How do insect nuclear and mitochondrial gene substitution patterns differ? Insights from Bayesian analyses of combined datasets

We analyzed 12 combined mitochondrial and nuclear gene datasets in seven orders of insects using both equal weights parsimony (to evaluate phylogenetic utility) and Bayesian methods (to investigate substitution patterns). For the Bayesian analyses we used relatively complex models (e.g., general time reversible models with rate variation) that allowed us to quantitatively compare relative rates among genes and codon positions, patterns of rate variation among genes, and substitution patterns within genes. Our analyses indicate that nuclear and mitochondrial genes differ in a number of important ways, some of which are correlated with phylogenetic utility. First and most obviously, nuclear genes generally evolve more slowly than mitochondrial genes (except in one case), making them better markers for deep divergences. Second, nuclear genes showed universally high values of CI and (generally) contribute more to overall tree resolution than mitochondrial genes (as measured by partitioned Bremer support). Third, nuclear genes show more homogeneous patterns of among-site rate variation (higher values of alpha than mitochondrial genes). Finally, nuclear genes show more symmetrical transformation rate matrices than mitochondrial genes. The combination of low values of alpha and highly asymmetrical transformation rate matrices may explain the overall poor performance of mitochondrial genes when compared to nuclear genes in the same analysis. Our analyses indicate that some parameters are highly correlated. For example, A/T bias was positively and significantly associated with relative rate and CI was positively and significantly associated with alpha (the shape of the gamma distribution). These results provide important insights into the substitution patterns that might characterized high quality genes for phylogenetic analysis: high values of alpha, unbiased base composition, and symmetrical transformation rate matrices. We argue that insect molecular systematists should increasingly focus on nuclear rather than mitochondrial gene datasets because nuclear genes do not suffer from the same substitutional biases that characterize mitochondrial genes.     

Environmentally caused dwarfism or a valid species--is Testudo weissingeri Bour, 1996 a distinct evolutionary lineage? New evidence from mitochondrial and nuclear genomic markers

We examine the evolutionary relationships of the five traditionally recognized species of the western Palearctic tortoise genus Testudo (T. graeca, T. hermanni, T. horsfieldii, T. kleinmanni, and T. marginata) and the newly described dwarfed species T. weissingeri by using sequence data of the mitochondrial cytochrome b gene and nuclear genomic fingerprints with inter-simple sequence repeats (ISSR). Testudo weissingeri differs from T. marginata mainly by its smaller size and some color-pattern characteristics. T. weissingeri lives in the driest, poorest and hottest part of the distributional range of T. marginata. While both data sets demonstrated phylogenetic distinctness of the five traditionally recognized species of Testudo, some subspecies and even some local populations, we detected no differentiation between T. marginata and T. weissingeri. We conclude that T. weissingeri is not a distinct evolutionary unit. We suggest that its small size is the result of suboptimal environmental conditions with limited resources and synonymize it with T. marginata. T. marginata and T. kleinmanni form a clade that is supported both by our mtDNA and nuclear genomic data sets. According to mtDNA data, this clade is the sister taxon to the T. graeca complex. A sister group relationship of T. hermanni and ((T. marginata+T. kleinmanni)+T. graeca) is moderately to weakly supported by mtDNA data; T. horsfieldii is the sister taxon to a clade comprising all other Testudo species.     

The inheritance of mitochondrial DNA heteroplasmy: random drift, selection or both?

The mammalian mitochondrial genome (mtDNA) is a small double-stranded DNA molecule that is exclusively transmitted down the maternal line. Pathogenic mtDNA mutations are usually heteroplasmic, with a mixture of mutant and wild-type mtDNA within the same organism. A woman harbouring one of these mutations transmits a variable amount of mutant mtDNA to each offspring. This can result in a healthy child or an infant with a devastating and fatal neurological disorder. Understanding the biological basis of this uncertainty is one of the principal challenges facing scientists and clinicians in the field of mitochondrial genetics.     

The Warburg effect and mitochondrial oxidative phosphorylation: Friends or foes?

