Forward-in-time simulation of chromosomal rearrangements: The invisible backbone that sustains long-term adaptation.

While chromosomal rearrangements are ubiquitous in all domains of life, very little is known about their evolutionary significance, mostly because, apart from a few specifically studied and well-documented mechanisms (interaction with recombination, gene duplication, etc.), very few models take them into account. As a consequence, we lack a general theory to account for their direct and indirect contributions to evolution. Here, we propose Aevol, a forward-in-time simulation platform specifically dedicated to unravelling the evolutionary significance of chromosomal rearrangements (CR) compared to local mutations (LM). Using the platform, we evolve populations of organisms in four conditions characterized by an increasing diversity of mutational operators-from substitutions alone to a mix of substitutions, InDels and CR-but with a constant global mutational rate. Despite being almost invisible in the phylogeny owing to the scarcity of their fixation in the lineages, we show that CR make a decisive contribution to the evolutionary dynamics by comparing the outcome in these four conditions. As expected, chromosomal rearrangements allow fast expansion of the gene repertoire through gene duplication, but they also reduce the effect of diminishing-returns epistasis, hence sustaining adaptation on the long-run. At last, we show that chromosomal rearrangements tightly regulate the size of the genome through indirect selection for reproductive robustness. Overall, these results confirm the need to improve our theoretical understanding of the contribution of chromosomal rearrangements to evolution and show that dedicated platforms like Aevol can efficiently contribute to this agenda.

Seaview Version 5: A Multiplatform Software for Multiple Sequence Alignment, Molecular Phylogenetic Analyses, and Tree Reconciliation.

We present Seaview version 5, a multiplatform program to perform multiple alignment and phylogenetic tree building from molecular sequence data. Seaview provides network access to sequence databases, alignment with arbitrary algorithm, parsimony, distance and maximum likelihood tree building with PhyML, and display, printing, and copy-to-clipboard or to SVG files of rooted or unrooted, binary or multifurcating phylogenetic trees. While Seaview is primarily a program providing a graphical user interface to guide the user into performing desired analyses, Seaview possesses also a command-line mode adequate for user-provided scripts. Seaview version 5 introduces the ability to reconcile a gene tree with a reference species tree and use this reconciliation to root and rearrange the gene tree. Seaview is freely available at http://doua.prabi.fr/software/seaview .

Treerecs: an integrated phylogenetic tool, from sequences to reconciliations.

MOTIVATION: Gene and species tree reconciliation methods are used to interpret gene trees, root them and correct uncertainties that are due to scarcity of signal in multiple sequence alignments. So far, reconciliation tools have not been integrated in standard phylogenetic software and they either lack performance on certain functions, or usability for biologists. RESULTS: We present Treerecs, a phylogenetic software based on duplication-loss reconciliation. Treerecs is simple to install and to use. It is fast and versatile, has a graphic output, and can be used along with methods for phylogenetic inference on multiple alignments like PLL and Seaview. AVAILABILITY AND IMPLEMENTATION: Treerecs is open-source. Its source code (C++, AGPLv3) and manuals are available from https://project.inria.fr/treerecs/.

The Complexity Ratchet: Stronger than Selection, Stronger than Evolvability, Weaker than Robustness.

Using the in silico experimental evolution platform Aevol, we have tested the existence of a complexity ratchet by evolving populations of digital organisms under environmental conditions in which simple organisms can very well thrive and reproduce. We observed that in most simulations, organisms become complex although such organisms are a lot less fit than simple ones and have no robustness or evolvability advantage. This excludes selection from the set of possible explanations for the evolution of complexity. However, complementary experiments showed that selection is nevertheless necessary for complexity to evolve, also excluding non-selective effects. Analyzing the long-term fate of complex organisms, we showed that complex organisms almost never switch back to simplicity despite the potential fitness benefit. On the contrary, they consistently accumulate complexity in the long term, meanwhile slowly increasing their fitness but never overtaking that of simple organisms. This suggests the existence of a complexity ratchet powered by negative epistasis: Mutations leading to simple solutions, which are favorable at the beginning of the simulation, become deleterious after other mutations-leading to complex solutions-have been fixed. This also suggests that this complexity ratchet cannot be beaten by selection, but that it can be overthrown by robustness because of the constraints it imposes on the coding capacity of the genome.

In silico experimental evolution: a tool to test evolutionary scenarios.

Comparative genomics has revealed that some species have exceptional genomes, compared to their closest relatives. For instance, some species have undergone a strong reduction of their genome with a drastic reduction of their genic repertoire. Deciphering the causes of these atypical trajectories can be very difficult because of the many phenomena that are intertwined during their evolution (e.g. changes of population size, environment structure and dynamics, selection strength, mutation rates...). Here we propose a methodology based on synthetic experiments to test the individual effect of these phenomena on a population of simulated organisms. We developed an evolutionary model--aevol--in which evolutionary conditions can be changed one at a time to test their effects on genome size and organization (e.g. coding ratio). To illustrate the proposed approach, we used aevol to test the effects of a strong reduction in the selection strength on a population of (simulated) bacteria. Our results show that this reduction of selection strength leads to a genome reduction of ~35% with a slight loss of coding sequences (~15% of the genes are lost--mainly those for which the contribution to fitness is the lowest). More surprisingly, under a low selection strength, genomes undergo a strong reduction of the noncoding compartment (~55% of the noncoding sequences being lost). These results are consistent with what is observed in reduced Prochlorococcus strains (marine cyanobacteria) when compared to close relatives.

Preoperative evaluation and risk management.

All colorectal operations carry significant associated risk. To facilitate the best outcomes it is essential to perform a comprehensive evaluation of patient risk preoperatively. Once risk factors are identified the appropriate steps must be taken to minimize their effects. The evaluation of the patient can be broken down by organ systems such as cardiac, pulmonary, hepatic, renal, and gastrointestinal. Additionally, one can assess whether the patient is at risk for infection, hyperglycemia, malnutrition, venous thromboembolism, and anemia. There are many preemptive steps that can be taken to improve patient outcomes in all of these categories.