Mitochondrial genomes represent relict bacterial genomes derived from a progenitor α‐proteobacterium that gave rise to all mitochondria through an ancient endosymbiosis. Evolution has massively reduced these genomes, yet despite relative simplicity their organization and expression has developed considerable novelty throughout eukaryotic evolution. Few organisms have reengineered their mitochondrial genomes as thoroughly as the protist lineage of dinoflagellates. Recent work reveals dinoflagellate mitochondrial genomes as likely the most gene‐impoverished of any free‐living eukaryote, encoding only two to three proteins. (...) The organization and expression of these genomes, however, is far from the simplicity their gene content would suggest. Gene duplication, fragmentation, and scrambling have resulted in an inflated and complex genome organization. Extensive RNA editing then recodes gene transcripts, and trans‐splicing is required to assemble full‐length transcripts for at least one fragmented gene. Even after these processes, messenger RNAs (mRNAs) lack canonical start codons and most transcripts have abandoned stop codons altogether. (shrink)

We review a recent paper in Genome Research by Guantes et al. showing that nuclear gene expression is influenced by the bioenergetic status of the mitochondria. The amount of energy that mitochondria make available for gene expression varies considerably. It depends on: the energetic demands of the tissue; the mitochondrial DNA (mtDNA) mutant load; the number of mitochondria; stressors present in the cell. Hence, when failing mitochondria place the cell in energy crisis there are major effects on gene expression (...) affecting the risk of degenerative diseases, cancer and ageing. In 2015 the UK parliament approved a change in the regulation of IVF techniques, allowing “Mitochondrial replacement therapy” to become a reproductive choice for women at risk of transmitting mitochondrial disease to their children. This is the first time that this technique will be available. Therefore understanding the interaction between mitochondria and the nucleus has never been more important. (shrink)

This manuscript reviews recent evidence supporting the utility of telomeres and mitochondrial DNA copy number (mtDNAcn) in detecting the biological impacts of adverse childhood experiences (ACEs) and outlines mechanisms that may mediate the connection between early stress and poor physical and mental health. Critical to interrupting the health sequelae of ACEs such as abuse, neglect, and neighborhood disorder, is the discovery of biomarkers of risk and resilience. The molecular markers of chronic stress exposure, telomere length and mtDNAcn, represent critical (...) biological links between ACEs and poor health outcomes. We examine how telomeres and mtDNAcn may exacerbate health disparities and contribute to the intergenerational transmission of trauma. Finally, we explore how these molecular markers of early stress exposure may help define the role of resilience and develop effective interventions to moderate ACE health risk impact. (shrink)

Developing models of biological mechanisms, such as those involved in respiration in cells, often requires collaborative effort drawing upon techniques developed and information generated in different disciplines. Biochemists in the early decades of the 20th century uncovered all but the most elusive chemical operations involved in cellular respiration, but were unable to align the reaction pathways with particular structures in the cell. During the period 1940-1965 cell biology was emerging as a new discipline and made distinctive contributions to understanding (...) the role of the mitochondrion and its component parts in cellular respiration. In particular, by developing techniques for localizing enzymes or enzyme systems in specific cellular components, cell biologists provided crucial information about the organized structures in which the biochemical reactions occurred. Although the idea that biochemical operations are intimately related to and depend on cell structures was at odds with the then-dominant emphasis on systems of soluble enzymes in biochemistry, a reconceptualization of energetic processes in the 1960s and 1970s made it clear why cell structure was critical to the biochemical account. This paper examines how numerous excursions between biochemistry and cell biology contributed a new understanding of the mechanism of cellular respiration. (shrink)

In February 2015 the UK became the first country to legalise high-profile mitochondrial replacement techniques, which involve the creation of offspring using genetic material from three individuals. The aim of these new cell reconstruction techniques is to prevent the transmission of maternally inherited mitochondrial disorders to biological offspring. During the UK debates, MRTs were often positioned as a straightforward and unique solution for the ‘eradication’ of mitochondrial disorders, enabling hundreds of women to have a healthy, biologically-related child. (...) However, many questions regarding future applications and potential users remain. Drawing on a current qualitative study on reproductive choices in the context of mitochondrial disorders, this article illustrates how the potential limitations of MRTs have been obscured in public debates by contrasting the claims made about the future beneficiaries with insights from families affected by mitochondrial disorders and medical experts. The analysis illuminates the complex choices with which families and individuals affected by mitochondrial disorders are faced, which have thus far remained invisible. An argument is presented for improved information for the public as well as an intensification of critical empirical research around the complex and specific needs of future beneficiaries of new reproductive biotechnologies. (shrink)

Protein translocation across biological membranes is of fundamental importance for the biogenesis of organelles and in protein secretion. We will give an overview of the recent achievements in the understanding of protein translocation across mitochondrial membranes(1‐5). In particular we will focus on recently identified components of the mitochondrial import apparatus.