Cancer cells display an altered energy metabolism, which was proposed to be the root of cancer. This early discovery was done by O. Warburg who conducted one of the first studies of tumor cell energy metabolism. Taking advantage of cancer cells that exhibited various growth rates, he showed that cancer cells display a decreased respiration and an increased glycolysis proportional to the increase in their growth rate, suggesting that they mainly depend on fermentative metabolism for ATP generation.Warburg's results and hypothesis generated controversies that are persistent to this day. It is thus of great importance to understand the mechanisms by which cancer cells can reversibly regulate the two pathways of their energy metabolism as well as the functioning of this metabolism in cell proliferation. In this review, we discuss of the origin of the decrease in cell respiratory rate, whether the Warburg effect is mandatory for an increased cell proliferation rate, the consequences of this effect on two major players of cell energy metabolism that are ATP and NADH, and the role of the microenvironment in the regulation of cellular respiration and metabolism both in cancer cell and in yeast.     

Is mitochondrial DNA content a potential biomarker of mitochondrial dysfunction?

Mitochondrial dysfunction is central to numerous diseases of oxidative stress. Changes in mitochondrial DNA (MtDNA) content, often measured as mitochondrial genome to nuclear genome ratio (Mt/N) using real time quantitative PCR, have been reported in a broad range of human diseases, such as diabetes and its complications, obesity, cancer, HIV complications, and ageing. We propose the hypothesis that MtDNA content in body fluids and tissues could be a biomarker of mitochondrial dysfunction and review the evidence supporting this theory. Increased reactive oxygen species resulting from an external trigger such as hyperglycaemia or increased fat in conditions of oxidative stress could lead to enhanced mitochondrial biogenesis, and increased Mt/N. Altered MtDNA levels may contribute to enhanced oxidative stress and inflammation and could play a pathogenic role in mitochondrial dysfunction and disease. Changes in Mt/N are detectable in circulating cells such as peripheral blood mononuclear cells and these could be used as surrogate to predict global changes in tissues and organs. We review a large number of studies reporting changes in MtDNA levels in body fluids such as circulating blood cells, cell free serum, saliva, sperm, and cerebrospinal fluid as well as in tumour and normal tissue samples. However, the data are often conflicting as the current methodology used to measure Mt/N can give false results because of one or more of the following reasons (1) use of mitochondrial primers which co-amplify nuclear pseudogenes (2) use of nuclear genes which are variable and/or duplicated in numerous locations (3) a dilution bias caused by the differing genome sizes of the mitochondrial and nuclear genome and (4) template preparation protocols which affect the yields of nuclear and mitochondrial genomes. Development of robust and reproducible methodology is needed to test the hypothesis that MtDNA content in body fluids is biomarker of mitochondrial dysfunction.     

Is mitochondrial DNA a strictly neutral marker?

Variation and change in mitochondrial DNA (mtDNA) is often assumed to conform to a constant mutation rate equilibrium neutral model of molecular evolution. Recent evidence, however, indicates that the assumptions underlying this model are frequently violated. The mitochondria) genome may be subject to the same suite of forces known to be acting in the nuclear genome, including hitchhiking and selection, as well as forces that do not affect nuclear variation. Wherever possible, evolutionary studies involving mtDNA should incorporate statistical tests to investigate the forces shaping sequence variation and evolution.     

Extreme difference in rate of mitochondrial and nuclear DNA evolution in a large ectotherm, Galápagos tortoises

We sequenced approximately 4.5 kb of mtDNA from 161 individuals representing 11 named taxa of giant Galápagos tortoises (Geochelone nigra) and about 4 kb of non-coding nuclear DNA from fewer individuals of these same 11 taxa. In comparing mtDNA and nucDNA divergences, only silent substitutions (introns, ITS, mtDNA control region, and synonymous substitutions in coding sequences) were considered. mtDNA divergence was about 30 times greater than that for nucDNA. This rate discrepancy for mtDNA and nucDNA is the greatest yet documented and is particularly surprising for large ectothermic animals that are thought to have relatively low rates of mtDNA evolution. This observation may be due to the somewhat unusual reproductive biology and biogeographic history of these organisms. The implication is that the ratio of effective population size of nucDNA/mtDNA is much greater than the usually assumed four. The nearly neutral theory of molecular evolution predicts this would lead to a greater difference between rates of evolution.     

