scholarly journals Genome sequence of a diabetes-prone rodent reveals a mutation hotspot around the ParaHox gene cluster

2017 ◽  
Vol 114 (29) ◽  
pp. 7677-7682 ◽  
Author(s):  
Adam D. Hargreaves ◽  
Long Zhou ◽  
Josef Christensen ◽  
Ferdinand Marlétaz ◽  
Shiping Liu ◽  
...  
Keyword(s):  
North Africa ◽  
Type Ii Diabetes ◽  
Chromosomal Region ◽  
Caloric Intake ◽  
Homeobox Gene ◽  
Genomic Region ◽  
Sand Rat ◽  
Parahox Gene ◽  
Parahox Cluster ◽  
Rat Genome

The sand rat Psammomys obesus is a gerbil species native to deserts of North Africa and the Middle East, and is constrained in its ecology because high carbohydrate diets induce obesity and type II diabetes that, in extreme cases, can lead to pancreatic failure and death. We report the sequencing of the sand rat genome and discovery of an unusual, extensive, and mutationally biased GC-rich genomic domain. This highly divergent genomic region encompasses several functionally essential genes, and spans the ParaHox cluster which includes the insulin-regulating homeobox gene Pdx1. The sequence of sand rat Pdx1 has been grossly affected by GC-biased mutation, leading to the highest divergence observed for this gene across the Bilateria. In addition to genomic insights into restricted caloric intake in a desert species, the discovery of a localized chromosomal region subject to elevated mutation suggests that mutational heterogeneity within genomes could influence the course of evolution.

scholarly journals Genome sequence of a diabetes-prone desert rodent reveals a mutation hotspot around the ParaHox gene cluster

2016 ◽  
Author(s):  
Adam D Hargreaves ◽  
Long Zhou ◽  
Josef Christensen ◽  
Ferdinand Marlétaz ◽  
Shiping Liu ◽  
...  
Keyword(s):  
North Africa ◽  
Type Ii Diabetes ◽  
Caloric Intake ◽  
Homeobox Gene ◽  
Sand Rat ◽  
Diabetes Susceptibility ◽  
Parahox Gene ◽  
Desert Rodent ◽  
Develop Type ◽  
Rat Genome

The sand rat Psammomys obesus is a gerbil native to deserts of North Africa and the Middle East1. Sand rats survive with low caloric intake and when given high carbohydrate diets can become obese and develop type II diabetes2 which, in extreme cases, leads to pancreatic failure and death3,4. Previous studies have reported inability to detect the Pdx1 gene or protein in gerbils5–7, suggesting that absence of this key insulin-regulating homeobox gene might underlie diabetes susceptibility. Here we report sequencing of the sand rat genome and discovery of an extensive, mutationally-biased GC-rich genomic domain encompassing many essential genes, including the elusive Pdx1. The sequence of Pdx1 has been grossly affected by GC-biased mutation leading to the highest divergence observed in the animal kingdom. In addition to molecular insights into restricted caloric intake in a desert species, the discovery that specific chromosomal regions can be subject to elevated mutation rate has widespread significance to evolution.

scholarly journals Comparative Phylogenomic Synteny Network Analysis of Mammalian and Angiosperm Genomes

2018 ◽  
Author(s):  
Tao Zhao ◽  
M. Eric Schranz
Keyword(s):  
Large Scale ◽  
Homeobox Gene ◽  
Gene Families ◽  
Gene Clusters ◽  
Parahox Gene ◽  
Family Networks ◽  
Plant Genomes ◽  
Eukaryotic Gene ◽  
Syntenic Gene ◽  
Phylogenetic Profiling