In the 1950s and 1960s, the search for the mechanism of oxidative phosphorylation by biochemists paralleled the description of mitochondrial form by George Palade and Fritiof Sjöstrand using electron microscopy. This paper explores the extent to which biochemists studying oxidative phosphorylation took mitochondrial form into account in the formulation of hypotheses, design of experiments, and interpretation of results. By examining experimental approaches employed by the biochemists studying oxidative phosphorylation, and their interactions with Palade, I suggest that use of (...) mitochondrial form as a guide to experimentation and interpretation varied considerably among investigators. Most notably, Peter Mitchell, whose chemiosmotic hypothesis was ultimately the basis of the correct mechanism of oxidative phosphorylation, incorporated crucial aspects of mitochondrial form into his model that others failed to recognize. I discuss these historical observations in terms of the background and training of the biochemists, as well as a proposed heuristic of form, whose use may increase the possibility that biologically meaningful molecular mechanisms will be discovered. (shrink)

Hypoxia hampers ATP production and threatens cell survival. Since cellular energetics tightly controls cell responses and fate, ATP levels and dynamics are of utmost importance. An integrated mathematical model of ATP synthesis by the mitochondrial oxidative phosphorylation/electron transfer chain system has been recently published :e36, 2005). This model was validated under static conditions. To evaluate its performance under dynamical situations, we implemented and simulated it . Inner membrane potential and [NADH] were used as indicators of mitochondrial function. Root (...) mean squared error was used to compare simulations and experiments :39155–39165, 2003). Steady-state experimental data were reproduced within 2–6%. Model dynamics were evaluated under: baseline, activation of NADH production, addition of ADP, addition of inorganic phosphate, oxygen exhaustion. In all phases, except the last one, ΔΨ and [NADH] as well as oxygen consumption, were reproduced . Under anoxia, simulated ΔΨ markedly depolarized . In conclusion, the model reproduces dynamic data as long as oxygen is present. Anticipated improvement by the inclusion of ATP consumption and explicit Krebs cycle are under evaluation. (shrink)

While its mechanism and biological significance are unknown, the utility of a short mitochondrial DNA sequence as a “barcode” providing accurate species identification has revolutionized the classification of organisms. Since highest accuracy was achieved with recently diverged species, hopes were raised that barcodes would throw light on the speciation process. Indeed, a failure of a maternally donated, rapidly mutating, mitochondrial genome to coadapt its gene products with those of a paternally donated nuclear genome could result in developmental failure, (...) thus creating a post-zygotic barrier leading to reproductive isolation and sympatric branching into independent species. However, the barcode itself encodes a highly conserved, species-invariant, protein, and the discriminatory power resides in the non-amino acid specific bases of synonymous codons. It is here shown how the latter could register changes in the oligonucleotide frequencies of nuclear DNA that, when they fail to match in pairing meiotic chromosomes, could reproductively isolate the parents so launching a primary divergence into two species. It is proposed that, while not itself contributing to speciation, the barcode sequence provides an index of the nuclear DNA oligonucleotide frequencies that drive speciation. (shrink)

Mitochondria can change their shape from discrete isolated organelles to a large continuous reticulum. The cellular advantages underlying these fused networks are still incompletely understood. In this paper, we describe and compare hypotheses regarding the function of mitochondrial networks. We use mathematical and physical tools both to investigate existing hypotheses and to generate new ones, and we suggest experimental and modelling strategies. Among the novel insights we underline from this work are the possibilities that (i) selective mitophagy is not (...) required for quality control because selective fusion is sufficient; (ii) increased connectivity may have non‐linear effects on the diffusion rate of proteins; and (iii) fused networks can act to dampen biochemical fluctuations. We hope to convey to the reader that quantitative approaches can drive advances in the understanding of the physiological advantage of these morphological changes. (shrink)

What’s the basis for considering an egg donor a genetic parent but not a mitochondrial donor? I will argue that a closer look at the biological facts will not give us an answer to this question because the process by which one becomes a genetic parent, i.e., the process of reproduction, is not a concept that can be settled by looking. It is, rather, a concept in need of philosophical attention. The details of my argument will rest on recent (...) developments in biological technology, but the persuasiveness of my argument will turn on the history of another biological concept, death. Given some important similarities between the two concepts, the way in which ‘death’ evolved in the recent past can provide guidance on how we should think about ‘reproduction.’. (shrink)

The proliferation of mitochondrial DNA (mtDNA) with deletion mutations has been linked to aging and age related neurodegenerative conditions. In this study we model the effect of mtDNA half-life on mtDNA competition and selection. It has been proposed that mutation deletions (mtDNAdel\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{del}$$\end{document}) have a replicative advantage over wild-type (mtDNAwild\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{wild}$$\end{document}) and that this is detrimental to the host cell, especially in (...) post-mitotic cells. An individual cell can be viewed as forming a closed ecosystem containing a large population of independently replicating mtDNA. Within this enclosed environment a selfishly replicating mtDNAdel\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{del}$$\end{document} would compete with the mtDNAwild\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{wild}$$\end{document} for space and resources to the detriment of the host cell. In this paper, we use a computer simulation to model cell survival in an environment where mtDNAwild\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{wild}$$\end{document} compete with mtDNAdel\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{del}$$\end{document} such that the cell expires upon mtDNAwild\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{wild}$$\end{document} extinction. We focus on the survival time for long lived post-mitotic cells, such as neurons. We confirm previous observations that mtDNAdel\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{del}$$\end{document} do have a replicative advantage over mtDNAwild\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{wild}$$\end{document}. As expected, cell survival times diminished with increased mutation probabilities, however, the relationship between survival time and mutation rate was non-linear, that is, a ten-fold increase in mutation probability only halved the survival time. The results of our model also showed that a modest increase in half-life had a profound affect on extending cell survival time, thereby, mitigating the replicative advantage of mtDNAdel\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{del}$$\end{document}. Given the relevance of mitochondrial dysfunction to various neurodegenerative conditions, we propose that therapies to increase mtDNA half-life could significantly delay their onset. (shrink)

