation, as well as a potential mechanism by which behavioral shifts may simultaneously drive rapid change in neuroanatomy and craniofacial morphology. 相似文献
123.
East African cichlids exhibit an extraordinary level of morphological diversity. Key to their success has been a dramatic radiation in trophic biology, which has occurred rapidly and repeatedly in different lakes. In this report we take the first step in understanding the genetic basis of differences in cichlid oral jaw design. We estimate the effective number of genetic factors that control differences in the cichlid head through a comprehensive morphological assessment of two Lake Malawi cichlid species and their F(1) and F(2) hybrid progeny. We estimate that between one and 11 factors underlie shape difference of individual bony elements. We show that many of the skeletal differences in the head and oral jaw apparatus are inherited together, suggesting a degree of pleiotropy in the genetic architecture of this character complex. Moreover, we find that cosegregation of shape differences in different elements corresponds to developmental, rather than functional, units. 相似文献
124.
Altizer AM Stewart SG Albertson BK Borgens RB 《The Journal of experimental zoology》2002,293(5):467-477
For over two decades, we have been investigating a strong (ca. 20-100 microA/cm2), outwardly directed electric current driven through the limb stump for the first few days following amputation in regenerating salamanders. This current is driven through the stump in a proximal/distal direction by the amiloride-sensitive transcutaneous voltage of the intact skin of the stump. Limb regeneration can be manipulated by several technique that manipulate this physiology, demonstrating that the ionic current is necessary, but not sufficient, for normal regeneration of the amphibian limb. Here, we demonstrate that a full thickness graft of skin covering the forelimb stump of newts strikingly inhibits the regeneration of the limb, and that this procedure is also highly correlated to a suppression of peak outwardly directed stump currents in those animals that fail to regenerate. 相似文献
125.
Laterality is fundamental to the vertebrate body plan. Here, we investigate the roles of fgf8 signaling in LR patterning of the zebrafish embryo. We find that fgf8 is required for proper asymmetric development of the brain, heart and gut. When fgf8 is absent, nodal signaling is randomized in the lateral plate mesoderm, leading to aberrant LR orientation of the brain and visceral organs. We also show that fgf8 is necessary for proper symmetric development of the pharyngeal skeleton. Attenuated fgf8 signaling results in consistently biased LR asymmetric development of the pharyngeal arches and craniofacial skeleton. Approximately 1/3 of zebrafish ace/fgf8 mutants are missing Kupffer's vesicle (KV), a ciliated structure similar to Hensen's node. We correlate fgf8 deficient laterality defects in the brain and viscera with the absence of KV, supporting a role for KV in proper LR patterning of these structures. Strikingly, we also correlate asymmetric craniofacial development in ace/fgf8 mutants with the presence of KV, suggesting roles for KV in lateralization of the pharyngeal skeleton when fgf8 is absent. These data provide new insights into vertebrate laterality and offer the zebrafish ace/fgf8 mutant as a novel molecular tool to investigate tissue-specific molecular laterality mechanisms. 相似文献
126.
pRb inactivation in mammary cells reveals common mechanisms for tumor initiation and progression in divergent epithelia 总被引:1,自引:0,他引:1 下载免费PDF全文
Retinoblastoma 1 (pRb) and the related pocket proteins, retinoblastoma-like 1 (p107) and retinoblastoma-like 2 (p130) (pRbf, collectively), play a pivotal role in regulating eukaryotic cell cycle progression, apoptosis, and terminal differentiation. While aberrations in the pRb-signaling pathway are common in human cancers, the consequence of pRbf loss in the mammary gland has not been directly assayed in vivo. We reported previously that inactivating these critical cell cycle regulators in divergent cell types, either brain epithelium or astrocytes, abrogates the cell cycle restriction point, leading to increased cell proliferation and apoptosis, and predisposing to cancer. Here we report that mouse mammary epithelium is similar in its requirements for pRbf function; Rbf inactivation by T121, a fragment of SV40 T antigen that binds to and inactivates pRbf proteins, increases proliferation and apoptosis. Mammary adenocarcinomas form within 16 mo. Most apoptosis is regulated by p53, which has no impact on proliferation, and heterozygosity for a p53 null allele significantly shortens tumor latency. Most tumors in p53 heterozygous mice undergo loss of the wild-type p53 allele. We show that the mechanism of p53 loss of heterozygosity is not simply the consequence of Chromosome 11 aneuploidy and further that chromosomal instability subsequent to p53 loss is minimal. The mechanisms for pRb and p53 tumor suppression in the epithelia of two distinct tissues, mammary gland and brain, are indistinguishable. Further, this study has produced a highly penetrant breast cancer model based on aberrations commonly observed in the human disease. 相似文献
127.
