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O Madsen

Publications and source records attributed to O Madsen.

At least 19 recordsLinked to original sources

Resolution of the early placental mammal radiation using Bayesian phylogenetics.

Molecular phylogenetic studies have resolved placental mammals into four major groups, but have not established the full hierarchy of interordinal relationships, including the position of the root. The latter is critical for understanding the early biogeographic history of placentals. We investigated placental phylogeny using Bayesian and maximum-likelihood methods and a 16.4-kilobase molecular data set. Interordinal relationships are almost entirely resolved. The basal split is between Afrotheria and other placentals, at about 103 million years, and may be accounted for by the separation of South America and Africa in the Cretaceous. Crown-group Eutheria may have their most recent common ancestry in the Southern Hemisphere (Gondwana).

Africa↗

Integrated fossil and molecular data reconstruct bat echolocation.

Molecular and morphological data have important roles in illuminating evolutionary history. DNA data often yield well resolved phylogenies for living taxa, but are generally unattainable for fossils. A distinct advantage of morphology is that some types of morphological data may be collected for extinct and extant taxa. Fossils provide a unique window on evolutionary history and may preserve combinations of primitive and derived characters that are not found in extant taxa. Given their unique character complexes, fossils are critical in documenting sequences of character transformation over geologic time and may elucidate otherwise ambiguous patterns of evolution that are not revealed by molecular data alone. Here, we employ a methodological approach that allows for the integration of molecular and paleontological data in deciphering one of the most innovative features in the evolutionary history of mammals-laryngeal echolocation in bats. Molecular data alone, including an expanded data set that includes new sequences for the A2AB gene, suggest that microbats are paraphyletic but do not resolve whether laryngeal echolocation evolved independently in different microbat lineages or evolved in the common ancestor of bats and was subsequently lost in megabats. When scaffolds from molecular phylogenies are incorporated into parsimony analyses of morphological characters, including morphological characters for the Eocene taxa Icaronycteris, Archaeonycteris, Hassianycteris, and Palaeochiropteryx, the resulting trees suggest that laryngeal echolocation evolved in the common ancestor of fossil and extant bats and was subsequently lost in megabats. Molecular dating suggests that crown-group bats last shared a common ancestor 52 to 54 million years ago.

Animals↗

Parallel adaptive radiations in two major clades of placental mammals.

Higher level relationships among placental mammals, as well as the historical biogeography and morphological diversification of this group, remain unclear. Here we analyse independent molecular data sets, having aligned lengths of DNA of 5,708 and 2,947 base pairs, respectively, for all orders of placental mammals. Phylogenetic analyses resolve placental orders into four groups: Xenarthra, Afrotheria, Laurasiatheria, and Euarchonta plus Glires. The first three groups are consistently monophyletic with different methods of analysis. Euarchonta plus Glires is monophyletic or paraphyletic depending on the phylogenetic method. A unique nine-base-pair deletion in exon 11 of the BRCA1 gene provides additional support for the monophyly of Afrotheria, which includes proboscideans, sirenians, hyracoids, tubulidentates, macroscelideans, chrysochlorids and tenrecids. Laurasiatheria contains cetartiodactyls, perissodactyls, carnivores, pangolins, bats and eulipotyphlan insectivores. Parallel adaptive radiations have occurred within Laurasiatheria and Afrotheria. In each group, there are aquatic, ungulate and insectivore-like forms.

Animals↗

Protein sequence signatures support the African clade of mammals.

DNA sequence evidence supports a superordinal clade of mammals that comprises elephants, sea cows, hyraxes, aardvarks, elephant shrews, golden moles, and tenrecs, which all have their origins in Africa, and therefore are dubbed Afrotheria. Morphologically, this appears an unlikely assemblage, which challenges-by including golden moles and tenrecs-the monophyly of the order Lipotyphla (Insectivora). We here identify in three proteins unique combinations of apomorphous amino acid replacements that support this clade. The statistical support for such "sequence signatures" as unambiguous synapomorphic evidence for the naturalness of the Afrotherian clade is reported. Using likelihood, combinatorial, and Bayesian methods we show that the posterior probability of the mammalian tree containing the Afrotherian clade is effectively 1.0, based on conservative assumptions. Presenting sequence data for another African insectivore, the otter shrew Micropotamogale lamottei, we demonstrate that such signatures are diagnostic for including newly investigated species in the Afrotheria. Sequence signatures provide "protein-morphological" synapomorphies that may aid in visualizing monophyletic groupings.