No overarching hypotheses tie the basic mechanisms of mitochondrial reactive oxygen species (ROS) production to activity dependent synapse pruning—a fundamental biological process in health and disease. Neuronal activity divergently regulates mitochondrial ROS: activity decreases whereas inactivity increases their production, respectively. Placing mitochondrial ROS as innate synaptic activity sentinels informs the novel hypothesis that: (1) at an inactive synapse, increased mitochondrial ROS production initiates intrinsic apoptosis dependent pruning; and (2) at an active synapse, decreased mitochondrial ROS (...) production masks intrinsic apoptosis dependent pruning. Immature antioxidant defense may enable the developing brain to harness mitochondrial ROS to prune weak synapses. Beyond development, endogenous antioxidant defense constrains mitochondrial (ROS) to mask pruning. Unwanted age‐related synapse loss may arise when mitochondrial ROS aberrantly recapitulate developmental pruning. Placing mitochondrial ROS with their hands on the shears is beneficial in early but deleterious in later life. (shrink)

The chronologic age classically used in demography is often unable to give useful information about which exact stage in development or aging processes has reached an organism. Hence, we propose here to explain in some applications for what reason the chronologic age fails in explaining totally the observed state of an organism, which leads to propose a new notion, the biological age. This biological age is essentially determined by the number of divisions before the Hayflick’s limit the tissue or mitochondrion (...) in a critical organ (in the sense where its loss causes the death of the whole organism) has already used for its development and adult phases. We give a precise definition of the biological age of an organ based on the Hayflick’s limit of its cells and we introduce a desynchronization index (the cell entropy) for some critical tissues or membranes, which are mainly skin, intestinal endothelium, alveoli epithelium and mitochondrial inner membrane. In these actively metabolising interface tissues or membranes, there is a rapid turnover of cells, of their cytoplasmic constituents such as proteins, and of membrane lipids. The boundaries corresponding to these tissues, cells or membranes have vital functions of interface with the environment (protection, homeothermy, nutrition and respiration) and have a rapid turnover (the total cell renewal time is in mice equal to 3 weeks for the skin, 1.5 day for the intestine, 4 months for the alveolae and 11 days for mitochondrial inner membrane) conditioning their biological age. The biological age of a tissue is made of two major components: (1) first, its embryonic age based on the distance (in number of divisions) between the birth date of its first differentiated cell and the time until it reaches its final boundary at the end of its development and (2) second, its adult age whose complement until its death is just the lapse of time made of the sum of remaining cell cycle durations authorized by its Hayflick’s limit. From this definition, we calculate the global biological lifespan of an organism and revisit notions like demographic survival curves, duration and synchrony of cell cycles, living boundaries from proto-cells to organs, and embryonic and adult phases duration. (shrink)

A cell contains many copies of mitochondrial DNA. The distribution of a mitochondrial gene mutation in a cell culture is governed by the way in which the mtDNA molecules of a cell are replicated and partitioned between the two daughter cells during mitosis. Assuming that this partition process is random, we describe the evolution of the mitochondrial genetic state of a cell culture. The mutated mtDNA is ultimately segregated and the rate of the trend to segregation is (...) relatively slow. It is nevertheless greatly accelerated if the model takes into account the spatial mtDNA partition by the mitochondrial compartments. (shrink)

In angiosperms cytoplasmic DNA is typically passed on maternally through ovules. Genes in the mtDNA may cause male sterility. When male-sterile (female) cytotypes produce more seeds than cosexuals, they pass on more copies of their mtDNA and will co-occur with cosexuals with a neutral cytotype. Cytoplasmic gynodioecy is a well-known phenomenon in angiosperms, both in wild and crop plants. In some conifer families (e.g. Pinaceae) mitochondria are also maternally inherited. However in some other families (e.g. Taxaceae and Cupressaceae) mtDNA is (...) paternally inherited through the pollen. With paternal mtDNA inheritance, male cytotypes that produce more pollen than cosexuals are expected to co-occur with cosexuals. This is uncharted territory. An ESS model shows that the presence of male cytotypes selects for more female allocation in the cosexual, i.e. for sexual specialisation. An allele that switches sex from male to female can then invade. This leads to rapid loss of the neutral cytotype of the cosexual, fixation of the male cytotype and dioecy with 50% males and 50% females. The models suggest that paternal inheritance of mtDNA facilitates the evolution dioecy. Consistent with this hypothesis the Pinaceae are 100% monoecious, while dioecy is common in the Taxaceae family and in the genus Juniperus (Cupressaceae). However, no reliable data are yet available on both mode of inheritance of mtDNA and gender variation of the same species. When cosexuals benefit from reproductive assurance (high selfing rate, low inbreeding depression, low fertilisation) they maintain themselves next to males and females. This predicted pattern with three sex types present in the same population is observed in conifers in nature. (shrink)

