Properties of selected mutations and genotypic landscapes under Fisher's Geometric Model

The fitness landscape - the mapping between genotypes and fitness - determines properties of the process of adaptation. Several small genetic fitness landscapes have recently been built by selecting a handful of beneficial mutations and measuring fitness of all combinations of these mutations. Here we generate several testable predictions for the properties of these landscapes under Fisher's geometric model of adaptation (FGMA). When far from the fitness optimum, we analytically compute the fitness effect of beneficial mutations and their epistatic interactions. We show that epistasis may be negative or positive on average depending on the distance of the ancestral genotype to the optimum and whether mutations were independently selected or co-selected in an adaptive walk. Using simulations, we show that genetic landscapes built from FGMA are very close to an additive landscape when the ancestral strain is far from the optimum. However, when close to the optimum, a large diversity of landscape with substantial ruggedness and sign epistasis emerged. Strikingly, landscapes built from different realizations of stochastic adaptive walks in the same exact conditions were highly variable, suggesting that several realizations of small genetic landscapes are needed to gain information about the underlying architecture of the global adaptive landscape.Comment: 51 pages, 8 figure

Decomposing the site frequency spectrum: the impact of tree topology on neutrality tests

We investigate the dependence of the site frequency spectrum (SFS) on the topological structure of genealogical trees. We show that basic population genetic statistics - for instance estimators of $\theta$ or neutrality tests such as Tajima's $D$ - can be decomposed into components of waiting times between coalescent events and of tree topology. Our results clarify the relative impact of the two components on these statistics. We provide a rigorous interpretation of positive or negative values of an important class of neutrality tests in terms of the underlying tree shape. In particular, we show that values of Tajima's $D$ and Fay and Wu's $H$ depend in a direct way on a peculiar measure of tree balance which is mostly determined by the root balance of the tree. We present a new test for selection in the same class as Fay and Wu's $H$ and discuss its interpretation and power. Finally, we determine the trees corresponding to extreme expected values of these neutrality tests and present formulae for these extreme values as a function of sample size and number of segregating sites.Comment: 23 pages, 8 figure

Sénescence, sélection sexuelle et dynamique de population du bouquetin des Alpes (Capra Ibex)

Le principal objectif de cette thèse est d’étudier les variations intra et inter individuelle pour deux traits phénotypiques reliés à la valeur sélective, et d’analyser la dynamique d’une population sauvage de bouquetin des Alpes (Capra ibex). Le premier chapitre analyse la relation de deux traits phénotypiques reliés à la valeur sélective (le gain de masse corporelle, et l’intensité d’infection parasitaire gastro-intestinal) et d’un caractère sexuel secondaire (la croissance des cornes) avec l’âge, des facteurs environnementaux, la survie, et avec l’hétérozygotie, ceci au sein d’un large échantillon de bouquetins des Alpes mâles en libertés et marqués individuellement. À travers la croissance corporelle et les comptages fécaux d’oeufs de nématodes gastro-intestinaux, il a été mis en évidence un phénomène de sénescence et de coût pour la reproduction. En analysant un large échantillon de squelettes de bouquetins mâles trouvés morts dans l’hiver pour cause de famine, nous avons trouvé que le début de la sénescence était caractérisé par la longueur de segments de croissance annuels âges spécifiques des cornes, mais pas par leur asymétrie. Enfin, des corrélations entre l’hétérozygotie et la valeur sélective ont été mises en évidence pour la croissance des cornes, mais pas pour la masse corporelle et l’intensité d’infection parasitaire. Le deuxième chapitre traite de l’importance relative de la densité dépendance et de la variabilité stochastique du climat sur la dynamique d’une population d’ongulé de montagne, à travers l’analyse de série temporelle de 45 ans de recensements de bouquetins des Alpes collectés dans le Parc National du Grand Paradis en Italie. Pendant les 28 premières années de l’étude, le nombre total de bouquetins a varié entre 2600 et 4000 sans tendance visuelle apparente. Au cours de cette période, il est apparu que des oscillations avec une périodicité de 3 à 8 ans étaient présentes. Dès 1982, les comptages de bouquetin ont augmentés régulièrement pour atteindre un pic de 5000 en 1993 et ensuite décroître. Nous avons montré que la taille de population du bouquetin était limitée à la fois par la densité dépendance et par l’épaisseur de neige. Un modèle basé sur ces deux facteurs et ajusté pour les 19 premières années de données, réussi avec succès à prédire l’augmentation et le déclin subséquent de la taille totale de la population pour les 20 dernières années de l’étude. Cette thèse conclue avec un troisième chapitre présentant deux techniques innovatrices utiles pour l’étude de populations d’ongulés en liberté.Abstract: The main objectives of this thesis are to investigate within and between-individual variation in fitness related phenotypic traits and to analyse the population dynamics of a wild population of Alpine ibex (Capra ibex). The first chapter analyzes the relationship of two fitness-related phenotypic traits (body mass gain and the intensity of gastrointestinal parasite infection) and one secondary sexual trait (horn growth) with age, environmental factors, survival and heterozygosity in a large sample of individually tagged free-ranging Alpine ibex males. Evidence for senescence and costs of reproduction in body growth and fecal counts of gastrointestinal nematode eggs was found. Analysing a large sample of male ibex skulls, found dead in winter from starvation, we found that the onset of senescence was signaled by the length of age specific yearly horn growth segments, but not by their asymmetry. Finally evidence for heterozygosity-fitness correlations was found for horn growth, but not for body mass and the intensity of parasite infection. The second chapter investigates the relative importance of density dependence and of stochastic climatic variability in the population dynamics of a mountain ungulate, analysing a 45 year long time series of Alpine ibex censuses collected in the Gran Paradiso National Park, Italy During the first 28 years of the study, the total number of ibex ranged from about 2600 to about 4000 with no visually apparent trend. During this period oscillations with periodicities of about 3 and 8 years appeared to be present. From 1982 onwards, ibex counts increased steadily and peaked at almost 5000 in 1993, decreasing afterwards. We show that the ibex population size was limited by both density dependence and deep snow. A model based on these factors fit to the first 19 years of data was successful in forecasting the increase and subsequent decline in total population size over the final 20 years of the study. The thesis concludes with a third chapter presenting two innovative techniques useful in the study of free-ranging populations of ungulates

