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Aberrant sex chromosome mechanisms in mammals. Evolutionary aspects.

There are a number of mammalian species with complicated or unknown mechanisms for sex determination. The literature is reviewed with special reference to the origin and evolution of the sex chromosome mechanisms in three species of monotremes and in the following species of rodents: the creeping vole (Microtus oregoni), the mole vole (Ellobius lutescens), the Amami spinous country rat (Tokudaia osimensis), the wood lemming (Myopus schisticolor), the varying lemming (Dicrostonyx torquatus), South American field mice (Akodon sp.), and the short-tailed bandicoot rat (Nesokia indica). Although this is a heterogeneous group with regard to their sex chromosomes, it is striking that among placental mammals only one order, Rodentia, and only two of its subfamilies, Microtinae and Murinae, are represented. Various reasons for this are discussed. Some of these species have proven to be excellent models for studies of fundamental processes involved in sex determination.

Animals↗

The Alsatian tick-borne encephalitis focus: presence of the virus among ticks and small mammals.

An extensive epidemiologic survey was carried out from 1970 to 1974 in order to understand the condition of circulation of tick-borne encephalitis virus between ticks and small mammals in the Alsatian focus, France. The virus has been isolated from Ixodes ricinus adult ticks (30 lots out of 369, representing a total of 5617 ticks), and from Ixodes ricinus nymphs (4 lots out of 251, representing a total of 8587 ticks). The virus has also been isolated from 11 pools of rodent organs (out of 3361 rodents), and HI antibodies were detected in 21 out of 8735 rodent specimens. The virus has never been detected in rodent blood, nor in 10,298 ticks collected engorged from 1505 vertebrate hosts. These results show that Alsatian tick-borne encephalitis focus is stable since the activity of the virus is detected every year, and that the focus is an extended one since the virus is isolated from 5 of 6 study sites, as well as in several control sites.

Animals↗

Evolution of protamine P1 genes in mammals.

Protamine P1 genes have been sequenced following PCR amplification from 11 mammals representing five major mammalian orders: Rodentia (rat and guinea pig), Carnivora (cat and bear), Proboscidea (elephant), Perissodactyla (horse), and Artiodactyla (camel, deer, elk, moose, and gazelle). The predicted amino acid sequence for these genes together with previously reported sequences results in a data set of 25 different P1 genes and 30 different P1 amino acid sequences. The alignment of all these sequences reveals that protamines are amongst the most rapidly diverging proteins studied. In spite of the large number of differences there are conserved motifs that are also common to birds such as the N-terminal ARYR followed by the triple alternating SRSRSR phosphorylation site. The central region contains 3 arginine clusters consisting of 5-6 arginines each. The C-terminus appears to be the most variable region of the protamines. Overall the molecular evolution of P1 genes is in agreement with the expected species evolution supporting that these genes have evolved vertically.

Animals↗

Frequencies of synonymous substitutions in mammals are gene-specific and correlated with frequencies of nonsynonymous substitutions.

The frequencies of synonymous substitutions of mammalian genes cover a much wider range than previously thought. We report here that the different frequencies found in homologous genes from a given mammalian pair are correlated with those in the same homologous genes from a different mammalian pair. This indicates that the frequencies of synonymous substitutions are gene-specific (as are the frequencies of nonsynonymous substitutions), or, in other words, that "fast" and "slow" genes in one mammal are fast and slow, respectively, in any other one. Moreover, the frequencies of synonymous substitutions are correlated with the frequencies of nonsynonymous substitution in the same genes.

Animals↗

Systematic presence of GABA-immunoreactivity in the tubero-infundibular and tubero-hypophyseal dopaminergic axonal systems: an ultrastructural immunogold study on several mammals.