Previous studies have shown that zinc deficiency leads to apoptosis of neuronal precursor cells in vivo and in vitro. In addition to the role of p53 as a nuclear transcription factor in zinc deficient cultured human neuronal precursors (NT-2), we have now identified the translocation of phosphorylated p53 to the mitochondria and p53-dependent increases in the pro-apoptotic mitochondrial protein BAX leading to a loss of mitochondrial membrane potential as demonstrated by a 25% decrease in JC-1 red:green fluorescence ratio. (...) Disruption of mitochondrial membrane integrity was accompanied by efflux of the apoptosis inducing factor (AIF) from the mitochondria and translocation to the nucleus with a significant increase in reactive oxygen species (ROS) after 24 h of zinc deficiency. Measurement of caspase cleavage, mRNA, and treatment with caspase inhibitors revealed the involvement of caspases 2, 3, 6, and 7 in zinc deficiency-mediated apoptosis. Down-stream targets of caspase activation, including the nuclear structure protein lamin and polyADP ribose polymerase (PARP), which participates in DNA repair, were also cleaved. Transfection with a dominant-negative p53 construct and use of the p53 inhibitor, pifithrin- ␮, established that these alterations were largely dependent on p53. Together these data identify a cascade of events involving mitochondrial p53 as well as p53-dependent caspase-mediated mechanisms leading to apoptosis during zinc deficiency. (shrink)

Where do we come from? Is our destiny determined by the genes we inherit? Do we all see the same blue color when we look at the sky? In this book Gottfried (Jeff) Schatz, the world-renowned biochemist and co-discoverer of mitochondrial DNA, gives lucid - albeit often surprising - answers to universal questions and takes the reader on a fascinating journey of discovery across the boundaries of scientific disciplines. With passion and a keen sense of wonder, he draws on (...) philosophy, cultural history and art to formulate his reflections on the mystery of life. The key to understanding life is to be found in its chemistry, and he proves that this is no dry endeavor and certainly not devoid of beauty. The result is a collection of eloquently and poetically written essays dealing with key issues in the natural sciences. It will appeal not only to scientists, but to all curious minds, regardless of educational and professional background. (shrink)

Ever since their introduction a decade ago, stable introns, a type of noncoding (nc)RNAs, are found to be key players in different important cellular processes acting through regulation of gene expression and feedback loops to maintain cellular homeostasis. Despite being commonly regarded as useless byproducts, recent studies in yeast suggested that stable introns are essential for cell survivability under starvation. In Drosophila, we found that a stable intron, sisR‐1, has a direct effect in regulating mitochondrial dynamics during short‐term fasting (...) and subsequently improved overall oocyte quality. We speculated that the beneficial effects implicated by sisR‐1 is through the activation of mitohormesis, an interesting phenomenon in mitochondrial biology. Mitohormesis is suggested to improve health span and lifespan of cells and organisms, but the involvement of ncRNAs is not well‐documented. Here, we discuss the potential role of sisR‐1 and other ncRNAs in activating mitohormesis and the possible applications in improving cellular and organismal health. (shrink)

We use genomic information to tell us stories of evolutionary origins. But what does it mean when different genomes report wildly different accounts of lineage history? This genomic “discordance” can be a consequence of a fascinating suite of natural history and evolutionary phenomena, from the different inheritance mechanisms of nuclear versus cytoplasmic (mitochondrial and plastid) genomes to hybridization and introgression to horizontal transfer. Here, we explore how we can use these distinct genomic stories to provide new insights into the (...) maintenance of sexual reproduction, one of the most important unanswered questions in biology. We focus on the strikingly distinct nuclear versus mitochondrial versions of the story surrounding the origin and maintenance of asexual lineages in Potamopyrgus antipodarum, a New Zealand freshwater snail. While key questions remain unresolved, these data inspire multiple testable hypotheses that can be powerfully applied across a broad range of taxa toward a deeper understanding of the causes and consequences of mitonuclear discordance, the maintenance of sex, and the origin of new asexual lineages. (shrink)

With the recent report of a live birth after use of Mitochondrial replacement therapy, sometimes called ‘Three-parent IVF’, the clinical application of the technique is fast becoming a reality. While the United Kingdom allows the procedure under regulatory scrutiny, it remains effectively outlawed in many other countries. We argue that such prohibitions may violate individuals’ procreative rights, grounded in individuals’ interest in genetic affinity. The interest in genetic affinity was recently endorsed by Singapore’s highest court, reflecting an emphasis on (...) the importance of biological ties found across the globe. We apply that reasoning to make the case for a right to ‘Three-parent IVF’. (shrink)

Assisted reproduction often involves biological contributions by third parties such as egg/sperm donors, mitochondrial DNA donors, and surrogate mothers. However, these arrangements are also characterised by a biological relationship between the child and at least one intending parent. For example, one or both intending parents might use their own eggs/sperm in surrogacy, or an intending mother might conceive using donor sperm or gestate a donor embryo. What happens when this relationship is absent, as in the case of 'double‐donor surrogacy' (...) arrangements (DDS)? Here, a child is conceived using both donor eggs and sperm, carried by a surrogate, and raised by the commissioning parents. In this paper, I critically examine proposals to allow DDS in the United Kingdom, and the intentionalist justification for treating this practice distinctly (morally and legally speaking) from private adoption. I argue that the intentionalist approach cannot plausibly justify such a distinction and that other approaches to moral parenthood are also unlikely to succeed. (shrink)

Recently, constructive neutral evolution has been touted as an important concept for the understanding of the emergence of cellular complexity. It has been invoked to help explain the development and retention of, amongst others, RNA splicing, RNA editing and ribosomal and mitochondrial respiratory chain complexity. The theory originated as a welcome explanation of isolated small scale cellular idiosyncrasies and as a reaction to ‘overselectionism’. Here I contend, that in its extended form, it has major conceptual problems, can not explain (...) observed patterns of complex processes, is too easily dismissive of alternative selectionist models, underestimates the creative force of complexity as such, and – if seen as a major evolutionary mechanism for all organisms – could stifle further thought regarding the evolution of highly complex biological processes. (shrink)

