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PubMed1997

Evolution of processes and regulators of lipoprotein synthesis: from birds to mammals.

Mammalian lipoproteins are synthesized in the liver and secreted into the blood plasma where they are targeted to specific tissues. Through specific cell surface receptors, hepatic lipoproteins are taken up and their lipid contents are then used for anabolic and energy requirements. Because of the well-established role that plasma lipoproteins play as risk factors for the development of cardiovascular disease, a great amount of attention has been directed toward understanding their metabolism and biosynthesis. The major focus of this report is to review the evolution of gene products that are essential in regulating, synthesizing, assembling and secreting the lipid and protein components of lipoproteins. Using the primordial vitellogenin lipoprotein system as the paradigm, I show how metabolic signals derived from the sterol biosynthetic pathway provide a coordinate regulation of genes necessary to assemble and secrete mammalian apolipoprotein B-containing lipoproteins. In lower species, estrogen induces the expression of genes required for both vitellogenin synthesis and its tissue targeting (the vitellogenin receptor). This coordinate induction provides lipid to the ovaries for egg development. In mammals, a sterol-derived metabolic signal regulates the expression of genes required for lipoprotein synthesis and for the LDL receptor. The signal is not sex linked, providing an adaptive advantage to changes in nutritional status.

Animals↗
PubMed2004

How strong is the mutagenicity of recombination in mammals?

It is commonly believed that a high recombination rate such as that in a pseudoautosomal region (PAR) greatly increases the mutation rate because a 170-fold increase was estimated for the mouse PAR region. However, sequencing PAR and non-PAR introns of the Fxy gene in four Mus taxa, we found an increase of only twofold to fivefold. Furthermore, analyses of sequence data from human and orangutan PAR and X-linked regions and from autosomal regions showed a weak effect of recombination on mutation rate (a slope of less than 0.2% per cM/Mb), although a much stronger effect on GC content (1% to 2% per cM/Mb). Because typical recombination rates in mammals are much lower than those in PARs, the mutagenicity of recombination is weak or, at best, moderate, although its effect on GC% is much stronger. In addition, contrary to a previous study, we found no Fxy duplicate in Mus spretus.

Animals↗
PubMed1991

The genetic control and germ cell kinetics of the female and male germ line in mammals including man.

The female germ line (germ cell lineage, Keimbahn) is provided with only one proliferation wave, the oogenic, whereas male gametogenesis involves two successive waves: prespermatogenic, which corresponds to the female proliferation wave, and spermatogenesis, which is responsible for the immense number of male gametes produced in mature testes. Both male proliferation systems are linked by the transitional or T prospermatogonia. Using the reverse percentage of labelled metaphases method, it has been shown that the first differences between female and male germ cells can be identified by the end of the first wave, when oogonia and multiplying or M prospermatogonia are proliferating. This prenatal first wave of proliferation of male germ cells was also demonstrated in man and ceases around the 22nd week of pregnancy. Spermatogenesis involves a stock of stem cells (stem spermatogonia), a flexibly reacting pool of undifferentiated spermatogonia and several generations of differentiating spermatogonia, which proliferate almost exponentially. Furthermore, it consists of spermatocytes and haploid spermatids transforming into spermatozoa. The oocytes pass through the preleptotene stage, synthesizing DNA, and thereafter traverse the meiotic prophase up to the diplotene stage. In mammals they act as 'pre-embryos' in a similar but to a lesser degree than oocytes of amphibia and insects. The maternal chromosomes are largely responsible for the development of the embryo, the paternal genome for the development of the extra-embryonic tissue. The synthesis of transgenic animals is a powerful weapon in the armoury of geneticists, as has recently been demonstrated: a 14 kb genomic DNA fragment (Sry) is sufficient to induce testis differentiation and subsequent male development when introduced into chromosomally female mouse embryos.

Animals↗
PubMedDate not supplied

Parthenogenesis, homozygosity, and cloning in mammals.

The numerous strategies for reproduction, sexual and asexual, that have evolved, suggest experimental designs for altering the reproduction of any particular species. The ability to culture and manipulate mammalian eggs and embryos in vitro provides the technological basis for experimentally altering the reproduction of mammals and can lead to the generation of new and useful genotypes. All of these advances, however, are restricted by our lack of understanding of the chromosomal mechanisms by which genes are regulated during the course of cell differentiation. An attractive hypothesis postulates that programs of gene regulation during development are based upon topographic interactions among chromosomes in the interphase nucleus and that these interactions in turn require an appropriate positioning of regulatory DNA throughout the genome.