Interspecific hybridization, a matter of pioneering? Insights from Atlantic salmon and brown trout

Interspecific hybridization may occur in situations of recent contact between a colonizer and a resident species, being more intense in the colonization front. Atlantic salmon Salmo salar and brown trout S. trutta have been sympatric species since their origin and they share spatial and temporal spawning niches, exhibiting low levels of bidirectional interspecific hybridization and introgression throughout their distribution range. Different causes have been identified for increased hybridization, from escapes or deliberate releases of domesticated fish to sneaking male behavior. We have examined hybridization rates and direction in different situations of advance of one of these species into a territory formerly inhabited by the other (247 samples were analyzed in northern Spain and 487 in Kerguelen Islands). In all cases, hybrids found in the colonization front were offspring of colonizer females and resident males. We hypothesize that these findings are the result of adaptive relaxed mate choice of colonizing females, regardless of the relative abundance of each species.     

The evolution of Dianthus polylepis complex (Caryophyllaceae) inferred from morphological and nuclear DNA sequence data: one or two species?

Dianthus polylepis complex consists of two already known endemic species, Dianthus polylepis and D. binaludensis, in Khorassan-Kopetdagh floristic province. The taxonomic position of these species has long been debated. The aim of the present study is to shed light on the evolutionary relationships of the members of the complex using morphological and molecular data. In morphological study, firstly, 56 vegetative and floral characters were measured on 33 specimens of the both species. Multivariate analyses were performed on 25 (out of 56) significantly discriminating morphological traits. In molecular study, we sequenced alleles obtained from a region between 2nd and 6th exons of the gene coding for the enzyme dihydroflavonol 4-reductase copy1 (DFR1). Morphological results show that most of a priori identified accessions were not grouped in a posteriori classification. It is difficult to discriminate D. polylepis from D. binaludensis in morphological continuum among the accessions. Results obtained from the molecular data indicated no monophyly for the members of the D. polylepis complex. Consistency between the morphological and molecular results shows that D. polylepis and D. binaludensis were not morphologically and molecularly well differentiated. Therefore, we propose a new combination as D. polylepis subsp. binaludensis.     

The mitochondrial theory of aging: dead or alive?

The mitochondrial theory of aging is based around the idea of a vicious cycle, in which somatic mutation of mtDNA engenders respiratory chain dysfunction, enhancing the production of DNA-damaging oxygen radicals. In turn, this is proposed to result in the accumulation of further mtDNA mutations. Finally, a bioenergetic crisis leads to overt tissue dysfunction and degeneration. A substantial body of circumstantial evidence seems to support this idea. However, the extent of detectable mtDNA mutation is far less than can easily be reconciled to this hypothesis, unless it is assumed that a subset of cells with much higher than average mtDNA mutation load is systematically lost by apoptosis. A rigorous test of the hypothesis remains to be undertaken, but would require a direct manipulation of the rate of mtDNA mutagenesis, to test whether this could alter the kinetics of aging.     

The euryarchaeotes, a subdomain of Archaea, survive on a single DNA polymerase: fact or farce?

Archaea is now recognized as the third domain of life. Since their discovery, much effort has been directed towards understanding the molecular biology and biochemistry of Archaea. The objective is to comprehend the complete structure and the depth of the phylogenetic tree of life. DNA replication is one of the most important events in living organisms and DNA polymerase is the key enzyme in the molecular machinery which drives the process. All archaeal DNA polymerases were thought to belong to family B. This was because all of the products of pol genes that had been cloned showed amino acid sequence similarities to those of this family, which includes three eukaryal DNA replicases and Escherichia coli DNA polymerase II. Recently, we found a new heterodimeric DNA polymerase from the hyperthermophilic archaeon, Pyrococcus furiosus. The genes coding for the subunits of this DNA polymerase are conserved in the euryarchaeotes whose genomes have been completely sequenced. The biochemical characteristics of the novel DNA polymerase family suggest that its members play an important role in DNA replication within euryarchaeal cells. We review here our current knowledge on DNA polymerases in Archaea with emphasis on the novel DNA polymerase discovered in Euryarchaeota.     