Interpreting John Paul II's message to the Pontifical Academy of Sciences in the context of the new scientific discoveries concerning the mitochondrial DNA, one can argue that the human species emerged in Africa some 200,000 years ago. The very problem of the emergence of the human soul in the process of biological evolution represents a subject outside the cognitive competence of science. Attempts can be undertaken to explain this issue in the epistemological perspective of philosophy and theology. In traditional (...) versions of evolutionary theism, God* s interaction in nature was interpreted in causal categories when deterministic dependences were stressed in the process of evolutionary growth. In new proposals, God's presence in an evolving nature has been explained in categories of potentialities and propensities built by God into an evolving Nature. Consequently, in this approach God could be conceived not as a Paleyan designer but rather as a composer unfolding the possibilities hidden in His creation. The future of the evolutionary process depends not only on cosmic physical determinants; it depends to a large extent on the quality of cooperation of human actions with the influence of the Divine Creator. Accordingly, the shape of human culture, as well as the state of moral consciousness of Homo sapiens, should be taken into consideration to discuss the future evolution of the human species. /// Interpretando a mensagem do Papa João Paulo II à Academia Pontifícia das Ciências no contexto das novas descobertas científicas referentes ao DNA mitocondrial, o autor do artigo considera ser possível defender que a espécie humana surgiu em África há cerca de 200 000 anos. Mas o problema da emergência da alma humana no contexto do processo da evolução biológica representa um assunto que está fora da competência cognitiva da ciência. Contudo é possível realizar tentativas no sentido de explicar esta questão na perspectiva epistemológica da filosofia e da teologia. Nas versões tradicionais do teísmo evolutivo, a interacção de Deus com a natureza era interpretada segundo categorias causais quando as dependências deterministicas eram sublinhadas no processo do desenvolvimento evolutivo. No contexto de novas propostas interpretativas, a presença de Deus na ordem evolutiva tem sido explicada em termos das potencialidades e das propensidades induzidas por Deus na Natureza em evolução. Consequentemente, segundo esta abordagem Deus poderia ser concebido não como sábio projectista de que fala William Paley, mas antes como um compositor fazendo vir ao de cima as possibilidades escondidas na sua própria criação. O futuro do processo evolutivo depende não apenas das determinantes físicas do cosmos; ele depende em larga medida da qualidade da cooperação das acções humanas com a influência do Criador. Neste sentido, o artigo defende que a forma da cultura humana, bem como o estado da consciência moral do homo sapiens deve ser tido em consideração em ordem a se poder discutir a evolução futura da espécie humana. (shrink)

Despite 250 years of work in systematics, the majority of species remains to be identified. Rising extinction rates and the need for increased biological monitoring lend urgency to this task. DNA sequencing, with key sequences serving as a “barcode”, has therefore been proposed as a technology that might expedite species identification. In particular, the mitochondrial cytochrome c oxidase subunit 1 gene has been employed as a possible DNA marker for species and a number of studies in a variety of (...) taxa have accordingly been carried out to examine its efficacy. In general, these studies demonstrate that DNA barcoding resolves most species, although some taxa have proved intractable. In some studies, barcoding provided a means of highlighting potential cryptic, synonymous or extinct species as well as matching adults with immature specimens. Higher taxa, however, have not been resolved as accurately as species. Nonetheless, DNA barcoding appears to offer a means of identifying species and may become a standard tool. BioEssays 29: 188–197, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Researchers who propose projects about the human past frequently fail to distinguish between scientific value and the impact of both the proposal and the possible outcome for participant groups. It is only in recent years, and still in relatively few cases, that Aboriginal Australians have been directly involved in projects about themselves. The legacy of previous research experiences is a lingering distrust of ‘white’ researchers who visit communities briefly, take material/information, publish papers, and are rarely seen again. This distrust is (...) understandable but in turn becomes a barrier which many well-intentioned researchers are unable or unwilling to overcome. The expectations of the scientific community, particularly in the field of molecular biology, simply do not make allowances in terms of time or funding to build a trusting relationship between the researchers and the researched.Sensitivity to indigenous rights and expectations with regard to scientific research brings obligations to scientific investigators with which few are well prepared to deal. The direct involvement of indigenous people in research about themselves is essential to the development of trusting working relationships likely to result in valuable outcomes for all participants and increased opportunities for ongoing research.Well negotiated, co-operative research can provide information of value to both scientific investigators and local participants, but adequate and ongoing consultation, as well as the return of results to the communities in an accurate and appropriate form must be part of research strategy. For example, information about mitochondrial DNA studies may assist Indigenous Australian people, whose families were dispersed during colonisation by Europeans, to trace links with the past, find ‘stolen children’ and by association with other anthropological, linguistic and archaeological data, repossess some remnants of traditional knowledge, but researchers must ensure that participants have a realistic understanding of the limitations of the research. (shrink)

This essay considers biotrophic cyst and root‐knot nematodes in relation to their biology, host–parasite interactions and molecular genetics. These nematodes have to face the biological consequences of the physical constraints imposed by the soil environment in which they live while their hosts inhabit both above and below ground environments. The two groups of nematodes appear to have adopted radically different solutions to these problems with the result that one group is a host specialist and reproduces sexually while the other (...) has an enormous host range and reproduces by mitotic parthenogenesis. We consider what is known about the modes of parasitism used by these nematodes and how it relates to their host range, including the surprising finding that parasitism genes in both nematode groups have been recruited from bacteria. The nuclear and mitochondrial genomes of these two nematode groups are very different and we consider how these findings relate to the biology of the organisms. BioEssays 30:249–259, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