Immunoreactivities for tyrosine hydroxylase (TH), gamma-aminobutyric acid (GABA) and, in some cases, glutamic acid decarboxylase (GAD) were detected by light and electron microscopy in axons projecting into the median eminence and pituitary gland of various mammals (rats, mice, guinea pigs, cats, rabbits and hares). Light microscope immunoperoxidase reactions were performed on adjacent semithin sections of plastic-embedded samples. In the median eminence external zone, the distributions of the TH- and GAD- or GABA-immunoreactive endings were very similar in the anterior and lateral areas, while medially the GABA-labelled endings predominated. Comparable distribution patterns were found in the various species examined. In the pituitary gland, the distributions of GABA- and TH-immunoreactivities were superimposable in the intermediate lobes of all species examined, except in the rabbit and hare in which both types of innervation were lacking. For electron microscopy, the immunogold procedure was applied to sections of lowicryl-embedded samples; simultaneous detection of GABA- and TH-immunoreactivities was enabled by recto-verso double labelling with gold particles of distinct diameters. In the median eminence, GABA-immunoreactivity occurred systematically in the TH-positive endings, while distinct GABA-positive/TH-negative axons were also detected. In the intermediate lobe, the colocalization of TH- and GABA-immunoreactivities was a constant feature of the axons innervating the melanotrophic cells in all the species examined, except in the Leporidae. The functional significance of this colocalization remains to be determined.

Animals↗

The role of mammals in the future of chemical mutagenesis research.

Radiation genetics has demonstrated that mutagenesis is a complex process affected by many factors. The ABCW hypothesis, that mutation frequency per rad over a wide range of organisms, from microbes to man, is linearly related to DNA content, ignores the fact that, within the mouse alone, different cell stages exhibit a range of mutation rates greater than that listed for the whole evolutionary tree. Also ignored are the findings that the important effects of dose rate and some other factors in the mouse were not predictable even from Drosophila. A much greater maze of complexities has already been found in chemical mutagenesis. This is illustrated even by the results obtained from testing of a single drug. Thus, it is clear that the attempt to extend the ABCW hypothesis to chemicals will be of little, if any, predictive value. Similarly, such concepts as the REC (roentgen-equivalent-chemical), designed to express the mutagenic risk from a chemical by a single unit quantitatively related to radiation damage, are defeated by the extreme qualitative differences in response. Unifying theories and simple non-mammalian tests that reliably predict the results in mammals cannot be expected to materialize until much more information has been collected on transmitted mutations induced in mammalian germ cells.

Alkylating Agents↗

The neuroendocrine system in hibernating mammals: present knowledge and open questions.

The present review describes the distribution and the function-dependent reactivity pattern of those peptidergic and aminergic components of the neuroendocrine system of hibernating mammals that have been studied by histological, pharmacological and physiological techniques. Particular attention has been paid to the intrinsic connectivity of the peptidergic apparatus and its input systems. Since the reactivity patterns of the neuroendocrine system show remarkable fluctuations in relation to the various stages of hibernation and euthermia, these fluctuations have been analyzed with respect to (1) their causative role in the regulation of hibernation and (2) their secondary response to physiological changes during hibernation. The author's investigations described in this review have mainly been performed in European hedgehogs (Erinaceus europaeus), European and golden hamsters (Cricetus cricetus, Mesocricetus auratus), dormice (Glis glis), and in Richardson's and Columbian ground squirrels (Spermophilus richardsonii, Spermophilus columbianus), by the use of light- and electron-microscopic immunocytochemistry and histochemistry, in situ hybridization, radioimmunoassays and stereotaxically guided application techniques. These experiments were also performed in hypothermic animals. The (partially published) results obtained by the author and his associates are reviewed with reference to the body of evidence found in the recent literature. With respect to their reactivity patterns, several neuropeptide and transmitter systems can be regarded as candidates for control systems of hibernation. Neuronal complexes immunoreactive for endogenous opiates, in particular enkephalin, and also for vasopressin, somatostatin, substance P, corticotropin-releasing factor and serotonin are probably involved in the neuroendocrine control of hibernation.

Animals↗

Taxonomic study of keratinophilic fungi isolated from soil and some mammals in France.