Animals↗
PubMed1999

Isolation of novel GRO genes and a phylogenetic analysis of the CXC chemokine subfamily in mammals.

Approximately 15 different alpha, or CXC, chemokines have thus far been isolated from 11 species of mammals. Among the best studied chemokines are the 12 human proteins that are encoded by 11 paralogous genes. In order to better understand the evolution and function of this group of genes, we isolated and characterized six novel GRO and GRO-related cDNA sequences from the cow (Bos taurus), the sheep (Ovis aries), the rabbit (Oryctolagus cuniculus), and the guinea pig (Cavia porcellus). The amino acid sequence of the diverged guinea pig GRO or KC gene is only 50%-60% similar to presumed orthologs from other species, while the sheep and cow GRO proteins are 90%-99% similar to each other. The presence of multiple GRO genes in the cow, the rabbit, and the sheep is consistent with what has been observed for humans. Phylogenetic analyses of amino acid sequences from 44 proteins indicate that genes orthologous to many of the 11 known from humans exist in other species. One such gene, interleukin 8, or IL8, has been isolated from nine species, including the rodent guinea pig; however, this gene is absent in the rat and the mouse, indicating a unique gene loss event in the rat/mouse (muroid rodent) lineage. The KC (or MIP2) gene of rodents appears to be orthologous to the GRO gene found in other taxonomic orders. Combined evidence from different sources suggests that IP10 and MIG share sister taxon relationships on the evolutionary tree, while the remaining paralogous genes represent independent lineages, with limited evidence for kinship between them. This observation indicates that these genes originated nearly contemporaneously via a series of gene duplication events. Relative-rate tests for synonymous and nonsynonymous nucleotide substitutions in the KC and IL8 genes did not detect rate heterogeneity; however, there are several notable features regarding the IL8 genes. For example, the IL8 proteins from two Old World monkeys are as similar to one another as they are to the IL8 protein from humans, and all observed nucleotide differences between the IL8 genes of the two monkeys cause amino acid changes; in other words, there are no synonymous differences between them.

Amino Acid Sequence↗
PubMed2003

Towards a model for the dynamic transfer of tritium and carbon in mammals.

Available data have been analysed to test the hypothesis that both 3H and 14C transfer in mammals can be accounted for by an understanding of metabolism. Data obtained from various 14C and 3H experiments with rats and sheep have been analysed to assess the multi-component retention function of various organs and identify any relationship between half-times and component contribution. Our hypothesis was that component half-times for 14C and 3H are similar after intakes of organic compounds. Similarities in the tritium and carbon dynamics between rat and sheep were observed supporting the hypothesis. For fast and slow components of muscle half-time, allometric relationships have been derived. The results obtained could be used in the development of a human biokinetic model.

Adipose Tissue↗
PubMed2006

Gene expression profiles in fathead minnow exposed to 2,4-DNT: correlation with toxicity in mammals.

Toxicogenomics, the genome-wide analysis of gene expression to study the effect of toxicants, has great potential for use in environmental toxicology. Applied to standard test organisms, it has possible applications in aquatic toxicology as a sensitive monitoring tool to detect the presence of contaminants while providing information on the mechanisms of action of these pollutants. We describe the use of a complementary DNA (cDNA) microarray of the fathead minnow (Pimephales promelas) a standard sentinel organism in aquatic toxicology, to better understand the mechanisms of toxicity of 2,4-dinitrotoluene (2,4-DNT) which is released in the environment through military and industrial use. We have constructed a fathead minnow microarray containing 5000 randomly picked anonymous cDNAs from a whole fish cDNA library. Expression profiles were analyzed in fish exposed to 2,4-DNT for 10 days at three concentrations (11, 22, and 44 microM, respectively) below the measured median lethal concentration (58 microM). Sequence analysis of cDNAs corresponding to differentially expressed genes affected by exposure revealed that lipid metabolism and oxygen transport genes were prominently affected in a dose-specific manner. We measured liver lipids and demonstrate that lipid metabolism is indeed perturbed following exposure. These observations correlate well with available toxicological data on 2,4-DNT. We present possible modes of action of 2,4-DNT toxicity and suggest that fathead minnow cDNA microarrays can be useful to identify mechanisms of toxicity in fish and as a predictive tool for toxicity in mammals.