We present the first comprehensive taxonomic revision and review the biology of the olingos, the endemic Neotropical procyonid genus Bassaricyon, based on most specimens available in museums, and with data derived from anatomy, morphometrics, mitochondrial and nuclear DNA, field observations, and geographic range modeling. Species of Bassaricyon are primarily forest-living, arboreal, nocturnal, frugivorous, and solitary, and have one young at a time. We demonstrate that four olingo species can be recognized, including a Central American species (Bassaricyon gabbii), lowland (...) species with eastern, cis-Andean (Bassaricyon alleni) and western, trans-Andean (Bassaricyon medius) distributions, and a species endemic to cloud forests in the Andes. The oldest evolutionary divergence in the genus is between this last species, endemic to the Andes of Colombia and Ecuador, and all other species, which occur in lower elevation habitats. Surprisingly, this Andean endemic species, which we call the Olinguito, has never been previously described; it represents a new species in the order Carnivora and is the smallest living member of the family Procyonidae. We report on the biology of this new species based on information from museum specimens, niche modeling, and fieldwork in western Ecuador, and describe four Olinguito subspecies based on morphological distinctions across different regions of the Northern Andes. (shrink)

Citrate, an organic trivalent anion, is a major substrate for generation of energy in most cells. It is produced in mitochondria and used either in the Krebs' cycle or released into cytoplasm through a specific mitochondrial carriers. Citrate can also be taken up from blood through different plasma membrane transporters. In the cytoplasm, citrate can be used ultimately for fatty acid synthesis, which is increased in cancer cells. Here, we review the ways in which citrate can be transported and (...) discuss the changes in transport and metabolism that occur in cancer cells. The primary focus is on the prostate gland, which is known to produce and release large amounts of citrate during its normal secretory function. The significant changes that occur in citrate‐related metabolism and transport in prostate cancer are the second focus. This review strives to relate these mechanisms to molecular biology on the one hand and to clinical applications on the other. (shrink)

Recent research has pointed to the importance of the prenatal environment in the etiology of autism spectrum disorder (ASD) but the biological mechanisms which mitigate these environmental factors are not clear. Mitochondrial metabolism abnormalities, inflammation and oxidative stress as common physiological disturbances associated with ASD. Network analysis of the scientific literature identified several leading prenatal environmental factors associated with ASD, particularly air pollution, pesticides, the microbiome and epigenetics. These leading prenatal environmental factors were found to be most associated with (...) inflammation, followed by oxidative stress and mitochondrial dysfunction. Other prenatal factors associated with ASD not identified by the network analysis were also found to be significantly associated with these common physiological disturbances. A better understanding of the biological mechanism which mediate the effect of prenatal environmental factors can lead to insights of how ASD develops and the development of targeted therapeutics to prevent ASD from occuring. (shrink)

The origin of the eukaryotic cell nucleus and the selective forces that drove its evolution remain unknown and are a matter of controversy. Autogenous models state that both the nucleus and endoplasmic reticulum (ER) derived from the invagination of the plasma membrane, but most of them do not advance clear selective forces for this process. Alternative models proposing an endosymbiotic origin of the nucleus fail to provide a pathway fully compatible with our knowledge of cell biology. We propose here (...) an evolutionary scenario that reconciles both an ancestral endosymbiotic origin of the eukaryotic nucleus (endosymbiosis of a methanogenic archaeon within a fermentative myxobacterium) with an autogenous generation of the contemporary nuclear membrane and ER from the bacterial membrane. We specifically state two selective forces that operated sequentially during its evolution: (1) metabolic compartmentation to avoid deleterious co‐existence of anabolic (autotrophic synthesis by the methanogen) and catabolic (fermentation by the myxobacterium) pathways in the cell, and (2) avoidance of aberrant protein synthesis due to intron spreading in the ancient archaeal genome following mitochondrial acquisition and loss of methanogenesis. BioEssays 28: 525–533, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

The advantages and risks of a number of new genome modifying procedures seeking to create healthy or enhanced individuals, such as Maternal Spindle Transfer, Pronuclear Transfer, Cytoplasmic Transfer and Genome Editing, are currently being assessed from an ethical perspective, by national and international policy organizations. One important aspect being examined concerns the effects of these procedures on different kinds of identity. In other words, whether or not a procedure only modifies the qualities or properties of an existing human being, meaning (...) that merely the qualitative identity of this single individual is affected, or whether a procedure results in the creation of a new individual, meaning that a numerically distinct human being would have come into existence. In this article, the different identity arguments proposed, so far, are presented with respect to these novel reproductive procedures. An alternative view is then developed using the Origin Essentialism argument to indicate that any change in the creative conditions of an individual such as in his or her biology but also the moment in time, and the three dimensions of space, will have a numerical identity effect and bring into existence a new individual who would not, otherwise, have existed. Because of this, it is concluded that a form of selection may have taken place in which a preference was expressed for one new possible individual instead of another, based on some frame of reference. This may then mean that a selection between persons has occured contravening the European Union Charter of Fundamental Rights which was ratified in 2000. (shrink)

