An experimental study of adaptive control for evolutionary algorithms

International audience

I. Quantal effects in biochemical cooperativity and a proposed mechanism for the differentiation of calcium signaling in synaptic plasticity. II. Evolutionary algorithms for the optimization of methods in computational chemistry

In Part 1 of this thesis, we propose that biochemical cooperativity is a fundamentally non-ideal process. We show quantal effects underlying biochemical cooperativity and highlight apparent ergodic breaking at small volumes. The apparent ergodic breaking manifests itself in a divergence of deterministic and stochastic models. We further predict that this divergence of deterministic and stochastic results is a failure of the deterministic methods rather than an issue of stochastic simulations.

Ergodic breaking at small volumes may allow these molecular complexes to function as switches to a greater degree than has previously been shown. We propose that this ergodic breaking is a phenomenon that the synapse might exploit to differentiate Ca$^{2+}$ signaling that would lead to either the strengthening or weakening of a synapse. Techniques such as lattice-based statistics and rule-based modeling are tools that allow us to directly confront this non-ideality. A natural next step to understanding the chemical physics that underlies these processes is to consider \textit{in silico} specifically atomistic simulation methods that might augment our modeling efforts.

In the second part of this thesis, we use evolutionary algorithms to optimize \textit{in silico} methods that might be used to describe biochemical processes at the subcellular and molecular levels. While we have applied evolutionary algorithms to several methods, this thesis will focus on the optimization of charge equilibration methods. Accurate charges are essential to understanding the electrostatic interactions that are involved in ligand binding, as frequently discussed in the first part of this thesis.

An evolutionary squeaky wheel optimisation approach to personnel scheduling

The quest for robust heuristics that are able to solve more than one problem is ongoing. In this paper, we present, discuss and analyse a technique called Evolutionary Squeaky Wheel Optimisation and apply it to two different personnel scheduling problems. Evolutionary Squeaky Wheel Optimisation improves the original Squeaky Wheel Optimisation’s effectiveness and execution speed by incorporating two additional steps (Selection and Mutation) for added evolution. In the Evolutionary Squeaky Wheel Optimisation, a cycle of Analysis-Selection-Mutation-Prioritization-Construction continues until stopping conditions are reached. The aim of the Analysis step is to identify below average solution components by calculating a fitness value for all components. The Selection step then chooses amongst these underperformers and discards some probabilistically based on fitness. The Mutation step further discards a few components at random. Solutions can become incomplete and thus repairs may be required. The repair is carried out by using the Prioritization step to first produce priorities that determine an order by which the following Construction step then schedules the remaining components. Therefore, improvements in the Evolutionary Squeaky Wheel Optimisation is achieved by selective solution disruption mixed with iterative improvement and constructive repair. Strong experimental results are reported on two different domains of personnel scheduling: bus and rail driver scheduling and hospital nurse scheduling.

The Myosin Heavy Chain specific A4.1025 antibody discriminates different cardiac segments in ancient groups of gnathostomes: Morphological and evolutionary implications

The pan-Myosin Heavy Chain (pan-MyHC) marker MF20 have been reported to show similar, homogeneous signal in the myocardial segments of the heart of teleosts and tetrapods. However, in an ongoing study of the myocardial structure of the dogfish (Scyliorhinus canicula; Chondrichthyes), we observed differential immunostaining of the cardiac segments using another pan-MyHC, the A4.1025 antibody. In order to investigate the relevance of this finding for better understanding of the morphology and evolution of the vertebrate heart, we performed immunohistochemistry, slot blot and western blot in several species of chondrichthyans, actinopterygians and mammals using the above mentioned antibodies. In the dogfish heart, A4.1025 and MF20 specifically recognized MyHC isoforms, although with different degree of affinity. MF20 reactivity was homogeneous and high in all the myocardial segments. However, A4.1025 reactivity was heterogeneous. It was high in the sinus venosus (external layer), atrium and atrioventricular region, low in the ventricle and conus arteriosus, and null in the internal layer of the sinus venosus. A heterogeneous pattern of A4.1025 immunoreactivity was also detected in two other elasmobranchs, a holocephalan, a polypteryform and an acipenseriform. In all of these species, MF20 immunoreactivity was homogeneous. In addition, both markers showed a homogeneous immunoreactivity pattern in teleosts and mammals. Our results indicate that in the hearts of ancient gnathostomes, in all of which a conspicuous conus arteriosus exists, one or more MyHC isoforms with low affinity for A4.1025 show segment-specific distributions. Thus, A4.1025 appears to be an appropriated marker to identify the cardiac segments and their boundaries. We propose that the segmentspecific distribution of MyHC isoforms may generate a particular type of myocardial contractility associated with the presence of a conus arteriosus.