The expected neutral frequency spectrum of linked sites

We present an exact, closed expression for the expected neutral Site Frequency Spectrum for two neutral sites, 2-SFS, without recombination. This spectrum is the immediate extension of the well known single site $\theta/f$ neutral SFS. Similar formulae are also provided for the case of the expected SFS of sites that are linked to a focal neutral mutation of known frequency. Formulae for finite samples are obtained by coalescent methods and remarkably simple expressions are derived for the SFS of a large population, which are also solutions of the multi-allelic Kolmogorov equations. Besides the general interest of these new spectra, they relate to interesting biological cases such as structural variants and introgressions. As an example, we present the expected neutral frequency spectrum of regions with a chromosomal inversion.Comment: 26 pages, 5 figure

Novel insights into RNAi off-target effects using C. elegans paralogs

<p>Abstract</p> <p>Background</p> <p>In the few years since its discovery, RNAi has turned into a very powerful tool for the study of gene function by allowing post-transcriptional gene silencing. The RNAi mechanism, which is based on the introduction of a double-stranded RNA (dsRNA) trigger whose sequence is similar to that of the targeted messenger RNA (mRNA), is subject to off-target cross-reaction.</p> <p>Results</p> <p>We use a novel strategy based on phenotypic analysis of paralogs and predict that, in <it>Caenorhabditis elegans</it>, off-target effects occur when an mRNA sequence shares more than 95% identity over 40 nucleotides with the dsRNA. Interestingly, our results suggest that the minimum length necessary of a high-similarity stretch between a dsRNA and its target in order to observe an efficient RNAi effect varies from 30 to 50 nucleotides rather than 22 nucleotides, which is the length of siRNAs in <it>C. elegans</it>.</p> <p>Conclusion</p> <p>Our predictive methods would improve the design of dsRNA and ultimately the use of RNAi as a therapeutic tool upon experimental verification.</p

Predicting the potential distribution of the Endangered huemul deer Hippocamelus bisulcus in North Patagonia

Habitat loss is one of the main threats to wildlife, particularly large mammals. Estimating the potential distribution of threatened species to guide surveys and conservation is crucial, primarily because such species tend to exist in small fragmented populations. The Endangered huemul deer Hippocamelus bisulcus is endemic to the southern Andes of Chile and Argentina. Although the species occurs in the Valdivian Ecoregion, a hotspot for biodiversity, we have no information on its occupancy and potential distribution in this region. We built and compared species distribution models for huemul using the maximum entropy approach, using 258 presence records and sets of bioclimatic and geographical variables as predictors, with the objective of assessing the potential distribution of the species in the Valdivian Ecoregion. Annual temperature range and summer precipitation were the predictive variables with the greatest influence in the best-fitting model. Approximately 12,360 km2 of the study area was identified as suitable habitat for the huemul, of which 30% is included in the national protected area systems of Chile and Argentina. The map of potential distribution produced by our model will facilitate prioritization of future survey efforts in other remote and unexplored areas in which huemul have not been recorded since the 1980s, but where there is a high probability of their occurrence

Flight Initiation Distance and Starting Distance: Biological Effect or Mathematical Artefact?