In France, most of the researches have showed the distribution of dermatophytes and other keratinophilic fungi in the soil and in the coat of wild mammals. During these last years, we have also practiced numerous investigations about the distribution of such fungi. The isolated species are: Trichophyton mentagrophytes, Trichophyton terrestre, Trichophyton ajelloï, Trichophyton simii, Microsporum gypseum, Microsporum cookei, Microsporum nanum, Microsporum persicolor, Anixiopsis stercoraria, Chrysosporium keratinophilum, Chrysosporium tropicum, Chrysosporium state of Arthroderma curreyi, Chrysosporium state of Arthroderma cuniculi, Chrysosporium state of Arthroderma tuberculatum, Chrysosporium state of Arthroderma multifidum, Ctenomycès serratus, Chrysosporium parvum, Chrysosporium indicum, Chrysosporium georgii, Chrysosporium merdarium, Chrysosporium asperatum, Chrysosporium pannorum. A key to these species is proposed: it attempts to provide an aid in identifying geophilic dermatophytes and related fungi (belonging to the Chrysosporium genus).

Animals↗

Conservation of a cytoplasmic carboxy-terminal domain of connexin 43, a gap junctional protein, in mammal heart and brain.

According to the sequence of connexin 43, a cardiac gap junctional protein, the domain contained within residues 314-322 is located 60 amino acids away from the carboxy-terminus. Antibodies raised to a peptide corresponding to this domain label a unique 43-kD protein on immunoblots of both purified gap junctions and whole extracts from rat heart. Immunofluorescence investigations carried out on mammal heart sections reveal a pattern consistent with the known distribution of intercalated discs. Immunogold labeling performed with ultrahin frozen sections of rat heart or partially purified rat heart gap junctions demonstrate that antigenic determinants are associated exclusively with the cytoplasmic surfaces of gap junctions. The antibodies were shown to cross-react with a 43-kD protein on immunoblots of whole extracts from human, mouse and guinea pig heart. However, no labeling was seen when heart of lower vertebrates such as chicken, frog and trout, was investigated. These results, confirmed by immunofluorescence investigations, were interpreted as a loss of antigenic determinants due to sequence polymorphism of cardiac connexin 43. Proteins of Mr 43 and 41 kD, immunologically related to cardiac connexin 43, were detected in immunoblots of mouse and rat brain whole extracts. mRNAs, homologous to those of cardiac connexin 43 and of the same size (3.0 kb), are also present in brain. Immunofluorescence investigations with primary cultures of unpermeabilized and permeabilized mouse neural cells showed that the antigenic determinants recognized by the antibodies specific for connexin 43 are cytoplasmic and that the labeling observed between clustered flat cells, is punctate, as expected for gap junctions. Double labeling experiments demonstrated that the immunoreactivity is associated with GFAP-positive cells, that is to say, astrocytes.

Amino Acid Sequence↗

Molecular basis governing primary sex in mammals.

The function of Sry for inducing a male gonad was identified due to a development of a transgenic XX male mouse with testes by introducing a single gene into an embryo. The intronless Sry encodes a putative transcriptional protein harboring an HMG motif. The sequence similarity within the HMG motif has been highly conserved despite less conservation in other domains. Hence, the HMG motif must play a critical role in the transcriptional regulation, leading to the development of a male gonad. However, a non HMG box C terminal domain of Sry protein may also be indispensable for inducing normal testicular development. Further, several autosomal genes, such as SF1, WT1, SOX and MIS, as well as a unique X chromosomal DAX1 were suggested to be associated with the development of gonadal sex in mammals. Therefore, the significance on the involvement of these genes in the molecular mechanism of mammalian sex determination should be also considered.

Amino Acid Sequence↗

Different rates of substitution may produce different phylogenies of the eutherian mammals.

In an attempt to resolve some points of branching order in the phylogeny of the eutherian mammals, a phylogenetic analysis of 26 nuclear and 6 mitochondrial genes was undertaken using a maximum likelihood method on a constant rate stochastic model of molecular evolution. Seventeen of the nuclear genes gave a primates/artiodactyls grouping highest support whereas three of the mitochondrial genes found a rodents/artiodactyls grouping to be best supported. The primates/rodents grouping was never the best supported. On the assumption that rodents are indeed an outgroup to primates and artiodactyls and that the latter taxa diverged 70 million years ago, an estimation was made, for each gene, of the time of divergence of the rodent lineage. In most cases such estimates were beyond the limits set by present interpretations of the paleontological record as were many estimates of the divergence time of mouse and rat. These results suggest that, although there is locus variation, the divergent position of the rodent lineage may be an artifact of an elevated rate of nucleotide substitution in this order.

