Moderate sex between protocells can balance between a decrease in assortment load and an increase in parasite spread.

Sexual reproduction is widespread in nature despite the different kinds of cost that it entails. We do not know exactly when the first sexual process took place and especially why it was beneficial at first. It is clearer why sex is advantageous for the prokaryotes and eukaryotes but the benefit of sex for protocells with individually replicating ribozymes is not yet fully understood. In this context sex is the simple horizontal gene transfer among two protocells that undergo transient fusion. Many authors argue that horizontal gene transfer (HGT) was very common in the early stage of evolution. However, HGT is a risky mechanism considering both the disruption of optimal compositions and the spread of parasites among protocells. In order to test the effects of HGT on the fitness of a protocell population, we explored by numerical simulations those conditions under which fusion might have been beneficial. We investigated multiple conceivable types of fusion in the stochastic corrector model framework and we considered the spread of parasites in every case. Protocells contain up to five species of unlinked, essential ribozymes; if a protocell has the same amount of each, it reaches maximum fitness. Fusion is dangerous not only due to the spread of parasites but also because it can ruin the cells with balanced ribozyme composition. We show that fusion can restore the ribozyme composition of the protocells under certain circumstances (high gene count, intermediate split size and low rate of fusion) and thus it can decrease the effect of the genetic load. Fusion could have been a useful early mechanism in contributing to the reliable coexistence of the different ribozymes before the spread of the chromosomes.

How Fast Does Darwin's Elephant Population Grow?

In "The Origin of Species," Darwin describes a hypothetical example illustrating that large, slowly reproducing mammals such as the elephant can reach very large numbers if population growth is not affected by regulating factors. The elephant example has since been cited in various forms in a wide variety of books, ranging from educational material to encyclopedias. However, Darwin's text was changed over the six editions of the book, although some errors in the mathematics persisted throughout. In addition, full details of the problem remained hidden in his correspondence with readers of the Origin. As a result, Darwin's example is very often misinterpreted, misunderstood or presented as if it were a fact. We show that the population growth of Darwin's elephant population can be modeled by the Leslie matrix method, which we generalize here to males as well. Darwin's most often cited figure, about 19 million elephants after 750 years is not a typical outcome, actually a very unlikely result under more realistic, although still hypothetical situations. We provide a recursion formula suggesting that Darwin's original model corresponds to a tribonacci series, a proof showing that sex ratio is constant over all age classes, and a derivation of a generating function of the sequence.

Maximal gene number maintainable by stochastic correction - The second error threshold.

There is still no general solution to Eigen׳s Paradox, the chicken-or-egg problem of the origin of life: neither accurate copying, nor long genomes could have evolved without one another being established beforehand. But an array of small, individually replicating genes might offer a workaround, provided that multilevel selection assists the survival of the ensemble. There are two key difficulties that such a system has to overcome: the non-synchronous replication of genes, and their random assortment into daughter cells (the units of higher-level selection) upon fission. Here we find, using the Stochastic Corrector Model framework, that a large number (τ≥90) of genes can coexist. Furthermore, the system can tolerate about 10% replication rate asymmetry (competition) among the genes. On this basis, we put forward a plausible (and testable!) scenario for how novel genes could have been incorporated into early living systems: a route to complex metabolism.

Evolution of the division of labor between genes and enzymes in the RNA world.

The RNA world is a very likely interim stage of the evolution after the first replicators and before the advent of the genetic code and translated proteins. Ribozymes are known to be able to catalyze many reaction types, including cofactor-aided metabolic transformations. In a metabolically complex RNA world, early division of labor between genes and enzymes could have evolved, where the ribozymes would have been transcribed from the genes more often than the other way round, benefiting the encapsulating cells through this dosage effect. Here we show, by computer simulations of protocells harboring unlinked RNA replicators, that the origin of replicational asymmetry producing more ribozymes from a gene template than gene strands from a ribozyme template is feasible and robust. Enzymatic activities of the two modeled ribozymes are in trade-off with their replication rates, and the relative replication rates compared to those of complementary strands are evolvable traits of the ribozymes. The degree of trade-off is shown to have the strongest effect in favor of the division of labor. Although some asymmetry between gene and enzymatic strands could have evolved even in earlier, surface-bound systems, the shown mechanism in protocells seems inevitable and under strong positive selection. This could have preadapted the genetic system for transcription after the subsequent origin of chromosomes and DNA.