Africa↗

Mitochondrial versus nuclear gene sequences in deep-level mammalian phylogeny reconstruction.

Both mitochondrial and nuclear gene sequences have been employed in efforts to reconstruct deep-level phylogenetic relationships. A fundamental question in molecular systematics concerns the efficacy of different types of sequences in recovering clades at different taxonomic levels. We compared the performance of four mitochondrial data sets (cytochrome b, cytochrome oxidase II, NADH dehydrogenase subunit I, 12S rRNA-tRNA-16S rRNA) and eight nuclear data sets (exonic regions of alpha-2B adrenergic receptor, aquaporin, ss-casein, gamma-fibrinogen, interphotoreceptor retinoid binding protein, kappa-casein, protamine, von Willebrand Factor) in recovering deep-level mammalian clades. We employed parsimony and minimum-evolution with a variety of distance corrections for superimposed substitutions. In 32 different pairwise comparisons between these mitochondrial and nuclear data sets, we used the maximum set of overlapping taxa. In each case, the variable-length bootstrap was used to resample at the size of the smaller data set. The nuclear exons consistently performed better than mitochondrial protein and rRNA-tRNA coding genes on a per-residue basis in recovering benchmark clades. We also concatenated nuclear genes for overlapping taxa and made comparisons with concatenated mitochondrial protein-coding genes from complete mitochondrial genomes. The variable-length bootstrap was used to score the recovery of benchmark clades as a function of the number of resampled base pairs. In every case, the nuclear concatenations were more efficient than the mitochondrial concatenations in recovering benchmark clades. Among genes included in our study, the nuclear genes were much less affected by superimposed substitutions. Nuclear genes having appropriate rates of substitution should receive strong consideration in efforts to reconstruct deep-level phylogenetic relationships.

Animals↗

Hormone coexpression in the adult toad endocrine pancreas: double-label immunofluorescence under basal conditions and after glucose injection.

We have investigated the type and frequency of hormone coexpression in the endocrine pancreas of amphibians both under basal conditions and after sustained glucose loading. Adult male specimens of the wild toad Bufo arenarum were injected with a 50% (w/v) glucose solution (2 g/100 g) for 2 days, while control animals received an equal volume of the vehicle. Serum glucose levels were measured at the time of sacrifice and the pancreatic free lobe was processed for light microscopy. A double-labeling immunofluorescence study was performed for the detection of insulin (I), glucagon (G), somatostatin (S), and pancreatic polypeptide (PP). Heterospecific antisera against the following hormone combinations were used for their detection and immunocytochemical localization: I+G, I+PP, G+PP, S+G, and S+PP; visualization of the reacted IgG's was effected by fluorescein- and rhodamine-conjugated species-specific antibodies as fluorophores. Intracellular hormone coexpression was found to occur in the combinations G+PP, S+G, and S+PP. Moreover, glucose administration caused, together with a marked hyperglycemia (123 +/- 17 vs 23 +/- 1 mg/dl; P < 0.05), a decrease in the fraction of cells containing both G and PP together (from 106.3 +/- 8.1 to 26 +/- 4 cell/mm2) along with a reciprocal rise in the number of cells possessing G alone (from 128.7-152.3 to 235.9-274 cell/mm2). The fewer number of cells coexpressing either of the other two hormone combinations, however, were unaffected by glucose injection. With respect to the simultaneous measurement of I+G and I+PP, no cells were detected with both hormones of either pair, and the I-containing cells were more frequent in each instance in the control toads (264.8 +/- 22.3 to 269.2 +/- 27 cell/mm2). For both combinations, however, this value diminished significantly in the glucose-treated animals (108 +/- 2 cell/mm2 for I+G and 112.1 +/- 7. 8 cell/mm2 for I+PP). While the G-containing cells became more numerous (rising to 235.9 +/- 12.4, 274 +/- 26, and 250.4 +/- 23.7 cell/mm2 for I-G, G-PP, and G-S combinations, respectively), the PP- and S-containing cells remained unaffected. We conclude that the copresence of different hormones within the same cell is a relatively common finding in the non-I-secreting elements of the adult toad pancreas and that the proportions of specific cell types are affected by glucose administration. We thus propose that intracellular hormonal coexpression in this fashion may well represent a rapid and efficient regulatory mechanism for compensating for the metabolic stress imposed by glucose loading.

