Ladislav Kováč

Linear mitochondrial genomes: 30 years down the line

At variance with the earlier belief that mitochondrial genomes are represented by circular DNA molecules, a large number of organisms have been found to carry linear mitochondrial DNA. Studies of linear mitochondrial genomes might provide a novel view on the evolutionary history of organelle genomes and contribute to delineating mechanisms of maintenance and functioning of telomeres. Because linear mitochondrial DNA is present in a number of human pathogens, its replication mechanisms might become a target for drugs that would not interfere with replication of human circular mitochondrial DNA.

Linear mitochondrial DNAs from yeasts: telomeres with large tandem repetitions

The terminal structure of the linear mitochondrial DNA (mtDNA) from the yeast Candida parapsilosis was investigated. This mtDNA, 30 kb long, has symmetrical ends forming inverted terminal repeats. These repeats are made up of a variable number of tandemly repeating units of 738 by each; the terminal nucleotide corresponds to a precise position within the last repeat unit sequence. The ends had an open structure accessible to enzymes, with a 5′ single-stranded extension of about 110 nucleotides. No circular forms were detected in the DNA preparations. Two other unrelated species, Pichia philodendra and Candida salmanticensis also appear to have a linear mtDNA of similar organization. These linear DNAs (which we name Type 2 linear mtDNAs) are distinct from the previously described linear mtDNAs of yeasts whose termini are formed by a closed hairpin loop (Type 1 linear mtDNA). The terminal structure of C. parapsilosis mtDNA is reminiscent of the linear mitochondrial genomes of the ciliate Tetrahymena although, in the latter, the telomeric tandem repeat unit is considerably shorter.

Information and knowledge in biology: time for reappraisal.

The second law of thermodynamics accounts for irreversibility of processes in the universe. As a statement about increasing disorder, it also plays a central role in creating order. Structuring is a way of how to increase the rate of dissipation of matter and energy. This is the reason why chemical reactions on Earth have produced a profusion of structures. Chemical structures with particularly high stability, maintained by continual dissipation, are designated, somewhat arbitrarily, as living systems. To preserve stability, organisms are unceasingly performing ontic work, assisted by epistemic work. Biological evolution is a progressing process of knowledge acquisition (cognition) and, correspondingly, of growth of complexity. The acquired knowledge represents epistemic complexity. Biological species are the main “bookkeepers” of acquired knowledge, with individual members of the species functioning as “explorers” of novelty. Science, a human species-specific mode of acquiring knowledge, abounds in metaphors no less than art. In the postgenomic era, the metaphor of information, along with the related metaphor of selfish genes, may need reconsideration and/or complementation. The world of great complexity, which is becoming the focus of studies of contemporary biology, may require – similarly as it is the case of quantum physics – descriptions based on the principle of complementarity. Embodied knowledge, molecular engine, ontic and epistemic work, and triggering may become parts of a new conceptual armory.

Life, chemistry and cognition

As Shakespeare wrote in Much Ado About Nothing , “…there was never yet philosopher, That could endure the toothache patiently…” Indeed, perhaps the fundamental existential human experience is suffering. Under unbearable pain or distress, even the staunchest advocates of solipsism will eventually rescind their conviction that the world is only an illusion. What makes suffering so powerful in convincing us that we and the world are real is the fact that we experience it; we do not merely observe it. “I experience, therefore I am” would thus describe the indisputable human condition more appropriately than the classical statement “I think, therefore I am.”nnThe latter statement was the foundation on which the seventeenth century French philosopher Rene Descartes built his conception of the world. For Descartes (also known as Cartesius), thinking was the exclusive capacity of the incorporeal mind, the soul, which he defined as a thinking substance. Moreover, he claimed that only humans have a soul, and only they can reason; all other organisms, including monkeys as he explicitly posited, were mere automatons built of flesh and bones. Descartes did not deny life to animals or equate them with human made machines, as has often been imputed to him. In contrast to inanimate machines, animals had corporeal spirits, which humans had too, and exhibited sensations and passions. Yet in Descartes view, the behaviour of non human animals could easily be explained solely by the function and constitution of their organs; in contrast to humans, they did not have any capacity for pure thought free from natural impulses and passions. In his argument, he referred to the ancient Greek philosopher Epiktetos, who stated that you are not your body—your body is just finely moulded clay. To explain how the soul caused human reasoning, Descartes proposed an intriguing mechanism: the human …

Bioenergetics: A key to brain and mind.

Natural life is chemical. Chemistry, not abstract logic, determines and constrains its potentialities. One of the potentialities is cognition. Humans have two equivalent cognitive systems: the immune and the nervous ones. The principle of functioning is the same for both: rooted in the previously acquired and embodied knowledge, the system is intrinsically generating many new chemical states and the environment selects and stabilizes appropriate of them. From the fundamental level of complicated brain chemistry (biochemese) higher levels emerge: the physiological (physiologese) and the mental (mentalese). Processes are causal at the basic chemical level; they are mere isomorphic, tautological translations at the other levels. The thermodynamic necessity to maintain correlations in the complicated chemical system and to generate variants make the nervous system energetically expensive: it runs continuously at full speed and external inputs only trigger and modulate the ongoing dynamics. Models of the brain as a universal computer are utterly inadequate.