Real ribozymes suggest a relaxed error threshold.

The error threshold for replication, the critical copying fidelity below which the fittest genotype deterministically disappears, limits the length of the genome that can be maintained by selection. Primordial replication must have been error-prone, and so early replicators are thought to have been necessarily short. The error threshold also depends on the fitness landscape. In an RNA world, many neutral and compensatory mutations can raise the threshold, below which the functional phenotype, rather than a particular sequence, is still present. Here we show, on the basis of comparative analysis of two extensively mutagenized ribozymes, that with a copying fidelity of 0.999 per digit per replication the phenotypic error threshold rises well above 7,000 nucleotides, which permits the selective maintenance of a functionally rich riboorganism with a genome of more than 100 different genes, the size of a tRNA. This requires an order of magnitude of improvement in the accuracy of in vitro-generated polymerase ribozymes. Incidentally, this genome size coincides with that estimated for a minimal cell achieved by top-down analysis, omitting the genes dealing with translation.

Strategy diversity stabilizes mutualism through investment cycles, phase polymorphism, and spatial bubbles.

There is continuing interest in understanding factors that facilitate the evolution and stability of cooperation within and between species. Such interactions will often involve plasticity in investment behavior, in response to the interacting partner's investments. Our aim here is to investigate the evolution and stability of reciprocal investment behavior in interspecific interactions, a key phenomenon strongly supported by experimental observations. In particular, we present a comprehensive analysis of a continuous reciprocal investment game between mutualists, both in well-mixed and spatially structured populations, and we demonstrate a series of novel mechanisms for maintaining interspecific mutualism. We demonstrate that mutualistic partners invariably follow investment cycles, during which mutualism first increases, before both partners eventually reduce their investments to zero, so that these cycles always conclude with full defection. We show that the key mechanism for stabilizing mutualism is phase polymorphism along the investment cycle. Although mutualistic partners perpetually change their strategies, the community-level distribution of investment levels becomes stationary. In spatially structured populations, the maintenance of polymorphism is further facilitated by dynamic mosaic structures, in which mutualistic partners form expanding and collapsing spatial bubbles or clusters. Additionally, we reveal strategy-diversity thresholds, both for well-mixed and spatially structured mutualistic communities, and discuss factors for meeting these thresholds, and thus maintaining mutualism. Our results demonstrate that interspecific mutualism, when considered as plastic investment behavior, can be unstable, and, in agreement with empirical observations, may involve a polymorphism of investment levels, varying both in space and in time. Identifying the mechanisms maintaining such polymorphism, and hence mutualism in natural communities, provides a significant step towards understanding the coevolution and population dynamics of mutualistic interactions.

(How) should researchers publicize their research papers before peer review?

News outlets publicize scientific research findings that have not been peer reviewed yet, and they often do it with active contribution by the authors of the unpublished manuscripts. While researchers are aware of the importance of the peer review process and what it means to discuss findings before manuscripts are accepted for publication, the general public is not. It is imperative to ensure that researchers provide reliable scientific knowledge to each other and to the public, as well as to preserve reliance on the scientific process and peer review. For these reasons, researchers should be more cautious in communicating unpublished work to the public and more accurate about the status of the presented scientific information.

Do pathogens always evolve to be less virulent? The virulence-transmission trade-off in light of the COVID-19 pandemic.

The direction the evolution of virulence takes in connection with any pathogen is a long-standing question. Formerly, it was theorized that pathogens should always evolve to be less virulent. As observations were not in line with this theoretical outcome, new theories emerged, chief among them the transmission-virulence trade-off hypotheses, which predicts an intermediate level of virulence as the endpoint of evolution. At the moment, we are very much interested in the future evolution of COVID-19's virulence. Here, we show that the disease does not fulfill all the assumptions of the hypothesis. In the case of COVID-19, a higher viral load does not mean a higher risk of death; immunity is not long-lasting; other hosts can act as reservoirs for the virus; and death as a consequence of viral infection does not shorten the infectious period. Consequently, we cannot predict the short- or long-term evolution of the virulence of COVID-19.