In many studies, flight initiation distance (FID, the distance at which a prey starts to flee at the approach of a walker) is positively related to starting distance (SD, the distance at which the walker begins to approach) and alert distance (AD, the distance at which the focal individual becomes alert to the threat). In spite of the fundamental differences between SD, a covariate that may not have any biological effect, and AD, a measure related to the behaviour of the animal, it is common to use SD as a proxy for AD when AD is hard to measure (e.g. in species that do not exhibit distinguishable alert postures). However, the relationship between SD and AD or FID may not have any biological reasons, but may instead simply result from a mathematical artefact because of the constraints SD = AD = FID. Under such constrains, the homoscedasticity assumption is violated, and thus, the classical null hypothesis of linear regression (slope = 0) is invalid. In this study, we first show that using SD as a proxy for AD can strongly affect the results on FID. Using data from FID tests on alpine marmots (Marmota marmota), a linear mixed model with AD as a covariate, suggested that the interaction between previous activity and AD had an effect on FID, while this effect was not detected when SD replaced AD as the covariate in the analysis. We then propose that the actual statistical test of the relationship between SD, AD and FID should be based on a null hypothesis that incorporates the constraint SD = AD = FID = 0 and generate 95% CI of simulated slopes obtained from random values under this constraint. This null hypothesis can be rejected if the observed slope of the relationship between two of these variables is outside the 95% CI. We demonstrated that, for alpine marmots, the observed slope of the relationship between AD and SD was within the 95% CI of the simulated slopes. The absence of a statistically significant biological effect in the relationship between SD and AD raises important questions on the outcome of relationship between SD and FID. In Alpine marmot flight, decision should be studied separating the effect of SD on AD and the effect of AD on FID

Monitoring wildlife population trends with sample counts: a case study on the Alpine ibex (Capra ibex)

Monitoring population dynamics is of fundamental importance in conservation but assessing trends in abundance can be costly, especially in large and rough areas. Obtaining trend estimations from counts performed in only a portion of the total area (sample counts) can be a cost‐effective method to improve the monitoring and conservation of species difficult to count.We tested the effectiveness of sample counts in monitoring population trends of wild animals, using as a model population the Alpine ibex Capra ibex in the Gran Paradiso National Park (Italy), both with computer simulations and using historical count data collected over the last 65 years. Despite sample counts failed to correctly estimate the true population abundance, sampling half of the target area could reliably monitor the trend of the target population. In case of strong changes in abundance, an even lower proportion of the total area could be sufficient to identify the direction of the population trend. However, when there is a high yearly trend variability, the required number of samples increases and even counting in the entire area can be ineffective to detect population trends. The effect of other parameters, such as which portion of the area is sampled and detectability, was lower, but these should be tested case by case.Sample counts could therefore constitute a viable alternative to assess population trends, allowing for important, cost‐effective improvements in the monitoring of wild animals of conservation interest

Early onset of vegetation growth vs. rapid green-up : impacts on juvenile mountain ungulates

Seasonal patterns of climate and vegetation growth are expected to be altered by global warming. In alpine environments, the reproduction of birds and mammals is tightly linked to seasonality; therefore such alterations may have strong repercussions on recruitment. We used the normalized difference vegetation index (NDVI), a satellite-based measurement that correlates strongly with aboveground net primary productivity, to explore how annual variations in the timing of vegetation onset and in the rate of change in primary production during green-up affected juvenile growth and survival of bighorn sheep (Ovis canadensis), Alpine ibex (Capra ibex), and mountain goats (Oreamnos americanus) in four different populations in two continents. We indexed timing of onset of vegetation growth by the integrated NDVI (INDVI) in May. The rate of change in primary production during green-up (early May to early July) was estimated as (1) the maximal slope between any two successive bimonthly NDVI values during this period and (2) the slope in NDVI between early May and early July. The maximal slope in NDVI was negatively correlated with lamb growth and survival in both populations of bighorn sheep, growth of mountain goat kids, and survival of Alpine ibex kids, but not with survival of mountain goat kids. There was no effect of INDVI in May and of the slope in NDVI between early May and early July on juvenile growth and survival for any species. Although rapid changes in NDVI during the green-up period could translate into higher plant productivity, they may also lead to a shorter period of availability of high-quality forage over a large spatial scale, decreasing the opportunity for mountain ungulates to exploit high-quality forage. Our results suggest that attempts to forecast how warmer winters and springs will affect animal population dynamics and life histories in alpine environments should consider factors influencing the rate of changes in primary production during green-up and the timing of vegetation onset