On the accumulation of deleterious mutations during range expansions

We investigate the effect of spatial range expansions on the evolution of fitness when beneficial and deleterious mutations co-segregate. We perform individual-based simulations of a uniform linear habitat and complement them with analytical approximations for the evolution of mean fitness at the edge of the expansion. We find that deleterious mutations accumulate steadily on the wave front during range expansions, thus creating an expansion load. Reduced fitness due to the expansion load is not restricted to the wave front but occurs over a large proportion of newly colonized habitats. The expansion load can persist and represent a major fraction of the total mutation load thousands of generations after the expansion. Our results extend qualitatively and quantitatively to two-dimensional expansions. The phenomenon of expansion load may explain growing evidence that populations that have recently expanded, including humans, show an excess of deleterious mutations. To test the predictions of our model, we analyze patterns of neutral and non-neutral genetic diversity in humans and find an excellent fit between theory and data

Mathematical models of frequency-dependent selection with dominance

In dieser Dissertation präsentiere ich Teile meiner wissenschaftlichen Arbeit über mathematische Modelle in der Populationsgenetik. Die Dissertation besteht aus zwei Teilen welche sich beide mit frequenzabhängiger Selektion und Dominanz beschäftigen. Im ersten Teil betrachte ich ein Modell mit innerspezifischer Kompetition und assortativer Paarung. Dieser Teil besteht aus zwei eng miteinander verbundenen Kapiteln. Im ersten Kapitel wird die Evolution von Dominanz unter assortativer Paarung analysiert. Kapitel Zwei behandelt die Evolution von assortativer Paarung mit einem konstanten Grad von Dominanz. Diese Arbeit baut auf meiner Diplomarbeit auf in welcher ich die Evolution von Dominanz unter frequenzabhängiger Selektion in einer sich zufällig paarenden Population studiert habe. Teil zwei der Dissertation besteht aus einem einzelnen Kapitel und behandelt eine andere Form von frequenzabhängiger Selektion. In diesem Kapitel analysiere ich den Zusammenhang zwischen dem Grad von Dominanz und der Anzahl der Allele die durch Selektion und Migration in zwei verschiedenen Lebensräumen erhalten werden können. Dieses Kapitel wurde durch einen kürzlich erschienenen Artikel von Professor Thomas Nagylaki motiviert.In this thesis, I present part of my work in my main research area, namely mathematical population genetics. The work presented here manifests two lines of research of mathematical models of frequency-dependent selection. Dominance and its effect on the maintenance of genetic variation and speciation spans the arch between the two parts. In the first part, we study a model of intraspecific competition and assortative mating. Part I consists of two articles that are closely linked to each other. In Chapter 1, we study the evolution of dominance in an assortatively mating population under frequency-dependent intraspecific competition. In Chapter 2, we keep dominance fixed and let assortment evolve. The initial motivation of the work presented in Part I is rooted in my master thesis, in which I studied the evolution of dominance under frequency-dependent selection in a randomly mating population. In the second part, a different class of models is studied. Part II consists of a single chapter in which we study the relationship between the degree of dominance and the number of alleles that can be maintained at a stable equilibrium in two demes. This work was motivated by a recent paper of Professor Thomas Nagylaki

Demographic history and genomic consequences of 10,000 generations of isolation in a wild mammal.

Increased human activities caused the isolation of populations in many species-often associated with genetic depletion and negative fitness effects. The effects of isolation are predicted by theory, but long-term data from natural populations are scarce. We show, with full genome sequences, that common voles (Microtus arvalis) in the Orkney archipelago have remained genetically isolated from conspecifics in continental Europe since their introduction by humans over 5,000 years ago. Modern Orkney vole populations are genetically highly differentiated from continental conspecifics as a result of genetic drift processes. Colonization likely started on the biggest Orkney island and vole populations on smaller islands were gradually split off, without signs of secondary admixture. Despite having large modern population sizes, Orkney voles are genetically depauperate and successive introductions to smaller islands resulted in further reduction of genetic diversity. We detected high levels of fixation of predicted deleterious variation compared with continental populations, particularly on smaller islands, yet the fitness effects realized in nature are unknown. Simulations showed that predominantly mildly deleterious mutations were fixed in populations, while highly deleterious mutations were purged early in the history of the Orkney population. Relaxation of selection overall due to benign environmental conditions on the islands and the effects of soft selection may have contributed to the repeated, successful establishment of Orkney voles despite potential fitness loss. Furthermore, the specific life history of these small mammals, resulting in relatively large population sizes, has probably been important for their long-term persistence in full isolation

The impact of genetic surfing on neutral genomic diversity.

Range expansions have been common in the history of most species. Serial founder effects and subsequent population growth at expansion fronts typically lead to loss of genomic diversity along the expansion axis. A frequent consequence is the phenomenon of "gene surfing", where variants located near the expanding front can reach high frequencies or even fix in newly colonized territories. Although gene surfing events have been characterized thoroughly for a specific locus, their effects on linked genomic regions and on the overall patterns of genomic diversity have been little investigated. In this study, we simulated the evolution of whole genomes during several types of 1D and 2D range expansions differing by the extent of migration, founder events and recombination rates. We focused on the characterization of local dips of diversity, or "troughs", taken as a proxy for surfing events. We find that, for a given recombination rate, once we consider the amount of diversity lost since the beginning of the expansion, it is possible to predict the initial evolution of trough density and their average width irrespectively of the expansion condition. Furthermore, when recombination rates vary across the genome, we find that troughs are over-represented in regions of low recombination. Therefore, range expansions can leave local and global genomic signatures often interpreted as evidence of past selective events. Given the generality of our results, they could be used as a null model for species having gone through recent expansions, and thus be helpful to correctly interpret many evolutionary biology studies

Randomized Controlled Trial of Thresholds for Drain Removal After Anatomic Lung Resection.