Is there still evolution in the human population?

It is often claimed that humanity has stopped evolving because modern medicine erased all selection on survival. Even if that would be true, and it is not, there would be other mechanisms of evolution which could still led to changes in allelic frequencies. Here I show, by applying basic evolutionary genetics knowledge, that we expect humanity to evolve. The results from genome sequencing projects have repeatedly affirmed that there are still recent signs of selection in our genomes. I give some examples of such adaptation. Then I briefly discuss what our evolutionary future has in store for us.

State-controlled epidemic in a game against a novel pathogen.

The pandemic reminded us that the pathogen evolution still has a serious effect on human societies. States, however, can prepare themselves for the emergence of a novel pathogen with unknown characteristics by analysing potential scenarios. Game theory offers such an appropriate tool. In our game-theoretical framework, the state is playing against a pathogen by introducing non-pharmaceutical interventions to fulfil its socio-political goals, such as guaranteeing hospital care to all needed patients, keeping the country functioning, while the applied social restrictions should be as soft as possible. With the inclusion of activity and economic sector dependent transmission rate, optimal control of lockdowns and health care capacity management is calculated. We identify the presence and length of a pre-symptomatic infectious stage of the disease to have the greatest effect on the probability to cause a pandemic. Here we show that contrary to intuition, the state should not strive for the great expansion of its health care capacities even if its goal is to provide care for all requiring it and minimize the cost of lockdowns.

The major evolutionary transitions and codes of life.

Major evolutionary transitions as well as the evolution of codes of life are key elements in macroevolution which are characterized by increase in complexity Major evolutionary transitions ensues by a transition in individuality and by the evolution of a novel mode of using, transmitting or storing information. Here is where codes of life enter the picture: they are arbitrary mappings between different (mostly) molecular species. This flexibility allows information to be employed in a variety of ways, which can fuel evolutionary innovation. The collation of the list of major evolutionary transitions and the list of codes of life show a clear pattern: codes evolved prior to a major evolutionary transition and then played roles in the transition and/or in the transformation of the new individual. The evolution of a new code of life is in itself not a major evolutionary transition but allow major evolutionary transitions to happen. This could help us to identify new organic codes.

The Mutational Robustness of the Genetic Code and Codon Usage in Environmental Context: A Non-Extremophilic Preference?

The genetic code was evolved, to some extent, to minimize the effects of mutations. The effects of mutations depend on the amino acid repertoire, the structure of the genetic code and frequencies of amino acids in proteomes. The amino acid compositions of proteins and corresponding codon usages are still under selection, which allows us to ask what kind of environment the standard genetic code is adapted to. Using simple computational models and comprehensive datasets comprising genomic and environmental data from all three domains of Life, we estimate the expected severity of non-synonymous genomic mutations in proteins, measured by the change in amino acid physicochemical properties. We show that the fidelity in these physicochemical properties is expected to deteriorate with extremophilic codon usages, especially in thermophiles. These findings suggest that the genetic code performs better under non-extremophilic conditions, which not only explains the low substitution rates encountered in halophiles and thermophiles but the revealed relationship between the genetic code and habitat allows us to ponder on earlier phases in the history of Life.

Phylogenetic analysis of mutational robustness based on codon usage supports that the standard genetic code does not prefer extreme environments.

The mutational robustness of the genetic code is rarely discussed in the context of biological diversity, such as codon usage and related factors, often considered as independent of the actual organism's proteome. Here we put the living beings back to picture and use distortion as a metric of mutational robustness. Distortion estimates the expected severities of non-synonymous mutations measuring it by amino acid physicochemical properties and weighting for codon usage. Using the biological variance of codon frequencies, we interpret the mutational robustness of the standard genetic code with regards to their corresponding environments and genomic compositions (GC-content). Employing phylogenetic analyses, we show that coding fidelity in physicochemical properties can deteriorate with codon usages adapted to extreme environments and these putative effects are not the artefacts of phylogenetic bias. High temperature environments select for codon usages with decreased mutational robustness of hydrophobic, volumetric, and isoelectric properties. Selection at high saline concentrations also leads to reduced fidelity in polar and isoelectric patterns. These show that the genetic code performs best with mesophilic codon usages, strengthening the view that LUCA or its ancestors preferred lower temperature environments. Taxonomic implications, such as rooting the tree of life, are also discussed.