AbstractBackgroundSynteny analysis is a valuable approach for understanding eukaryotic gene and genome evolution, but still relies largely on pairwise or reference-based comparisons. Network approaches can be utilized to expand large-scale phylogenomic microsynteny studies. There is now a wealth of completed mammalian (animal) and angiosperm (plant) genomes, two very important lineages that have evolved and radiated over the last ~170 million years. Genomic organization and conservation differs greatly between these two groups; however, a systematic and comparative characterization of synteny between the two lineages using the same approaches and metrics has not been undertaken.ResultsWe have built complete microsynteny networks for 87 mammalian and 107 angiosperm genomes, which contain 1,464,753 nodes (genes) and 49,426,268 edges (syntenic connections between genes) for mammals, and 2,234,461 nodes and 46,938,272 edges for angiosperms, respectively. Exploiting network statistics, we present the functional characteristics of extremely conserved and diversified gene families. We summarize the features of all syntenic gene clusters and present lineage-wide phylogenetic profiling, revealing intriguing sub-clade lineage-specific clusters. We depict several representative clusters of important developmental genes in humans, such as CENPJ, p53 and NFE2. Finally, we present the complete homeobox gene family networks for both mammals (including Hox and ParaHox gene clusters) and angiosperms.ConclusionsOur results illustrate and quantify overall synteny conservation and diversification properties of all annotated genes for mammals and angiosperms and show that plant genomes are in general more dynamic.

Do cnidarians have a ParaHox cluster? Analysis of synteny around a Nematostella homeobox gene cluster

2008 ◽  
Vol 10 (6) ◽  
pp. 725-730 ◽  
Author(s):  
Jerome H. L. Hui ◽  
Peter W. H. Holland ◽  
David E. K. Ferrier
Keyword(s):  
Cluster Analysis ◽  
Gene Cluster ◽  
Homeobox Gene ◽  
Parahox Cluster

Experimental diabetes mellitus induced by diet in the sand rat

1965 ◽  
Vol 208 (2) ◽  
pp. 297-300 ◽  
Author(s):  
Howard Haines ◽  
D. B. Hackel ◽  
Knut Schmidt-Nielsen
Keyword(s):  
Diabetes Mellitus ◽  
North Africa ◽  
Experimental Diabetes ◽  
Natural Habitat ◽  
Experimental Diabetes Mellitus ◽  
Sand Rat ◽  
Severe Diabetes ◽  
Fresh Vegetables ◽  
Body Weights ◽  
Purina Laboratory

The sand rat ( Psammomys obesus), a rodent from the Near East and North Africa, becomes diabetic when raised on standard laboratory feeds. Animals collected in their natural habitat, on the other hand, show no signs of diabetes mellitus. Twelve animals were raised in the laboratory on Purina laboratory chow supplemented with fresh vegetables. Most of these animals developed severe diabetes mellitus as indicated by hyperglycemia, glucosuria, and pathological lesions including cataracts, obesity, and ß-cell degranulation and vacuolization of the pancreatic islet tissue. Ten animals raised entirely on fresh vegetables remained healthy with no signs of diabetes. Plasma and urine glucose concentrations, body weights, and the occurrence of cataracts are reported.

Early evolution of a homeobox gene: the parahox gene Gsx in the Cnidaria and the Bilateria

2003 ◽  
Vol 5 (4) ◽  
pp. 331-345 ◽  
Author(s):  
John R. Finnerty ◽  
David Paulson ◽  
Pat Burton ◽  
Kevin Pang ◽  
Mark Q. Martindale
Keyword(s):  
Homeobox Gene ◽  
Early Evolution ◽  
Parahox Gene

scholarly journals Severe head dysgenesis resulting from imbalance between anterior and posterior ontogenetic programs

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Emmanuelle Grall ◽  
Victor Gourain ◽  
Asmaa Naïr ◽  
Elisabeth Martin ◽  
Marie-Christine Birling ◽  
...  
Keyword(s):  
Neural Crest ◽  
Human Development ◽  
Chromosomal Region ◽  
Homeobox Gene ◽  
Neural Crest Cells ◽  
Fetal Demise ◽  
Craniofacial Malformation ◽  
Possible Cause

Abstract Head dysgenesis is a major cause of fetal demise and craniofacial malformation. Although mutations in genes of the head ontogenetic program have been reported, many cases remain unexplained. Head dysgenesis has also been related to trisomy or amplification of the chromosomal region overlapping the CDX2 homeobox gene, a master element of the trunk ontogenetic program. Hence, we investigated the repercussion on head morphogenesis of the imbalance between the head and trunk ontogenetic programs, by means of ectopic rostral expression of CDX2 at gastrulation. This caused severe malformations affecting the forebrain and optic structures, and also the frontonasal process associated with defects in neural crest cells colonization. These malformations are the result of the downregulation of genes of the head program together with the abnormal induction of trunk program genes. Together, these data indicate that the imbalance between the anterior and posterior ontogenetic programs in embryos is a new possible cause of head dysgenesis during human development, linked to defects in setting up anterior neuroectodermal structures.