Animals↗
PubMed1983

Significance of the need for sperm capacitation before fertilization in eutherian mammals.

In order to fertilize, the spermatozoa of eutherian mammals must undergo capacitation in the female tract. The subcellular changes involved in capacitation finally seem to permit the influx of Ca2+ required for onset of the acrosome reaction, and they result also in a hyperactivated form of motility. However, why capacitation has appeared as an essential prerequisite for eutherian fertilization is unknown. Both these facets of capacitation may reflect new cellular control mechanisms for regulating the sperm's activities, necessitated by evolutionary change in the oocyte. The first may reflect a loss of the oocyte's stimulation of the acrosome reaction, and the second a concomitant appearance of unusually formidable egg vestments the spermatozoon must penetrate. Coordination of the rate of capacitation appropriate to fertilization in vivo may depend not only on the minimal time ordained for the species, but also on a heterogeneity among subpopulations of spermatozoa within any one sample and the timing of sperm transport to the oviduct.

Acrosome↗
PubMed2000

Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals.

DNA damage is considered of paramount importance in aging. Among causes of this damage, free radical attack, particularly from mitochondrial origin, is receiving special attention. If oxidative damage to DNA is involved in aging, long-lived animals (which age slowly) should show lower levels of markers of this kind of damage than short-lived ones. However, this possibility has not heretofore been investigated. In this study, steady-state levels of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG) referred to deoxyguanosine (dG) were measured by high performance liquid chromatography (HPLC) in the mitochondrial (mtDNA) and nuclear (nDNA) DNA from the heart of eight and the brain of six mammalian species ranging in maximum life span (MLSP) from 3.5 to 46 years. Exactly the same digestion of DNA to deoxynucleosides and HPLC protocols was used for mtDNA and nDNA. Significantly higher (three- to ninefold) 8-oxodG/dG values were found in mtDNA than in nDNA in all the species studied in both tissues. 8-oxodG/dG in nDNA did not correlate with MLSP across species either in the heart (r=-0.68; P<0.06) or brain (r = 0.53; P<0.27). However, 8-oxodG/dG in mtDNA was inversely correlated with MLSP both in heart (r=-0.92; P<0.001) and brain (r=-0.88; P<0.016) tissues following the power function y = a(.)x(b), where y is 8-oxodG/dG and x is the MLSP. This agrees with the consistent observation that mitochondrial free radical generation is also lower in long-lived than in short-lived species. The results obtained agree with the notion that oxygen radicals of mitochondrial origin oxidatively damage mtDNA in a way related to the aging rate of each species.-Barja, G., Herrero, A. Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

Disparate evolution of prion protein domains and the distinct origin of Doppel- and prion-related loci revealed by fish-to-mammal comparisons.

Prions result from the misfolding and selective accumulation of the host-encoded prion protein (PrP) in the brain. Despite intensive research on mammalian models, basic questions about the biological role of PrP and the evolutionary origin of prion disease remain unanswered. Following our previous identification of novel fish PrP homologues, here we generated new fish PrP sequences and performed genomic analysis to demonstrate the existence of two homologous PrP loci in bony fish, which display extensive molecular variation and are highly expressed in adult and developing fish brains. The fish PrP genomic regions contain PrP-related loci directly downstream of each PrP locus, suggesting an independent origin of prion-related proteins in fish and mammals. Our structural prediction analysis uncovers a conserved molecular "bauplan" for all vertebrate PrPs. The C- and N-terminal protein domains have evolved independently from one another, the former having retained its basic globular structure despite high sequence divergence and the latter having undergone differential expansion-degeneration cycles in its repetitive domains. Our evolutionary analysis redefines fundamental concepts on the functional significance of PrP domains and opens up new possibilities for the experimental analysis of prion misfolding and neurodegeneration in a non-mammalian model like the zebrafish.

Amino Acid Sequence↗
PubMed1991

Sperm competition influences sperm size in mammals.