Cooperators Unite! Assortative linking promotes cooperation particularly for medium sized associations.

BACKGROUND: Evolution of cooperative behaviour is widely studied in different models where interaction is heterogeneous, although static among individuals. However, in nature individuals can often recognize each other and chose, besides to cooperate or not, to preferentially associate with or to avoid certain individuals.Here we consider a dynamical interaction graph, in contrast to a static one. We propose several rules of rejecting unwanted partners and seeking out new ones, and study the probability of emergence and maintenance of cooperation on these dynamic networks. RESULTS: Our simulations reveal that cooperation can evolve and be stable in the population if we introduce preferential linking, even if defectors can perform it too. The fixation of cooperation has higher probability than that of on static graphs, and this effect is more prevalent at high benefit to cost ratios. We also find an optimal number of partners, for which the fixation probability of cooperation shows a maximum. CONCLUSIONS: The ability to recognize, seek out or avoid interaction partners based on the outcome of past interactions has an important effect on the emergence of cooperation. Observations about the number of partners in natural cooperating groups are in concordance with the result of our model.

From self-replication to replicator systems en route to de novo life.

The process by which chemistry can give rise to biology remains one of the biggest mysteries in contemporary science. The de novo synthesis and origin of life both require the functional integration of three key characteristics - replication, metabolism and compartmentalization - into a system that is maintained out of equilibrium and is capable of open-ended Darwinian evolution. This Review takes systems of self-replicating molecules as starting points and describes the steps necessary to integrate additional characteristics of life. We analyse how far experimental self-replicators have come in terms of Darwinian evolution. We also cover models of replicator communities that attempt to solve Eigen's paradox, whereby accurate replication needs complex machinery yet obtaining such complex self-replicators through evolution requires accurate replication. Successful models rely on a collective metabolism and a way of (transient) compartmentalization, suggesting that the invention and integration of these two characteristics is driven by evolution. Despite our growing knowledge, there remain numerous key challenges that may be addressed by a combined theoretical and experimental approach.

In silico detection of tRNA sequence features characteristic to aminoacyl-tRNA synthetase class membership.

Aminoacyl tRNA synthetases (aaRS) are grouped into Class I and II based on primary and tertiary structure and enzyme properties suggesting two independent phylogenetic lineages. Analogously, tRNA molecules can also form two respective classes, based on the class membership of their corresponding aaRS. Although some aaRS-tRNA interactions are not extremely specific and require editing mechanisms to avoid misaminoacylation, most aaRS-tRNA interactions are rather stereospecific. Thus, class-specific aaRS features could be mirrored by class-specific tRNA features. However, previous investigations failed to detect conserved class-specific nucleotides. Here we introduce a discrete mathematical approach that evaluates not only class-specific 'strictly present', but also 'strictly absent' nucleotides. The disjoint subsets of these elements compose a unique partition, named extended consensus partition (ECP). By analyzing the ECP for both Class I and II tDNA sets from 50 (13 archaeal, 30 bacterial and 7 eukaryotic) species, we could demonstrate that class-specific tRNA sequence features do exist, although not in terms of strictly conserved nucleotides as it had previously been anticipated. This finding demonstrates that important information was hidden in tRNA sequences inaccessible for traditional statistical methods. The ECP analysis might contribute to the understanding of tRNA evolution and could enrich the sequence analysis tool repertoire.

Five main phases of landscape degradation revealed by a dynamic mesoscale model analysing the splitting, shrinking, and disappearing of habitat patches.