Animals↗

The branching order of mammals: phylogenetic trees inferred from nuclear and mitochondrial molecular data.

In order to clarify some controversial phylogenies such as those regarding the triplet of human, rodent, and cow and the evolutionary position of Lagomorpha with respect to other mammals, we have analyzed both nuclear and mitochondrial genes using the stationary Markov model developed in our laboratory. We found that the two sets of genes give different results. In particular the mitochondrial tree showed rabbit linked first to rodents and the rabbit-rodents branch linked to artiodactyls with human as the outgroup. The most favorite nuclear tree showed human linked first to artiodactyls and the human-artiodactyls branch linked to rabbit with rodents as the outgroup. The obvious questions, (1) which tree is the correct one, or (2) both trees can be incorrect, and (3) how can we explain such an evolutionary pattern, are discussed on the basis of our limited knowledge of factors that influence the clocklike behavior of biological macromolecules.

Animals↗

A study of parasitic infections in mammals and birds at the Dublin Zoological Gardens.

The present report deals with the parasitic infections detected on examination of fresh faecal samples of 48 mammals and 4 birds at the Zoological Gardens, Dublin during 1978-79. 1,822 faecal samples were received over the two year period and 171 of these samples contained helminth eggs. Ninety-five percent of these positive findings were confined to the Carnivore and Herbivore groups with the Primates, Marsupials and Avians showing a low level of intestinal parasites.

Animals↗

Distribution of HEOD (dieldrin) in mammals: II. some applications of the preliminary model.

The preliminary model of the lipid-phase pharmacokinetics of dieldrin in mammals is applied to evaluation of the probable role of auto-induction, the effect(s) of growth, and the role of compartmentalization. Realistic simulations and comparison to actual data permit the conclusion to be drawn that induction of its own metabolism plays a relatively monor role in the distribution and level of dieldrin residues. Although some of the effects of growth are resonably well simulated, the model as constructed does not permit compartmentalization. It was concluded that the model should be revised to include aspects of the as-yet quantitatively unknown intracellular binding and membrane transport within the flow-limited model.

Adipose Tissue↗

Lens protein expression in mammals: taxon-specificity and the recruitment of crystallins.

Vertebrate lenses show remarkably taxon-specific patterns of protein composition, most obviously in the recruitment of enzymes as major crystallins. Phylogenetic relationships are particularly apparent in mammals. Here we describe eta-crystallin, which is probably identical to cytosolic aldehyde dehydrogenase, lens-specifically expressed at high abundance in the elephant shrews, primitive eutherians of the family Macroscelidae, and mu-crystallin, a novel lens protein expressed in some marsupials. We have also observed that enzymes that have been recruited as crystallins in some species are also moderately abundant in the lenses of other species. This hints that the origins of enzyme-crystallins may lie in a pool of enzymes widely expressed in lenses at fairly high levels, perhaps because they have important developmental or functional roles in the tissue.

Alcohol Dehydrogenase↗

Evolution of the cytochrome b gene of mammals.