Animals↗

Molecular evidence for multiple origins of Insectivora and for a new order of endemic African insectivore mammals.

The traditional views regarding the mammalian order Insectivora are that the group descended from a single common ancestor and that it is comprised of the following families: Soricidae (shrews), Tenrecidae (tenrecs), Solenodontidae (solenodons), Talpidae (moles), Erinaceidae (hedgehogs and gymnures), and Chrysochloridae (golden moles). Here we present a molecular analysis that includes representatives of all six families of insectivores, as well as 37 other taxa representing marsupials, monotremes, and all but two orders of placental mammals. These data come from complete sequences of the mitochondrial 12S rRNA, tRNA-Valine, and 16S rRNA genes (2.6 kb). A wide range of different methods of phylogenetic analysis groups the tenrecs and golden moles (both endemic to Africa) in an all-African superordinal clade comprised of elephants, sirenians, hyracoids, aardvark, and elephant shrews, to the exclusion of the other four remaining families of insectivores. Statistical analyses reject the idea of a monophyletic Insectivora as well as traditional concepts of the insectivore suborder Soricomorpha. These findings are supported by sequence analyses of several nuclear genes presented here: vWF, A2AB, and alpha-beta hemoglobin. These results require that the order Insectivora be partitioned and that the two African families (golden moles and tenrecs) be placed in a new order. The African superordinal clade now includes six orders of placental mammals.

Africa↗

Highly congruent molecular support for a diverse superordinal clade of endemic African mammals.

A solution to higher level mammalian phylogeny is going to depend on the congruent establishment of superordinal groupings followed by a linking together of these clades. We present congruent and convincing evidence from four disparate nuclear protein coding genes and from a tandem alignment of the 12S-16S mitochondrial region, for a superordinal clade of endemic African mammals that includes elephant shrews, aardvarks, golden mole, elephants, sirenians, and hyraxes. Because of strong support for golden mole as part of this clade, the Insectivora are rendered paraphyletic or polyphyletic, with constrained monophyly of the insectivores judged significantly worse in the vast majority of tests. Branching arrangement within this clade remains highly uncertain; however, a tandem alignment of the protein coding genes suggests elephant shrew is the earliest African lineage. None of the individual data sets or combinations of data sets support the widely held view of a mirorder Tethytheria (Sirenia/Proboscidea), although only a tandem alignment of protein coding and mitochondrial loci significantly rejects this association. The majority of the data sets and analyses provide strong support for Caviomorpha as part of a monophyletic Rodentia.

Africa↗

Endemic African mammals shake the phylogenetic tree.

The order Insectivora, including living taxa (lipotyphlans) and archaic fossil forms, is central to the question of higher-level relationships among placental mammals. Beginning with Huxley, it has been argued that insectivores retain many primitive features and are closer to the ancestral stock of mammals than are other living groups. Nevertheless, cladistic analysis suggests that living insectivores, at least, are united by derived anatomical features. Here we analyse DNA sequences from three mitochondrial genes and two nuclear genes to examine relationships of insectivores to other mammals. The representative insectivores are not monophyletic in any of our analyses. Rather, golden moles are included in a clade that contains hyraxes, manatees, elephants, elephant shrews and aardvarks. Members of this group are of presumed African origin. This implies that there was an extensive African radiation from a single common ancestor that gave rise to ecologically divergent adaptive types. 12S ribosomal RNA transversions suggest that the base of this radiation occurred during Africa's window of isolation in the Cretaceous period before land connections were developed with Europe in the early Cenozoic era.

Africa↗

Molecular evolution of mammalian aquaporin-2: further evidence that elephant shrew and aardvark join the paenungulate clade.

A 328-bp sequence from exon 1 of the gene for aquaporin-2 (AQP2) was compared in 12 mammalian species, representing as many eutherian orders. This sequence encodes the N-terminal half of this kidney-specific water channel protein. Most amino acid replacements, as well as an insertion, have occurred in extracellular loops connecting the transmembrane helices, in agreement with a lower functional importance of these loops. Phylogenetic analyses were performed with parsimony, distance, and maximum-likelihood methods. The AQP2 data set, alone as well as in combination with previously published alpha A-crystallin protein sequences, strongly supports a clade consisting of elephant, hyrax, aardvark, and elephant shrew, reaching bootstrap values of 99%. This finding fully agrees with the only other presently available sequence data sets that include these taxa, those of von Willebrand factor and interphotoreceptor retinoid-binding protein, and suggests that this extended paenungulate clade is one of the most conspicuous superordinal groupings in eutherian phylogeny. Some support was obtained for an artiodactyl/perissodactyl clade, while the grouping of pholidotes with edentates was contradicted.

