Evolution of multicellularity by collective integration of spatial information

At the origin of multicellularity, cells may have evolved aggregation in response to predation, for functional specialisation or to allow large-scale integration of environmental cues. These group-level properties emerged from the interactions between cells in a group, and determined the selection pressures experienced by these cells. We investigate the evolution of multicellularity with an evolutionary model where cells search for resources by chemotaxis in a shallow, noisy gradient. Cells can evolve their adhesion to others in a periodically changing environment, where a cell's fitness solely depends on its distance from the gradient source. We show that multicellular aggregates evolve because they perform chemotaxis more efficiently than single cells. Only when the environment changes too frequently, a unicellular state evolves which relies on cell dispersal. Both strategies prevent the invasion of the other through interference competition, creating evolutionary bi-stability. Therefore, collective behaviour can be an emergent selective driver for undifferentiated multicellularity.Animal sciencesAnalysis and Stochastic

Twisting of the zebrafish heart tube during cardiac looping is a tbx5-dependent and tissue-intrinsic process

Organ laterality refers to the left-right asymmetry in disposition and conformation of internal organs and is established during embryogenesis. The heart is the first organ to display visible left-right asymmetries through its left-sided positioning and rightward looping. Here, we present a new zebrafish loss-of-function allele for tbx5a, which displays defective rightward cardiac looping morphogenesis. By mapping individual cardiomyocyte behavior during cardiac looping, we establish that ventricular and atrial cardiomyocytes rearrange in distinct directions. As a consequence, the cardiac chambers twist around the atrioventricular canal resulting in torsion of the heart tube, which is compromised in tbx5a mutants. Pharmacological treatment and ex vivo culture establishes that the cardiac twisting depends on intrinsic mechanisms and is independent from cardiac growth. Furthermore, genetic experiments indicate that looping requires proper tissue patterning. We conclude that cardiac looping involves twisting of the chambers around the atrioventricular canal, which requires correct tissue patterning by Tbx5a.Analysis and StochasticsAnimal science

Multilevel Evolution and the Emergence of Function

In this thesis we have researched how novel functions arise through Darwinian Evolution. Evolution has been generating novel traits, forms and functions since its inception, about four billion years ago. Cellular life did not exist at such an early evolutionary stage and instead, according to the RNA world hypothesis, RNAs functioned both as information storage medium (the role of DNA today) and as chemical reaction catalyst (the role of proteins). Because such RNAs catalysed each other's replication (i.e. replication is an altruistic trait), parasites that were replicated but did not spend any time replicating others should have been selected. Was the survival of replicators threatened by this? How could stronger replicators evolve if selection favoured parasites? In Chapter 2 we show that stronger parasites aid indirectly the evolution of stonger replicators thanks to a feedback process driven by the spatial self-organsation of the two species. The problem of the evolution of altruistic and cooperative traits is not limited to the RNA world, but extends to present day organisms as well. One example is the production of shared but costly, useful substances - so called public good - by many microorganisms. Selfish individuals that do not produce public good can thrive by exploiting cooperative individuals, but the system collapses if nobody produces public good. Should public good production be counter-selected when costs are larger because selection for selfishness intensifies? In Chapter 3 we show that selfish individuals evolve at higher costs and organise in space with cooperators. Spatial self-organisation feeds back on the evolution of public good production of cooperators, that become more cooperative, and selfish individuals, that become more selfish. In Chapter 4 we endow interacting RNA-like replicators with genotype and phenotype, respectively nucleotide sequence and secondary structure, and we study the evolutionary consequences of a complex genotype to phenotype map (RNA folding) at high mutation rates. We find that a functional ecosystem emerges, in which novel functions are associated to sequences that cannot be replicated. Such ecosystem enhances the survival of a single (master) sequence. In turn, this sequence contains the entire information to generate the functional ecosystem, and this information is decoded via the mutational process. The stabilising effect of mutations was experimentally observed in yeast's rRNA gene cluster, where mutations ensuing from transcription-replication conflicts are exploited to increase rRNA gene copy number depending on resource availability. In Chapter 5 we model yeast's rRNA mutational dynamics and find that larger rates of mutations are beneficial for long term genome integrity when they are biased towards gene duplications and deletions, even though their short term effect is near-neutral, as is the the case for yeast's rRNA. In conclusion, the results presented in this thesis highlight the merit of a multilevel approach for understanding evolution and its endless inventivity