With the polymerase chain reaction (PCR) and versatile primers that amplify the whole cytochrome b gene (approximately 1140 bp), we obtained 17 complete gene sequences representing three orders of hoofed mammals (ungulates) and dolphins (cetaceans). The fossil record of some ungulate lineages allowed estimation of the evolutionary rates for various components of the cytochrome b DNA and amino acid sequences. The relative rates of substitution at first, second, and third positions within codons are in the ratio 10 to 1 to at least 33. For deep divergences (greater than 5 million years) it appears that both replacements and silent transversions in this mitochondrial gene can be used for phylogenetic inference. Phylogenetic findings include the association of (1) cetaceans, artiodactyls, and perissodactyls to the exclusion of elephants and humans, (2) pronghorn and fallow deer to the exclusion of bovids (i.e., cow, sheep, and goat), (3) sheep and goat to the exclusion of other pecorans (i.e., cow, giraffe, deer, and pronghorn), and (4) advanced ruminants to the exclusion of the chevrotain and other artiodactyls. Comparisons of these cytochrome b sequences support current structure-function models for this membrane-spanning protein. That part of the outer surface which includes the Qo redox center is more constrained than the remainder of the molecule, namely, the transmembrane segments and the surface that protrudes into the mitochondrial matrix. Many of the amino acid replacements within the transmembrane segments are exchanges between hydrophobic residues (especially leucine, isoleucine, and valine). Replacement changes at first and second positions of codons approximate a negative binomial distribution, similar to other protein-coding sequences. At four-fold degenerate positions of codons, the nucleotide substitutions approximate a Poisson distribution, implying that the underlying mutational spectrum is random with respect to position.

Amino Acid Sequence↗

Absorption and transport of fat in mammals with emphasis on n-3 polyunsaturated fatty acids.

The current state of knowledge concerning the absorption and transport of dietary fat with emphasis on long-chain polyunsaturated n-3 fatty acids in mammals is reviewed. It is apparent that long-chain polyunsaturated n-3 fatty acids, either as free acids or as part of triglycerides, are readily absorbed in the gut and transported by the circulatory system. Indeed, it would appear that long-chain polyunsaturated n-3 fatty acids are digested, absorbed and transported similarly to other long-chain fatty acids with only minor variations, although there is much that is still not understood about these processes. The main unresolved issues in the area of the absorption and transport of long-chain polyunsaturated n-3 fatty acids appear to be: 1) If they, when located in the 2-position of triglycerides, have unique metabolic pathways; and 2) whether the unnatural forms, i.e., methyl or ethyl ester derivatives, are suitable vehicles for administration as dietary supplements. The effect in man of dietary, long-chain polyunsaturated n-3 fatty acids on blood serum lipid and lipoprotein levels, particularly the low density lipoproteins, remains controversial, except for the well-documented reduction in serum triglyceride levels. Also, there is uncertainty regarding their distribution and metabolism in tissues. Finally, if the consumption of long-chain polyunsaturated n-3 fatty acids has beneficial health consequences, what is the appropriate therapeutic dose? In view of these important, unresolved issues and uncertainties, it would seem prudent to direct additional research toward a better understanding of the overall process by which fat is digested, absorbed and transported.

Animals↗

The composition of red cell membrane phospholipids in Canadian Inuit consuming a diet high in marine mammals.

A study of the fatty acid composition of red cell phosphatidylcholine and phosphatidylethanolamine and serum cholesterol was undertaken in 185 Canadian Inuit (age 2 months-82 years). Samples from 24 Canadian men and women (21-50 years) living in Vancouver were also analyzed as a reference for the Inuit in this age range. Dietary survey of the Inuit community (325 Inuit) demonstrated a diet based on traditional foods in which the principal source of n-3 fatty acid was marine mammal flesh (mean intake: 164 g/person/day) rather than fish (mean intake: 13 g/person/day). Compared to the Vancouver samples, the Inuit phosphatidylethanolamine had higher 20:5n-3 and 22:6n-3 and lower 20:4n-6, but similar 18:2n-6 levels. The level of 20:5n-3 was higher and 20:4n-6 was lower in the Inuit than in the Vancouver red cell phosphatidylcholine. Despite these differences in percentage content of C20 and C22 n-6 and n-3 fatty acids, the mean chain length and unsaturation index of the Inuit and Vancouver red cell phosphatidylcholine and phosphatidylethanolamine were very similar. Serum cholesterol concentration showed no sex difference within the Inuit, and no difference from Vancouver men and women of similar age. The analyses suggest that the fatty acid composition of the Inuit red cell phospholipids are primarily a reflection of their diet-fat composition.

Adolescent↗