Amino Acid Sequence↗

The glucose sensor protein glucokinase is expressed in glucagon-producing alpha-cells.

Expression of glucokinase in hepatocytes and pancreatic 6-cells is of major physiologic importance to mammalian glucose homeostasis. Liver glucokinase catalyzes the first committed step in the disposal of glucose, and beta-cell glucokinase catalyzes a rate-limiting step required for glucose-regulated insulin release. The present study reports the expression of glucokinase in rat glucagon-producing alpha-cells, which are negatively regulated by glucose. Purified rat alpha-cells express glucokinase mRNA and protein with the same transcript length, nucleotide sequence, and immunoreactivity as the beta-cell isoform. Glucokinase activity accounts for more than 50% of glucose phosphorylation in extracts of alpha-cells and for more than 90% of glucose utilization in intact cells. The glucagon-producing tumor MSL-G-AN also contained glucokinase mRNA, protein, and enzymatic activity. These data indicate that glucokinase may serve as a metabolic glucose sensor in pancreatic alpha-cells and, hence, mediate a mechanism for direct regulation of glucagon release by extracellular glucose. Since these cells do not express Glut2, we suggest that glucose sensing does not necessarily require the coexpression of Glut2 and glucokinase.

1-Methyl-3-isobutylxanthine↗

Topographic differences in cell populations and insulin secretion in the endocrine pancreas of the toad Bufo arenarum.

We analyzed the endocrine cell topography within the amphibian pancreas and the relationship of this distribution to lobular variation in insulin content and secretion. Pancreases from adult male toad Bufo arenarum were separated into their five lobes: free, gastric, hepatic, duodenal, and jejunal. Pieces of each lobe were incubated with glucose, arginine, and K+ and the insulin concentration in the medium was measured by radioimmunoassay. In the presence of 2 or 8 mM glucose, 10 mM arginine, and 10 mM K+ the free lobe released a significantly greater amount of insulin than the other lobes, while the output of the gastric lobe was greater than that of the duodenal, hepatic, and jejunal. At 8 mM glucose, every pancreatic lobe released a significantly higher amount of insulin than at 2 mM. The insulin content of the free lobe was significantly higher than that of the others, whereas this parameter was comparable among the latter. These pancreases contained islets of variable size and irregular shape. B and non-B cells, detected by immunoperoxidase staining, were located at the central and peripheral zones of the islets, respectively. A large number of non-B cells were also scattered over the exocrine component. Morphometrical analyses revealed the following sequence of endocrine cell percentage: free lobe > gastric lobe = duodenal lobe > jejunal lobe = hepatic lobe. Some 48% of the endocrine cells were present in the islets, while the remaining 52% were found throughout the exocrine pancreas. In the free lobe, more endocrine cells were located within the islets (65%) than outside and in the gastric lobe the proportion was almost equal (48% within, 52% outside), but in the hepatic, duodenal, and jejunal lobes the majority lay outside the islets (61, 63, and 70% extrainsular, respectively). The area covered by B and D cells was far larger within the islets than outside, with the relative magnitude of this difference being free lobe > gastric lobe > duodenal lobe > hepatic lobe = jejunal lobe. In the free lobe, this relative distribution was more skewed than in the remaining lobes. PP and A cells occupied a more extensive area outside the islets than inside in every lobe. There were no significant differences among the extrainsular areas occupied by each type of endocrine cell within a given pancreatic lobe. These results constitute the first demonstration of the heterogeneity in morphology, insulin content, and secretory function among the pancreatic lobes in B. arenarum. The data further suggest that the nonuniform secretory capacities of amphibian pancreatic lobes reflect localized differences in their insulin content, which heterogeneity in turn stems from the dissimilar distribution and organization of their constituent endocrine-cell populations.

Animals↗

Differential expression of the two nonallelic proinsulin genes in the developing mouse embryo.