Evaluation of oraquick® HIV-1/2 as oral rapid test

As Cameroon scales up its national HIV/AIDS control program, evaluating the performance of commercially available tests for accurate and cost effective diagnostics becomes essential. A cross-sectional study assessed the performance of an HIV oral rapid test. A total of 1520 participants consented to participate in the study. After counselling, they were tested for HIV using the national algorithm followed by OraQuick. Results of the national algorithm were compared to those of OraQuick, for sensitivity, specificity, positive predictive and negative predictive values. 62% of participants were male, and 1% was reported HIV-positive following the national algorithm. The OraQuick test had 93% sensitivity, 99% specificity, 99.93% NPV and 90% PPV (95% CI, Kappa 0.965). Though more expensive (2-6x) compared to the national algorithm tests, oral mucosal transudate-based test demonstrated good performance. Therefore, it could be implemented in resource constrained settings if subsidized and could increase participation since less invasive with no blood accident exposure

Towards evolutionary predictions: Current promises and challenges

Evolution has traditionally been a historical and descriptive science, and predicting future evolutionary processes has long been considered impossible. However, evolutionary predictions are increasingly being developed and used in medicine, agriculture, biotechnology and conservation biology. Evolutionary predictions may be used for different purposes, such as to prepare for the future, to try and change the course of evolution or to determine how well we understand evolutionary processes. Similarly, the exact aspect of the evolved population that we want to predict may also differ. For example, we could try to predict which genotype will dominate, the fitness of the population or the extinction probability of a population. In addition, there are many uses of evolutionary predictions that may not always be recognized as such. The main goal of this review is to increase awareness of methods and data in different research fields by showing the breadth of situations in which evolutionary predictions are made. We describe how diverse evolutionary predictions share a common structure described by the predictive scope, time scale and precision. Then, by using examples ranging from SARS-CoV2 and influenza to CRISPR-based gene drives and sustainable product formation in biotechnology, we discuss the methods for predicting evolution, the factors that affect predictability and how predictions can be used to prevent evolution in undesirable directions or to promote beneficial evolution (i.e. evolutionary control). We hope that this review will stimulate collaboration between fields by establishing a common language for evolutionary predictions

Towards evolutionary predictions: Current promises and challenges

Evolution has traditionally been a historical and descriptive science, and predicting future evolutionary processes has long been considered impossible. However, evolutionary predictions are increasingly being developed and used in medicine, agriculture, biotechnology and conservation biology. Evolutionary predictions may be used for different purposes, such as to prepare for the future, to try and change the course of evolution or to determine how well we understand evolutionary processes. Similarly, the exact aspect of the evolved population that we want to predict may also differ. For example, we could try to predict which genotype will dominate, the fitness of the population or the extinction probability of a population. In addition, there are many uses of evolutionary predictions that may not always be recognized as such. The main goal of this review is to increase awareness of methods and data in different research fields by showing the breadth of situations in which evolutionary predictions are made. We describe how diverse evolutionary predictions share a common structure described by the predictive scope, time scale and precision. Then, by using examples ranging from SARS-CoV2 and influenza to CRISPR-based gene drives and sustainable product formation in biotechnology, we discuss the methods for predicting evolution, the factors that affect predictability and how predictions can be used to prevent evolution in undesirable directions or to promote beneficial evolution (i.e. evolutionary control). We hope that this review will stimulate collaboration between fields by establishing a common language for evolutionary predictions