scholarly journals Lampreys, the jawless vertebrates, contain only two ParaHox gene clusters

2017 ◽  
Vol 114 (34) ◽  
pp. 9146-9151 ◽  
Author(s):  
Huixian Zhang ◽  
Vydianathan Ravi ◽  
Boon-Hui Tay ◽  
Sumanty Tohari ◽  
Nisha E. Pillai ◽  
...  
Keyword(s):  
Hox Genes ◽  
Genome Duplication ◽  
Gene Families ◽  
Gene Clusters ◽  
Insulin Production ◽  
Parahox Gene ◽  
Origin And Evolution ◽  
Parahox Cluster ◽  
The Brain ◽  
Single Cluster

ParaHox genes (Gsx, Pdx, and Cdx) are an ancient family of developmental genes closely related to the Hox genes. They play critical roles in the patterning of brain and gut. The basal chordate, amphioxus, contains a single ParaHox cluster comprising one member of each family, whereas nonteleost jawed vertebrates contain four ParaHox genomic loci with six or seven ParaHox genes. Teleosts, which have experienced an additional whole-genome duplication, contain six ParaHox genomic loci with six ParaHox genes. Jawless vertebrates, represented by lampreys and hagfish, are the most ancient group of vertebrates and are crucial for understanding the origin and evolution of vertebrate gene families. We have previously shown that lampreys contain six Hox gene loci. Here we report that lampreys contain only two ParaHox gene clusters (designated as α- and β-clusters) bearing five ParaHox genes (Gsxα, Pdxα, Cdxα, Gsxβ, and Cdxβ). The order and orientation of the three genes in the α-cluster are identical to that of the single cluster in amphioxus. However, the orientation of Gsxβ in the β-cluster is inverted. Interestingly, Gsxβ is expressed in the eye, unlike its homologs in jawed vertebrates, which are expressed mainly in the brain. The lamprey Pdxα is expressed in the pancreas similar to jawed vertebrate Pdx genes, indicating that the pancreatic expression of Pdx was acquired before the divergence of jawless and jawed vertebrate lineages. It is likely that the lamprey Pdxα plays a crucial role in pancreas specification and insulin production similar to the Pdx of jawed vertebrates.

Morphometric analysis of peroxisomes in hepatocytes of alcohol-fed rats

1989 ◽  
Vol 47 ◽  
pp. 1100-1101
Author(s):  
D.C. Dominguez ◽  
J.T. Ellzey
Keyword(s):  
Caloric Intake ◽  
Volume Density ◽  
Controlled Study ◽  
Control Group ◽  
Numerical Density ◽  
Cacodylate Buffer ◽  
Paired Control ◽  
Experimental Group ◽  
Liver Peroxisomes ◽  
Single Lesion

Peroxisomes which participate in 1ipid metabolism have been shown to be altered in several metabolic disorders and toxic conditions. In alcoholic liver disease, the single lesion most frequently found is lipid accumu1ation in hepatocytes. However, the mechanisms for this 1ipid accumu1ation are not clear. The occurrence of modifications of liver peroxisomes due to excess alcohol consumption has not been subjected to a controlled study. We utilized a combination of cytochemica1 and morphometrictechniques to study the size and number of liver peroxisomes in rats fed an alcohol-supplemented diet compared to those of matched-paired control animals.Male Sprague-Daw1ey rats (400-500 g) received a liquid diet. The experimental group (N = 5/group) was fed a diet containing 30% ethanol-derived calories (EDC) and the control group was fed an isocaloric diet to 30% EDC. A pair feeding procedure was employed to control for caloric intake. Small pieces of liver randomly selected, were fixed in 2.3% -glutaraldehyde in 0.1 M sodium cacodylate buffer, pH 7.2, incubated in a DAB medium and postfixed with. 2% aqueous osmium tetroxide. EM photographs were taken from sections of 3 tissue blocks from each sample (7,200X) with a Zeiss EM10-A (60 kV). With the use of a point counting method and a digital planimeter the volume density (Vv) and numerical density (Nv) were determined.

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