In the mouse, insulin is produced from two similar but nonallelic genes that encode proinsulins I and II. We have investigated expression of these two genes during mouse embryonic development, using a PCR to detect the two gene transcripts and immunocytochemistry to visualize the two corresponding proteins. At appearance of the dorsal pancreatic anlage at day 9.5 of gestation, both mRNAs could be detected in the embryos, and both proteins were present together in the same cells of the developing pancreas. At days 9.5 and 10.5, when the ventral anlage appears, there were fewer proinsulin II mRNAs than proinsulin I mRNAs. At day 12.5 this ratio was reversed. Proinsulin II mRNA, but not proinsulin I mRNA, could be detected at day 8.5 in the prepancreatic embryo. Proinsulin II mRNA, but not proinsulin I mRNA, was also found in the heads of embryos at day 9.5 and at all later stages studied. These results indicate that the two proinsulin genes are regulated independently, at least in part. They also suggest that insulin might play a role as a growth factor in the developing mouse brain.

Alleles↗

A soybean coproporphyrinogen oxidase gene is highly expressed in root nodules.

In plants the enzyme coproporphyrinogen oxidase catalyzes the oxidative decarboxylation of coproporphyrinogen III to protoporphyrinogen IX in the heme and chlorophyll biosynthesis pathway(s). We have isolated a soybean coproporphyrinogen oxidase cDNA from a cDNA library and determined the primary structure of the corresponding gene. The coproporphyrinogen oxidase gene encodes a polypeptide with a predicted molecular mass of 43 kDa. The derived amino acid sequence shows 50% similarity to the corresponding yeast amino acid sequence. The main difference is an extension of 67 amino acids at the N-terminus of the soybean polypeptide which may function as a transit peptide. A full-length coproporphyrinogen oxidase cDNA clone complements a yeast mutant deleted of the coproporphyrinogen oxidase gene, thus demonstrating the function of the soybean protein. The soybean coproporphyrinogen oxidase gene is highly expressed in nodules at the stage where several late nodulins including leghemoglobin appear. The coproporphyrinogen oxidase mRNA is also detectable in leaves but at a lower level than in nodules while no mRNA is detectable in roots. The high level of coproporphyrinogen oxidase mRNA in soybean nodules implies that the plant increases heme production in the nodules to meet the demand for additional heme required for hemoprotein formation.

Amino Acid Sequence↗

Presence of islet amyloid polypeptide in rat islet B and D cells determines parallelism and dissociation between rat pancreatic islet amyloid polypeptide and insulin content.

The islet amyloid polypeptide (IAPP) immunoreactivity of the adult rat pancreas is located in insulin-containing B cells as well as in somatostatin-containing D cells. In both cell types, the IAPP immunoreactivity is identical to rat synthetic IAPP in terms of its elution position after reversed phase HPLC and its binding to IAPP antibodies. The IAPP content per 10(6) B-cells is more than 100 fold lower than the corresponding insulin content, but comparable to the IAPP content of D cells. After induction of diabetes by streptozotocin, pancreatic IAPP seems predominantly located in somatostatin-containing cells. In normal rats, pancreatic insulin and IAPP content increase 20 fold from birth to 12 weeks of age; beyond week 12, the further rise in pancreatic insulin was not paralleled by an increase in IAPP content.

Amyloid↗

Detection of proinsulin, C-peptide, insulin-A-chain, and glicentin in pancreatic islet cells of early human fetogenesis.

The presence of C-peptide, proinsulin, insulin-A-chain, and glicentin in human fetal pancreatic cells by using the PAP-technique was investigated and the results obtained compared with the occurrence of insulin or glucagon immunoreactive cells. In pancreatic sections obtained from 10 weeks old human fetuses we could identify cells reacting with antibodies directed against C-peptide, proinsulin, and insulin-A-chain. The majority of the cells were found in the duct epithelium and their number increased from the 10th to 14th week forming clusters near the ducts. The number and localization of the cells correspond exactly to the insulin positive cells. The presence of proinsulin and insulin-A-chains is a further proof of biological activity already in an early step of fetal development. The presence of glicentin-positive cells in the 10th week of gestational age as well as cells reacting with glucagon antibodies provide evidence for active glucagon biosynthesis. The number of these cells increased markedly in the 14th week of gestational age.

Antibodies↗