The Arf family proteins are best known for their roles in the vesicle biogenesis. However, they also play fundamental roles in a wide range of cellular regulation besides vesicular trafficking, such as modulation of lipid metabolic enzymes, cytoskeleton remodeling, ciliogenesis, lysosomal, and mitochondrial morphology and functions. Growing studies continue to expand the downstream effector landscape of Arf proteins, especially for the less‐studied members, revealing new biological functions, such as amino acid sensing. Experiments with cutting‐edge technologies and in vivo functional (...) studies in the last decade help to provide a more comprehensive view of Arf family functions. In this review, we summarize the cellular functions that are regulated by at least two different Arf members with an emphasis on those beyond vesicle biogenesis. (shrink)

What does it mean that humans were not the only hominin? Or, more importantly, what does it mean that other hominins held cultural, biological, and perhaps even linguistic equivalence to human beings? Drawing on mitochondrial DNA analyses, theories of deep history, and attention to the inhuman, this essay argues that such equivalence entails not only the reality of human/nonhuman genetic compatibility but the existence of politics in places and times without humans. Such a politics of non-humans would entail political (...) and social forms playing a central role in the development of humanity. If politico-social experiences in the prehuman and non-human hominin communities actually affected behavior and practices, then the development of humanity is an effect of politics rather than a precondition for it. (shrink)

A flurry of recent publications have challenged consensus views on the tempo and mode of plastid (chloroplast) evolution in eukaryotes and, more generally, the impact of endosymbiosis in the evolution of the nuclear genome. Endosymbiont‐to‐nucleus gene transfer is an essential component of the transition from endosymbiont to organelle, but the sheer diversity of algal‐derived genes in photosynthetic organisms such as diatoms, as well as the existence of genes of putative plastid ancestry in the nuclear genomes of plastid‐lacking eukaryotes such as (...) ciliates and choanoflagellates, defy simple explanation. Collectively, these papers underscore the power of comparative genomics and, at the same time, reveal how little we know with certainty about the earliest stages of the evolution of photosynthetic eukaryotes. Editor's suggested further reading in BioEssaysEarly steps in plastid evolution: current ideas and controversies AbstractDinoflagellate mitochondrial genomes: stretching the rules of molecular biology Abstract. (shrink)

Gliomas can display marked changes in the concentrations of energy metabolism molecules such as creatine (Cr), phosphocreatine (PCr) and lactate, as measured using magnetic resonance spectroscopy (MRS). Moreover, the BOLD (blood oxygen level dependent) contrast enhancement in functional magnetic resonance imaging (fMRI) can be reduced or missing within or near gliomas, while neural activity is not significantly reduced (so-called neurovascular decoupling), so that the location of functionally eloquent areas using fMRI can be erroneous. In this paper, we adapt a previously (...) developed model of the coupling between neural activation, energy metabolism and hemodynamics, by including the venous dilatation Balloon model of Buxton and Frank. We show that decreasing the cerebral blood flow (CBF) baseline value, or the CBF increase fraction, results in a decrease of the BOLD signal and an increase of the lactate peak during a sustained activation. Baseline lactate and PCr levels are not significantly affected by CBF baseline reduction, but are altered even by a moderate decrease of mitochondrial respiration. Decreasing the total Cr and PCr concentration reduces the BOLD signal after the initial overshoot. In conclusion, we suggest that the coupled use of BOLD fMRI and MRS could contribute to a better understanding of the neurovascular and metabolic decoupling in gliomas. (shrink)

The existence and properties of the chloroplast genome were established by a combination of genetic methods which identified chloroplast mutations and placed them into a linear sequence or map; and by chemical methods, CsCl density gradient ultracentrifugation and base analysis, which identified non‐nuclear DNA extracted from isolated chloroplasts. These studies, carried out in the 1950s and 1960s, primarily with Chlamydomonas, as well as parallel studies of mitochondrial DNA with yeast and Neurospora, laid the framework for distinguishing organelle and nuclear (...) genomes. On this basis, the coding and regulatory functions of three genomes – nuclear, chloroplast, and mitochondrial – are being addressed in modern plant molecular biology. (shrink)

Transfer RNA (tRNA) modifications play an important role in regulating mRNA translation at the codon level. tRNA modifications can influence codon selection and optimality, thus shifting translation toward specific sets of mRNAs in a dynamic manner. Queuosine (Q) is a tRNA modification occurring at the wobble position. In eukaryotes, queuosine is synthesized by the tRNA‐guanine trans‐glycosylase (TGT) complex, which incorporates the nucleobase queuine (or Qbase) into guanine of the GUN anticodons. Queuine is sourced from gut bacteria and dietary intake. Q (...) was recently shown to be critical for cellular responses to oxidative and mitochondrial stresses, as well as its potential role in neurodegenerative diseases and brain health. These unique features of Q provide an interesting insight into the regulation of mRNA translation by gut bacteria, and the potential health implications. In this review, Q biology is examined in the light of recent literature and nearly 4 decades of research. Q's role in neuropsychiatric diseases and cancer is highlighted and discussed. Given the recent interest in Q, and the new findings, more research is needed to fully comprehend its biological function and disease relevance, especially in neurobiology. (shrink)