What cost mitochondria? The maintenance of functional mitochondrial DNA within and across generations

The peculiar biology of mitochondrial DNA (mtDNA) potentially has detrimental consequences for organismal health and lifespan. Typically, eukaryotic cells contain multiple mitochondria, each with multiple mtDNA genomes. The high copy number of mtDNA implies that selection on mtDNA functionality is relaxed. Furthermore, because mtDNA replication is not strictly regulated, within-cell selection may favour mtDNA variants with a replication advantage, but a deleterious effect on cell fitness. The opportunities for selfish mtDNA mutations to spread are restricted by various organism-level adaptations, such as uniparental transmission, germline mtDNA bottlenecks, germline selection and, during somatic growth, regular alternation between fusion and fission of mitochondria. These mechanisms are all hypothesized to maintain functional mtDNA. However, the strength of selection for maintenance of functional mtDNA progressively declines with age, resulting in age-related diseases. Furthermore, organismal adaptations that most probably evolved to restrict the opportunities for selfish mtDNA create secondary problems. Owing to predominantly maternal mtDNA transmission, recombination among mtDNA from different individuals is highly restricted or absent, reducing the scope for repair. Moreover, maternal inheritance precludes selection against mtDNA variants with male-specific effects. We finish by discussing the consequences of life-history differences among taxa with respect to mtDNA evolution and make a case for the use of microorganisms to experimentally manipulate levels of selection.     

Convergent evolution of gigantism in damselflies of Africa and South America? Evidence from nuclear and mitochondrial sequence data

Extreme large body size is rare in modern Zygoptera (damselflies). Only the South and Central American damselfly family Pseudostigmatidae and one African species, Coryphagrion grandis, share the morphological trait of gigantism. By means of phylogenetic analyses using two mitochondrial markers (16S rDNA and ND1) and one nuclear marker (EF1) in combination with an existing morphological data set, we trace the evolution of gigantism in damselflies. Individual and combined data sets were analyzed using the maximum parsimony, minimum evolution and maximum likelihood algorithms. Regardless of the algorithm used and the data set analyzed all principal tree topologies support a monophyly of the damselfly taxa displaying giant body size. This supports the view that the evolution of gigantism in damselflies from Africa and South America is not the result of convergent evolution due to strikingly similar habitat preferences, but rather the result of close genealogical relationship. Because modern odonates evolved before the split of Africa from Gondwanaland, the proposed phylogeny suggests that C. grandis represents a Gondwana relict.     

Is Physiological Performance a Good Predictor for Fitness? Insights from an Invasive Plant Species

Is physiological performance a suitable proxy of fitness in plants? Although, several studies have been conducted to measure some fitness-related traits and physiological performance, direct assessments are seldom found in the literature. Here, we assessed the physiology-fitness relationship using second-generation individuals of the invasive plant species Taraxacum officinale from 17 localities distributed in five continents. Specifically, we tested if i) the maximum quantum yield is a good predictor for seed-output ii) whether this physiology-fitness relationship can be modified by environmental heterogeneity, and iii) if this relationship has an adaptive consequence for T. officinale individuals from different localities. Overall, we found a significant positive relationship between the maximum quantum yield and fitness for all localities evaluated, but this relationship decreased in T. officinale individuals from localities with greater environmental heterogeneity. Finally, we found that those individuals from localities where environmental conditions are highly seasonal performed better under heterogeneous environmental conditions. Contrarily, under homogeneous controlled conditions, those individuals from localities with low environmental seasonality performed much better. In conclusion, our results suggest that the maximum quantum yield seem to be good predictors for plant fitness. We suggest that rapid measurements, such as those obtained from the maximum quantum yield, could provide a straightforward proxy of individual’s fitness in changing environments.     

Design, synthesis, and evaluation of an α-tocopherol analogue as a mitochondrial antioxidant

An efficient synthesis has provided access to a novel α-tocopherol analogue (2), as well as its trifluoroacetate salt and acetate ester. An annulation reaction was used to establish the pyridinol core structure and a Stille coupling reaction was employed for conjugation with the tocopherol side chain. This analogue was shown to suppress the levels of reactive oxygen species in cultured cells, and to quench peroxidation of mitochondrial membranes.     

The nuclear protein HMGB1, a new kind of chemokine?

The chromosomal protein HMGB1 is now regarded as a proinflammatory cytokine. Importantly, HMGB1 has chemotactic activity suggesting its involvement in the early and late events of the inflammatory reaction. Therefore, HMGB1 has all the hallmarks of a chemokine (chemotactic cytokine). We propose to classify HMGB1 into a new group of proteins unrelated structurally to chemokines but having chemokine-like functions, and to name this class CLF (chemokine-like functions). The CLF class should include other unrelated molecules such as urokinase and its receptor, cytokines macrophage migration inhibitory factor (MIF) and interleukin (IL)-6, anaphylatoxin C5a, ribosomal protein S19, and thioredoxin that have similar chemokine-like activities. This innovative concept may lead to the identification of new therapeutic targets.