Technological, institutional and market structure changes as evolutionary processes: the case of the Port Wine sector (1680-1974).

Doutoramento em Economia.

An updated evolutionary classification of CRISPR–Cas systems

The evolution of CRISPR–cas loci, which encode adaptive immune systems in archaea and bacteria, involves rapid changes, in particular numerous rearrangements of the locus architecture and horizontal transfer of complete loci or individual modules. These dynamics complicate straightforward phylogenetic classification, but here we present an approach combining the analysis of signature protein families and features of the architecture of cas loci that unambiguously partitions most CRISPR–cas loci into distinct classes, types and subtypes. The new classification retains the overall structure of the previous version but is expanded to now encompass two classes, five types and 16 subtypes. The relative stability of the classification suggests that the most prevalent variants of CRISPR–Cas systems are already known. However, the existence of rare, currently unclassifiable variants implies that additional types and subtypes remain to be characterized.

Evolutionary transition to freshwater by ancestral marine palaemonids: evidence from osmoregulation in a tide pool shrimp

The transition from marine/brackish waters to freshwater habitats constitutes a severe osmotic and ionic challenge, and successful invasion has demanded the selection of morphological, physiological, biochemical and behavioral adaptations. We evaluated short-term (1 to 12 h exposure) and long-term (5 d acclimation), anisosmotic extracellular (osmolality, [Na(+), Cl(-)]) and long-term isosmotic intracellular osmoregulatory capability in Palaemon northropi, a neotropical intertidal shrimp. F northropi survives well and osmo- and ionoregulates strongly during short- and long-term exposure to 5-45 parts per thousand salinity, consistent with its rocky tide pool habitat subject to cyclic salinity fluctuations, Muscle total free amino acid (FAA) concentrations decreased by 63% in shrimp acclimated to 5%. salinity, revealing a role in hypoosmotic cell volume regulation; this decrease is mainly a consequence of diminished glycine, arginine and proline. Total FAA contributed 31% to muscle intracellular osmolality at 20 parts per thousand, an isosmotic salinity, and decreased to 13% after acclimation to 5 parts per thousand. Gill and nerve tissue FAA concentrations remained unaltered. These tissue-specific responses reflect efficient anisosmotic and anisoionic extracellular regulatory mechanisms, and reveal the dependence of muscle tissue on intracellular osmotic effectors. FAA concentration is higher in P. northropi than in diadromous and hololimnetic palaemonids, confirming muscle FAA concentration as a good parameter to evaluate the degree of adaptation to dilute media. The osmoregulatory capability of P. northropi may reflect the potential physiological capacity of ancestral marine palaemonids to penetrate into dilute media, and reveals the importance of evaluating osmoregulatory processes in endeavors to comprehend the invasion of dilute media by ancestral marine crustaceans.

Epidemiological and evolutionary inference of the transmission network of the 2014 highly pathogenic Avian Influenza H5N2 outbreak in British Columbia, Canada

The first North American outbreak of highly pathogenic avian influenza (HPAI) involving a virus of Eurasian A/goose/Guangdong/1/1996 (H5N1) lineage began in the Fraser Valley of British Columbia, Canada in late November 2014. A total of 11 commercial and 1 non-commercial (backyard) operations were infected before the outbreak was terminated. Control measures included movement restrictions that were placed on a total of 404 individual premises, 150 of which were located within a 3 km radius of an infected premise(s) (IP). A complete epidemiological investigation revealed that the source of this HPAI H5N2 virus for 4 of the commercial IPs and the single non-commercial IP likely involved indirect contact with wild birds. Three IPs were associated with the movement of birds or service providers and localized/environmental spread was suspected as the source of infection for the remaining 4 IPs. Viral phylogenies, as determined by Bayesian Inference and Maximum Likelihood methods, were used to validate the epidemiologically inferred transmission network. The phylogenetic clustering of concatenated viral genomes and the median-joining phylogenetic network of the viruses supported, for the most part, the transmission network that was inferred by the epidemiologic analysis.

Male sexual behaviour and ethanol consumption from an evolutionary perspective: a comment on "Sexual deprivation increases ethanol intake in Drosophila"

Shohat-Ophir et al. (1) demonstrate a connection between sexual behaviour and ethanol consumption in male Drosophila flies, and how the neuropeptide F system regulates ethanol preference. Their results are rightly discussed only in a physiological context, but this has facilitated erroneous anthropomorphic interpretations by the media. Here we discuss the link between male sexual behaviour and ethanol consumption from an evolutionary perspective, providing a broader context to interpret their results.