An overlooked riddle of life's origins: energy-dependent nucleic acid unzipping.

The imposing progress in understanding contemporary life forms on Earth and in manipulating them has not been matched by a comparable progress in understanding the origins of life. This paper argues that a crucial problem of unzipping of the double helix molecule of nucleic acid during its replication has been underrated, if not plainly overlooked, in the theories of life’s origin and evolution. A model is presented of how evolution may have solved the problem in its early phase. Similar to several previous models, the model envisages the existence of a protocell, in which osmotic disbalance is being created by accumulation of synthetic products resulting in expansion and division of the protocell. Novel in the model is the presence in the protocell of a double-stranded nucleic acid, with each of its two strands being affixed by its 3′-terminus to the opposite sides of the membrane of a protocell. In the course of the protocell expansion, osmotic force is utilized to pull the two strands longitudinally in opposite directions, unzipping the helix and partitioning the strands between the two daughter protocells. The model is also being used as a background for arguments of why life need operate in cycles. Many formal models of life’s origin and evolution have not taken into account the fact that logical possibility does not equal thermodynamic feasibility. A system of self-replication has to consist of both replicators and replicants.

Two Cultures Revisited: New Widening Gaps

Aristotle continues to be a highly cited author in cultural sciences (human and social sciences) and humanities. In the last two decades, his work attracted up to a hundred times more attention than the work of Konrad Lorenz or Edward O. Wilson, who have attempted to synthesize new knowledge on behavior and society and proposed alternatives to traditional, intuitively appealing, explanations. Aristotles interpretations of the world, which appear to be intuitive to the human mind, were abandoned in natural sciences upon introduction of the experimental method. Human intuition may have been appropriate in conditions under which it was originally selected: for life of small non-anonymous groups of hunters and gatherers in the savannah. Intuition confines human understanding to a simple reality circumscribed by a boundary that can be called Aristotles barrier. The barrier may only be crossed by experimentation, which is largely missing in cultural sciences. Snows concept of two cultures may be revisited to characterize a splitting of natural sciences versus cultural sciences. It may also be applied to a widening gulf between science and technoscience. Diverging of the two cultures may have far-reaching consequences for prospects of humankinds survival.

'Finitics'. A plea for biological realism.

The history of human thought can be separated into two periods: before Darwin (BD) and after Darwin (AD). The former period covers 150,000 years of the existence of modern humans; the latter a thousand times less. Yet, as this paper argues, the burden of pre‐Darwinian thinking continues to prevent us from realistically appreciating the present evolutionary stage of the human species. Therefore, I suggest that it might be time to substitute our current illusions, either about a bright future or imminent doomsday for humanity, with a radical Darwinian alternative.nnBefore Charles Darwin (1809–1882) published his theory of evolution in The Origin of Species in 1859, humans explained the existence, order and purpose of all things in nature by either natural or supernatural design. The fundamental tenet of Darwins theory and the foundation of AD thought is the universality of Darwinian dynamics: complexity is steadily increasing and new knowledge is accumulating in the universe by uncorrelated variations and selection from the variants. However, selection—or, in the more precise words of the evolutionary biologist Ernst Mayr (1904–2005), non‐random elimination—needs time to be effective.nnA second Darwinian insight is the assertion—which Darwin adopted from British economist Thomas Malthus (1766–1834)—that life is subject to the law of exponential growth: the rate of change of a variable Q is a linear function of its present quantity: d Q /d t = kQ ; Q = cekt (Fig 1A). The population of any species would literally explode if its dynamics were not ‘moderated’ by the incessant ‘struggle for existence’ of each individual organism. Our ancestors were unlikely to encounter any exponential processes in their individual lifetimes, and so the human mind has been shaped to be successful by making linear extrapolations. Even a biologist who inoculates a culture with Escherichia coli and harvests a few …

Science, an essential part of culture Ignoring the fact that science is an integral part of human culture is a serious error if we want to overcome humanity's problems

Ignoring the fact that science is an integral part of human culture is a serious error if we want to overcome humanitys problems

The 20 W sleep-walkers.

The energy output of the resting adult human body is equal to the power of a 100 W electrical light bulb. With a hard physical load, it could be up to seven times larger. All humans on Earth warm up the universe by 650 GJ of thermal energy every second by their mere existence—although, by virtue of technology, humankinds total energy output is actually 25 times larger. Each living cell contains millions of molecular machines. Other than macroscopic machines, these tiny machines constantly jiggle owing to the Brownian motion, so they frequently break down and must be continually repaired and restored. The basal energy demand is used for maintenance, repair and renewal.nnRemarkably, the brain alone consumes 20% of the bodys chemical energy, even though it accounts for only 2% of the bodys mass. Metaphorically speaking, we all have a 20 W light bulb burning in our head, even when we lie still in complete darkness doing physically …