The potential role of swift foxes (Vulpes velox) and their fleas in plague outbreaks in prairie dogs 总被引:1,自引:0,他引:1
Salkeld DJ Eisen RJ Stapp P Wilder AP Lowell J Tripp DW Albertson D Antolin MF 《Journal of wildlife diseases》2007,43(3):425-431
Swift foxes (Vulpes velox) have been proposed as potential carriers of fleas infected with the bacterium Yersinia pestis between areas of epizootics in black-tailed prairie dogs (Cynomys ludovicianus). We examined antibody prevalence rates of a population of swift foxes in Colorado, USA, and used polymerase chain reaction (PCR) assays to examine their flea biota for evidence of Y. pestis. Fifteen of 61 (24%) captured foxes were seropositive, and antibody prevalence was spatially correlated with epizootic plague activity in prairie dog colonies in the year of, and previous to, the study. Foxes commonly harbored the flea Pulex simulans, though none of the fleas was positive for Y. pestis. 相似文献
128.
Kiranjit K. Dhillon Julia M. Sidorova Tina M. Albertson Judith B. Anderson Warren C. Ladiges Peter S. Rabinovitch Bradley D. Preston Raymond J. Monnat 《DNA Repair》2010,9(1):11-22
Werner syndrome (WS) is a human autosomal recessive genetic instability and cancer predisposition syndrome with features of premature aging. Several genetically determined mouse models of WS have been generated, however, none develops features of premature aging or an elevated risk of neoplasia unless additional genetic perturbations are introduced. In order to determine whether differences in cellular phenotype could explain the discrepant phenotypes of Wrn?/? mice and WRN-deficient humans, we compared the cellular phenotype of newly derived Wrn?/? mouse primary fibroblasts with previous analyses of primary and transformed fibroblasts from WS patients and with newly derived, WRN-depleted human primary fibroblasts. These analyses confirmed previously reported cellular phenotypes of WRN-mutant and WRN-deficient human fibroblasts, and demonstrated that the human WRN-deficient cellular phenotype can be detected in cells grown in 5% or in 20% oxygen. In contrast, we did not identify prominent cellular phenotypes present in WRN-deficient human cells in Wrn?/? mouse fibroblasts. Our results indicate that human and mouse fibroblasts have different functional requirements for WRN protein, and that the absence of a strong cellular phenotype may in part explain the failure of Wrn?/? mice to develop an organismal phenotype resembling Werner syndrome. 相似文献
129.
Cichlids have undergone extensive evolutionary modifications of their feeding apparatus, making them an ideal model to study the factors that underlie craniofacial diversity. Recent studies have provided critical insights into the molecular mechanisms that have contributed to the origin and maintenance of cichlid trophic diversity. We review this body of work, which shows that the cichlid jaw is regulated by a few genes of major additive effect, and is composed of modules that have evolved under strong divergent selection. Adaptive variation in cichlid jaw shape is evident early in development and is associated with allelic variation in and expression of bmp4. Modulating this growth factor in the experimentally tractable zebrafish model reproduces natural variation in cichlid jaw shape, supporting a role for bmp4 in craniofacial evolution. These data demonstrate the utility of the cichlid jaw as a model for studying the genetic and developmental basis of evolutionary changes in craniofacial morphology. 相似文献
130.
G. Renee Albertson Robin W. Baird Marc Oremus M. Micahel Poole Karen K. Martien C. Scott Baker 《Conservation Genetics》2017,18(1):33-51
Rough-toothed dolphins have a worldwide tropical and subtropical distribution, yet little is known about the population structure and social organization of this typically open-ocean species. Although it has been assumed that pelagic dolphins range widely due to the lack of apparent barriers and unpredictable prey distribution, recent evidence suggests rough-toothed dolphins exhibit fidelity to some oceanic islands. Using the most comprehensively extensive dataset for this species to date, we assess the isolation and interchange of rough-toothed dolphins at the regional and oceanic scale within the central Pacific Ocean. Using mtDNA and microsatellite genotyping (nDNA), we analyzed samples of insular communities from the main Hawaiian (Kaua‘i n = 93, O‘ahu n = 9, Hawai‘i n = 57), French Polynesian (n = 70) and Samoan (n = 16) archipelagos, and pelagic samples off the Northwestern Hawaiian Islands (n = 18). An overall AMOVA indicated strong genetic differentiation among islands (mtDNA FST = 0.265; p < 0.001; nDNA FST = 0.038; p < 0.001), as well as among archipelagos (mtDNA FST = 0.299; p < 0.001; nDNA FST = 0.055; p < 0.001). Shared haplotypes (n = 4) between the archipelagos may be a product of a relatively recent divergence and/or periodic exchange from poorly understood pelagic populations. Analyses using STRUCTURE and GENELAND identified four separate management units among archipelagos and within the Hawaiian Islands. These results confirm the presence of multiple insular populations within the Pacific and island-specific genetic isolation among populations attached to islands in each archipelago. Insular populations seem most prevalent where oceanographic conditions indicate high local productivity or a discontinuity with surrounding oligotrophic areas. Our findings have important implications for a little studied species that faces increasing anthropogenic threats around oceanic islands. 相似文献