The ecological consequences of habitat loss and fragmentation have been intensively studied on a broad, landscape-wide scale, but have less been investigated on the finer scale of individual habitat patches, especially when considering dynamic turnovers in the habitability of sites. We study changes to individual patches from the perspective of the inhabitant organisms requiring a minimum area for survival. With patches given by contiguous assemblages of discrete habitat sites, the removal of a single site necessarily causes one of the following three elementary local events in the affected patch: splitting into two or more pieces, shrinkage without splitting, or complete disappearance. We investigate the probabilities of these events and the effective size of the habitat removed by them from the population's living area as the habitat landscape gradually transitions from pristine to totally destroyed. On this basis, we report the following findings. First, we distinguish four transitions delimiting five main phases of landscape degradation: (1) when there is only a little habitat loss, the most frequent event is the shrinkage of the spanning patch; (2) with more habitat loss, splitting becomes significant; (3) splitting peaks; (4) the remaining patches shrink; and (5) finally, they gradually disappear. Second, organisms that require large patches are especially sensitive to phase 3. This phase emerges at a value of habitat loss that is well above the percolation threshold. Third, the effective habitat loss caused by the removal of a single habitat site can be several times higher than the actual habitat loss. For organisms requiring only small patches, this amplification of losses is highest during phase 4 of the landscape degradation, whereas for organisms requiring large patches, it peaks during phase 3.

The evolution of the genetic code: Impasses and challenges.

The origin of the genetic code and translation is a "notoriously difficult problem". In this survey we present a list of questions that a full theory of the genetic code needs to answer. We assess the leading hypotheses according to these criteria. The stereochemical, the coding coenzyme handle, the coevolution, the four-column theory, the error minimization and the frozen accident hypotheses are discussed. The integration of these hypotheses can account for the origin of the genetic code. But experiments are badly needed. Thus we suggest a host of experiments that could (in)validate some of the models. We focus especially on the coding coenzyme handle hypothesis (CCH). The CCH suggests that amino acids attached to RNA handles enhanced catalytic activities of ribozymes. Alternatively, amino acids without handles or with a handle consisting of a single adenine, like in contemporary coenzymes could have been employed. All three scenarios can be tested in in vitro compartmentalized systems.

Ecology and Evolution in the RNA World Dynamics and Stability of Prebiotic Replicator Systems.

As of today, the most credible scientific paradigm pertaining to the origin of life on Earth is undoubtedly the RNA World scenario. It is built on the assumption that catalytically active replicators (most probably RNA-like macromolecules) may have been responsible for booting up life almost four billion years ago. The many different incarnations of nucleotide sequence (string) replicator models proposed recently are all attempts to explain on this basis how the genetic information transfer and the functional diversity of prebiotic replicator systems may have emerged, persisted and evolved into the first living cell. We have postulated three necessary conditions for an RNA World model system to be a dynamically feasible representation of prebiotic chemical evolution: (1) it must maintain and transfer a sufficient diversity of information reliably and indefinitely, (2) it must be ecologically stable and (3) it must be evolutionarily stable. In this review, we discuss the best-known prebiotic scenarios and the corresponding models of string-replicator dynamics and assess them against these criteria. We suggest that the most popular of prebiotic replicator systems, the hypercycle, is probably the worst performer in almost all of these respects, whereas a few other model concepts (parabolic replicator, open chaotic flows, stochastic corrector, metabolically coupled replicator system) are promising candidates for development into coherent models that may become experimentally accessible in the future.

Transient compartmentalization of RNA replicators prevents extinction due to parasites.

The appearance of molecular replicators (molecules that can be copied) was probably a critical step in the origin of life. However, parasitic replicators would take over and would have prevented life from taking off unless the replicators were compartmentalized in reproducing protocells. Paradoxically, control of protocell reproduction would seem to require evolved replicators. We show here that a simpler population structure, based on cycles of transient compartmentalization (TC) and mixing of RNA replicators, is sufficient to prevent takeover by parasitic mutants. TC tends to select for ensembles of replicators that replicate at a similar rate, including a diversity of parasites that could serve as a source of opportunistic functionality. Thus, TC in natural, abiological compartments could have allowed life to take hold.