Among mammals sperm competition leads to selection for increased sperm numbers but it is not known whether it also leads to changes in sperm size. Two contrasting theoretical predictions have been made. The first hypothesis relies on the assumption that there is a trade-off between sperm numbers and sperm size and predicts that, in species confronting sperm competition, there will be a concomitant decrease in sperm size as sperm numbers increase. In contrast, the second hypothesis suggests that longer sperm may outcompete rival sperm; if longer sperm may swim faster, they will reach the ova sooner and will be selected when sperm competition prevails. We tested these hypotheses in both primates and rodents. We report that males from species in which females mate promiscuously have longer sperm than species in which females mate with one male. In addition, we also found that sperm length is positively correlated with maximum sperm velocity. Our findings thus support the view that longer sperm may be adaptive in the context of sperm competition.

Adaptation, Physiological↗
PubMed1993

Coevolution between male ejaculates and female reproductive biology in eutherian mammals.

Among eutherian mammals, sperm competition has favoured the evolution of high sperm numbers and long spermatozoa, but it cannot account for all the variability observed. In this paper we argue that differences in female reproductive biology may also have influenced the evolution of sperm numbers as well as several other sperm traits. Sperm fertile lifespan is positively related to the interval between the onset of oestrus and ovulation, suggesting that males try to ensure that their spermatozoa will remain capable of effecting fertilization until ovulation occurs. We tentatively suggest that variation in sperm fertile lifespan may be related to differences in sperm size. The duration of capacitation is positively related to sperm fertile lifespan, suggesting that the time constraints imposed by the female have also influenced the duration of this process. When females possess long oviducts in relation to their body size, males produce relatively high sperm numbers to counteract the greater losses incurred. Contrary to our prediction, sperm size does not seem to be related to the thickness of the zona pellucida.

Animals↗
PubMed1997

An optimization model for mastication and swallowing in mammals.

Mammalian mastication is a process combining simultaneous food comminution and lubrication. The initiation of swallowing, which is voluntary, has been thought to depend on separate thresholds for food particle size and for particle lubrication. Instead of this duality, we suggest that swallowing is initiated when it is sensed that a batch of food particles is binding together under viscous forces so as to form a bolus. Bolus formation ensures that when the food mass is swallowed, it will pass the pharyngeal region safely without risk of inhaling small particles into the lower respiratory tract. Crucial for bolus formation is food particle size reduction by mastication. This allows the tongue to pack particles together tightly by pressure against the hard palate. A major function of salivation is to fill the gradually reducing spaces between particles, so increasing viscous cohesion and promoting bolus formation. If swallowing is delayed, excessive saliva floods the bolus, separating particles and reducing cohesion. Swallowing then becomes more precarious. Our model suggests that there is an optimum moment for a mammal to swallow, defined in terms of a peak cohesive force between food particles. The model is tested on human mastication with two foods, brazil nut and raw carrot, which have very different particle size breakdown rates. The peak cohesive force is much greater with brazil nuts but both foods are predicted to be swallowed after similar numbers of chews despite the very different food particle size reductions achieved at that stage. The predicted number of chews to swallow is in broad agreement with published data.

Animals↗
PubMed1999

Heritable variation in resistance to gastro-intestinal nematodes in an unmanaged mammal population.

The impact of parasites on natural populations has received considerable attention from evolutionary biologists in recent years. Central to a number of theoretical developments during this period is the assumption of additive genetic variation in resistance to parasites. However, very few studies have estimated the heritability of parasite resistance under field conditions, and those that have are mainly restricted to birds and their ectoparasites. In this paper, to our knowledge, we show for the first time in a free-ranging mammal population, Soay sheep (Ovis aries) living on the islands of St Kilda, that there is significant heritable variation in resistance to gastrointestinal nematodes. This result is consistent with earlier studies on this population which have indicated locus-specific associations with parasite resistance. We discuss our results in the context of current studies examining heritable resistance to parasites in domestic sheep and the possible mechanisms of selective maintenance of genetic variation for resistance to gastrointestinal nematodes in the St Kilda Soay sheep population.

Animals↗
PubMed2002

Sexual selection and speciation in mammals, butterflies and spiders.