BACKGROUND The criteria for chest drain removal following lung resections remain vague and rely on personal experience instead of evidence. Since pleural fluid resorption is proportional to body weight, a weight-related approach seems reasonable. We examined the feasibility of a weight-adjusted fluid output threshold concerning postoperative respiratory complications and the occurrence of symptomatic pleural effusion after chest drain removal. Our secondary objectives were the length of hospital stay and the pain levels before and after chest drain removal. METHODS Single-center randomized controlled trial including 337 patients planned for open or thoracoscopic anatomical lung resections. Patients were randomized postoperatively into two groups. The chest drain was removed in the study group according to a fluid output threshold calculated by the 5 mL x body weight (in kg) / 24 hours formula. In the control group, our previous traditional fluid threshold of 200 mL/ 24 hours was applied. RESULTS No differences were evident regarding the occurrence of pleural effusion, dyspnea at discharge and 30 days postoperatively. In the logistic regression analysis, the surgical modality was a risk factor for other complications, and age was the only variable influencing postoperative dyspnea. Time to chest drain removal was identical in both groups, and time to discharge was shorter following open surgery in the test group. CONCLUSIONS No increased postoperative complications occurred with this weight-based formula, and a trend toward earlier discharge after open surgery was observed in the test group

Evolution of Assortative Mating in a Population Expressing Dominance

In this article, we study the influence of dominance on the evolution of assortative mating. We perform a population-genetic analysis of a two-locus two-allele model. We consider a quantitative trait that is under a mixture of frequency-independent stabilizing selection and density- and frequency-dependent selection caused by intraspecific competition for a continuum of resources. The trait is determined by a single (ecological) locus and expresses intermediate dominance. The second (modifier) locus determines the degree of assortative mating, which is expressed in females only. Assortative mating is based on similarities in the quantitative trait (‘magic trait’ model). Analytical conditions for the invasion of assortment modifiers are derived in the limit of weak selection and weak assortment. For the full model, extensive numerical iterations are performed to study the global dynamics. This allows us to gain a better understanding of the interaction of the different selective forces. Remarkably, depending on the size of modifier effects, dominance can have different effects on the evolution of assortment. We show that dominance hinders the evolution of assortment if modifier effects are small, but promotes it if modifier effects are large. These findings differ from those in previous work based on adaptive dynamics

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Dominance and the maintenance of polymorphism in multiallelic migration-selection models with two demes

The maintenance of genetic variation in a spatially heterogeneous environment has been one of the main research themes in theoretical population genetics. Despite considerable progress in understanding the consequences of spatially structured environments on genetic variation, many problems remain unsolved. One of them concerns the relationship between the number of demes, the degree of dominance, and the maximum number of alleles that can be maintained by selection in a subdivided population. In this work, we study the potential of maintaining genetic variation in a two-deme model with deme-independent degree of intermediate dominance, which includes absence of G x E interaction as a special case. We present a thorough numerical analysis of a two-deme three-allele model, which allows us to identify dominance and selection patterns that harbor the potential for stable triallelic equilibria. The information gained by this approach is then used to construct an example in which existence and asymptotic stability of a fully polymorphic equilibrium can be proved analytically. Noteworthy, in this example the parameter range in which three alleles can coexist is maximized for intermediate migration rates. Our results can be interpreted in a specialist-generalist context and (among others) show when two specialists can coexist with a generalist in two demes if the degree of dominance is deme independent and intermediate. The dominance relation between the generalist allele and the specialist alleles play a decisive role. We also discuss linear selection on a quantitative trait and show that G x E interaction is not necessary for the maintenance of more than two alleles in two demes

Strong neutral sweeps occurring during a population contraction

A strong reduction in diversity around a specific locus is often interpreted as a recent rapid fixation of a positively selected allele, a phenomenon called a selective sweep. Rapid fixation of neutral variants can however lead to similar reduction in local diversity, especially when the population experiences changes in population size, e.g., bottlenecks or range expansions. The fact that demographic processes can lead to signals of nucleotide diversity very similar to signals of selective sweeps is at the core of an ongoing discussion about the roles of demography and natural selection in shaping patterns of neutral variation. Here we quantitatively investigate the shape of such neutral valleys of diversity under a simple model of a single population size change, and we compare it to signals of a selective sweep. We analytically describe the expected shape of such “neutral sweeps” and show that selective sweep valleys of diversity are, for the same fixation time, wider than neutral valleys. On the other hand, it is always possible to parametrize our model to find a neutral valley that has the same width as a given selected valley. We apply our framework to the case of a putative selective sweep signal around the gene Quetzalcoatl in D. melanogaster and show that the valley of diversity in the vicinity of this gene is compatible with a short bottleneck scenario without selection. Our findings provide further insight in how simple demographic models can create valleys of genetic diversity that may falsely be attributed to positive selection

Range expansion and mutation load: insights from theoretical population genetics, experimental evolution and human genomics

Non UBCUnreviewedAuthor affiliation: University of BernPostdoctora