Reassessing the Evolutionary History of the 17q21 Inversion Polymorphism

A polymorphic inversion that lies on chromosome 17q21 comprises two major haplotype families (H1 and H2) that not only differ in orientation but also in copy-number. Although the processes driving the spread of the inversion-associated lineage (H2) in humans remain unclear, a selective advantage has been proposed for one of its subtypes. Here, we genotyped a large panel of individuals from previously overlooked populations using a custom array with a unique panel of H2-specific single nucleotide polymorphisms and found a patchy distribution of H2 haplotypes in Africa, with North Africans displaying a higher frequency of inverted subtypes, when compared with Sub-Saharan groups. Interestingly, North African H2s were found to be closer to "non-African" chromosomes further supporting that these populations may have diverged more recently from groups outside Africa. Our results uncovered higher diversity within the H2 family than previously described, weakening the hypothesis of a strong selective sweep on all inverted chromosomes and suggesting a rather complex evolutionary history at this locus.

What are we missing about marine invasions? Filling in the gaps with evolutionary genomics

Research on invasion biology has been largely dominated by studies on the ecological effects of invasion events, although recently, evolutionary processes have been shown to be important to invasion success. This is largely attributed to novel genomic tools that provide new opportunities to unravel the natural history, taxonomy, and invasion pathways of invasive species, as well as the genetic basis of adaptive traits that allow them to expand within and beyond their native range. Despite these advances and the growing literature of genomic research on terrestrial pests, these tools have not been widely applied to marine invasive species. This is in part due to the perception that high levels of dispersal and connectivity in many invasive marine species can limit the opportunity for local adaptation. However, there is growing evidence that even in species with high dispersal potential, significant site-specific adaptation can occur. We review how these “omic” tools provide unprecedented opportunities to characterise the role of adaptive variation, physiological tolerance, and epigenetic processes in determining the success of marine invaders. Yet, rapid range expansion in invasions can confound the analysis of genomic data, so we also review how data should be properly analysed and carefully interpreted under such circumstances. Although there are a limited number of studies pioneering this research in marine systems, this review highlights how future studies can be designed to integrate ecological and evolutionary information. Such datasets will be imperative for the effective management of marine pests.

Transmissible cancers in an evolutionary context.

Cancer is an evolutionary and ecological process in which complex interactions between tumour cells and their environment share many similarities with organismal evolution. Tumour cells with highest adaptive potential have a selective advantage over less fit cells. Naturally occurring transmissible cancers provide an ideal model system for investigating the evolutionary arms race between cancer cells and their surrounding micro-environment and macro-environment. However, the evolutionary landscapes in which contagious cancers reside have not been subjected to comprehensive investigation. Here, we provide a multifocal analysis of transmissible tumour progression and discuss the selection forces that shape it. We demonstrate that transmissible cancers adapt to both their micro-environment and macro-environment, and evolutionary theories applied to organisms are also relevant to these unique diseases. The three naturally occurring transmissible cancers, canine transmissible venereal tumour (CTVT) and Tasmanian devil facial tumour disease (DFTD) and the recently discovered clam leukaemia, exhibit different evolutionary phases: (i) CTVT, the oldest naturally occurring cell line is remarkably stable; (ii) DFTD exhibits the signs of stepwise cancer evolution; and (iii) clam leukaemia shows genetic instability. While all three contagious cancers carry the signature of ongoing and fairly recent adaptations to selective forces, CTVT appears to have reached an evolutionary stalemate with its host, while DFTD and the clam leukaemia appear to be still at a more dynamic phase of their evolution. Parallel investigation of contagious cancer genomes and transcriptomes and of their micro-environment and macro-environment could shed light on the selective forces shaping tumour development at different time points: during the progressive phase and at the endpoint. A greater understanding of transmissible cancers from an evolutionary ecology perspective will provide novel avenues for the prevention and treatment of both contagious and non-communicable cancers.

The evolutionary ecology of transmissible cancers.

Transmissible tumours, while rare, present a fascinating opportunity to examine the evolutionary dynamics of cancer as both an infectious agent and an exotic, invasive species. Only three naturally-occurring transmissible cancers have been observed so far in the wild: Tasmanian devil facial tumour diseases, canine transmissible venereal tumour, and clam leukaemia. Here, we define four conditions that are necessary and sufficient for direct passage of cancer cells between either vertebrate or invertebrate hosts. Successful transmission requires environment and behaviours that facilitate transfer of tumour cells between hosts including: tumour tissue properties that promote shedding of large numbers of malignant cells, tumour cell plasticity that permits their survival during transmission and growth in a new host, and a 'permissible' host or host tissue. This rare confluence of multiple host- and tumour cell-traits both explains the rarity of tumour cell transmission and provides novel insights into the dynamics that both promote and constrain their growth.