Recently refined evolutionary theories propose that sexual selection and reproductive conflict could be drivers of speciation. Male and female reproductive optima invariably differ because the potential reproductive rate of males almost always exceeds that of females: females are selected to maximize mate 'quality', while males can increase fitness through mate 'quantity'. A dynamic, sexually selected conflict therefore exists in which 'competitive' males are selected to override the preference tactics evolved by 'choosy' females. The wide variation across taxa in mating systems therefore generates variance in the outcome of intrasexual conflict and the strength of sexual selection: monandry constrains reproductive heterozygosity and allows female choice to select and maintain particular (preferred) genes; polyandry promotes reproductive heterozygosity and will more likely override female choice. Two different theories predict how sexual selection might influence speciation. Traditional ideas indicate that increased sexual selection (and hence conflict) generates a greater diversity of male reproductive strategies to be counteracted by female mate preferences, thus providing elevated potentials for speciation as more evolutionary avenues of male-female interaction are created. A less intuitively obvious theory proposes that increased sexual selection and conflict constrains speciation by reducing the opportunities for female mate choice under polyandry. We use a comparative approach to test these theories by investigating whether two general measures of sexual selection and the potential for sexual conflict have influenced speciation. Sexual size dimorphism (across 480 mammalian genera, 105 butterfly genera and 148 spider genera) and degree of polyandry (measured as relative testes size in mammals (72 genera) and mating frequency in female butterflies (54 genera)) showed no associations with the variance in speciosity. Our results therefore show that speciation occurs independently of sexual selection.

Animals↗
PubMed2003

Telomeres shorten more slowly in long-lived birds and mammals than in short-lived ones.

We know very little about physiological constraints on the evolution of life-history traits in general, and, in particular, about physiological and molecular adjustments that accompany the evolution of variation in lifespan. Identifying mechanisms that underlie adaptive variation in lifespan should provide insight into the evolution of trade-offs between lifespan and other life-history traits. Telomeres, the DNA caps at the ends of linear chromosomes, usually shorten as animals age, but whether telomere rate of change is associated with lifespan is unknown. We measured telomere length in erythrocytes from five bird species with markedly different lifespans. Species with shorter lifespans lost more telomeric repeats with age than species with longer lifespans. A similar correlation is seen in mammals. Furthermore, telomeres did not shorten with age in Leach's storm-petrels, an extremely long-lived bird, but actually lengthened. This novel finding suggests that regulation of telomere length is associated not only with cellular replicative lifespan, but also with organismal lifespan, and that very long-lived organisms have escaped entirely any telomeric constraint on cellular replicative lifespan.

Aging↗
PubMed2004

Adaptive evolution of HoxA-11 and HoxA-13 at the origin of the uterus in mammals.

The evolution of morphological characters is mediated by the evolution of developmental genes. Evolutionary changes can either affect cis-regulatory elements, leading to differences in their temporal and spatial regulation, or affect the coding region. Although there is ample evidence for the importance of cis-regulatory evolution, it has only recently been shown that transcription factors do not remain functionally equivalent during evolution. These results suggest that the evolution of transcription factors may play an active role in the evolution of development. To test this idea we investigated the molecular evolution of two genes essential for the development and function of the mammalian female reproductive organs, HoxA-11 and HoxA-13. We predicted that if coding-region evolution plays an active role in developmental evolution, then these genes should have experienced adaptive evolution at the origin of the mammalian female reproductive system. We report the sequences of HoxA-11 from basal mammalian and amniote taxa and analyse HoxA-11 and HoxA-13 for signatures of adaptive molecular evolution. The data demonstrate that these genes were under strong positive (directional) selection in the stem lineage of therian and eutherian mammals, coincident with the evolution of the uterus and vagina. These results support the idea that adaptive evolution of transcription factors can be an integral part in the evolution of novel structures.

Adaptation, Biological↗
PubMed2004

Sexual selection and the risk of extinction in mammals.

Sexual selection is commonly envisaged as a force working in opposition to natural selection, because extravagant or exaggerated traits could apparently have never evolved via natural selection alone. There is good evidence that a selection load imposed by sexual selection may be eased experimentally by restricting the opportunity for it to operate. Sexual selection could therefore potentially play an important role in influencing the risk of extinction that a population faces, thereby contributing to the apparent selectivity of extinctions. Conversely, recent theory predicts that the likelihood of extinction may decrease when sexual selection is operating because it could accelerate the rate of adaptation in concert with natural selection. So far, comparative evidence (coming mostly from birds) has generally indicated support for the former scenario, but the question remains open. The aim of this study was therefore to examine whether the level of sexual selection (measured as residual testes mass and sexual size dimorphism) was related to the risk of extinction that mammals are currently experiencing. We found no evidence for a relationship between these factors, although our analyses may have been confounded by the possible dominating effect of contemporary anthropogenic factors.

Animals↗