The archaeological record is very limited and its analysis has been contentious. Hence, molecular biologists have shifted their attention to molecular dating techniques. Recently on April 2013, the prestigious Cell Press Journal Current Biology published an article (Fu et al. 2013) entitled “A Revised Timescale for Human Evolution Based on Ancient Mitochondrial Genomes”. This paper has twenty authors and they are researchers from the world’s top institutes like Max Planck Institute, Harvard, etc. Respected authors of this paper have (...) emphatically accepted that the fossil record is inadequate and unreliable. These statements clearly substantiate that now biologists are agreeing that fossil records do not provide any significant evidence at all for conventional evolution theory. Despite the well-recorded fact of the continual grand propaganda of Darwinism based on fossil evidence for more than 150 years, in recent times biologists are surprisingly coming up with such statements, based on their confidence that evolution can be explained purely by the genealogical/genomic record provided by modern molecular biology. Still many respected journals (for example the article in Nature, Retallack, 2013) continue to publish articles on fossil evidence to support Darwinian evolution. These incoherently diverse claims prove that Darwinists are struggling with unscientific ideological approaches to explain biodiversity. Darwinian evolutionary theory is not only the basis of modern biology, but also acts as the guiding principle of science and intellectual reasoning for modern civilization. Hence, a scientific understanding of the breakdown of the Darwinian theory of objective evolution is very important for overcoming the traditional scientific temper of mechanistic intellectualism that characterizes this ideology. In my article “21st Century Biology Refutes Darwinian Abiology” (published in two parts in November and December 2012 issues of The Harmonizer: www.mahaprabhu.net/satsanga/harmonizer) it was noted that several recent findings challenge the credibility that random mutations and natural selection can provide a valid basis for justifying the naturalistic evolution of species. The present article summarizes the problems associated with the fossil record and dating techniques, and its implication on the neo-Darwinian mechanistic misconception of biological life as mere molecular chemistry or abiology. An alternative approach based on the Vedāntic view for explaining biodiversity in the light of 21st century biology is also discussed in the end of the article. (shrink)

Apoptosis proteins have a central role in the development and homeostasis of an organism. These proteins are very important for understanding the mechanism of programmed cell death, and their function is related to their types. According to the classification scheme by Zhou and Doctor (2003), the apoptosis proteins are categorized into the following four types: (1) cytoplasmic protein; (2) plasma membrane-bound protein; (3) mitochondrial inner and outer proteins; (4) other proteins. A powerful learning machine, the Support Vector Machine, is (...) applied for predicting the type of a given apoptosis protein by incorporating the sqrt-amino acid composition effect. High success rates were obtained by the re-substitute test (98/98 = 100 %) and the jackknife test (89/98 = 90.8%). (shrink)

Ion channels mediate ion flux across biological membranes and regulate important organellar and cellular tasks. A recent study revealed the presence of four new proteins, the MIM complex (composed by Mim1 and Mim2), Ayr1, OMC7, and OMC8, that are able to form ion‐conducting channels in the outer mitochondria membrane (OMM). These findings strongly indicate that the OMM is endowed with many solute‐specific channels, in addition to porins and known channels mediating protein import into mitochondria. These solute‐specific channels provide essential pathways (...) for the controlled transport of ions and metabolites and may thus add a further layer of specificity to the regulation of mitochondrial function at the organelle‐cytosol and/or inter‐organellar interface. Future studies will be required to fully understand the way(s) of regulation of these new channels and to integrate them into signaling pathways within the cells. (shrink)

In eukaryotes, small amounts of nitrite confer cytoprotection against ischemia/reperfusion‐related tissue damage in vivo, possibly via reduction to nitric oxide (NO) and inhibition of mitochondrial function. Several hemeproteins are involved in this protective mechanism, starting with deoxyhemoglobin, which is capable of reducing nitrite. In facultative aerobic bacteria, such as Pseudomonas aeruginosa, nitrite is reduced to NO by specialized heme‐containing enzymes called cd1 nitrite reductases. The details of their catalytic mechanism are summarized below, together with a hypothesis on the biological (...) role of the unusual d1‐heme, which, in the reduced state, shows unique properties (very high affinity for nitrite and exceptionally fast dissociation of NO). Our results support the idea that the nitrite‐based reactions of contemporary eukaryotes are a vestige of earlier bacterial biochemical pathways. The evidence that nitrite reductase activities of enzymes with different cellular roles and biochemical features still exist today highlights the importance of nitrite in cellular homeostasis. (shrink)

In order to make an attempt at grouping the various aspects of brain functional imaging (fMRI, MRS, EEG-MEG, ...) within a coherent frame, we implemented a model consisting of a system of differential equations, that includes: (1) sodium membrane transport, (2) Na/K ATPase, (3) neuronal energy metabolism (i.e. glycolysis, buffering effect of phosphocreatine, and mitochondrial respiration), (4) blood-brain barrier exchanges and (5) brain hemodynamics, all the processes which are involved in the activation of brain areas. We assumed that the (...) correlation between brain activation and metabolism could be due to either changes in the concentrations of ATP and ADP following activation of Na/K ATPase that result from the changes in ion concentrations, or the involvement, in different phases of metabolism, of a second messenger such as calcium. In this article, we show how this type of model enables interpretation of MRS and fMRI published data that were obtained during prolonged stimulations. (shrink)

With an increasing number of ways to ‘assist’ reproduction, some bioethicists have started to wonder what it takes to become a genetic parent. It is widely agreed that sharing genes is not enough to substantiate the parent–offspring relation, but what is? Without a better understanding of the concept of reproduction, our thinking about parent–offspring relations and the ethical issues surrounding them risk being unprincipled. Here, I address that problem by offering a principled account of reproduction—the Overlap, Development and Persistence account—which (...) I believe best captures the meaning of ‘genetic parenthood’. (shrink)