Biology subjects

Foll, M.

Publications and source records attributed to Foll, M..

3 recordsLinked to original sources

bioRxiv2018

The fitness consequences of genetic variation in wild populations of mice

Adaptive evolution can occur when genetic change affects traits subject to natural selection. Although selection is a deterministic process, adaptation can be difficult to predict in finite populations because the functional connections between genotype, phenotype, and fitness are complex. Here, we make these connections using a combination of field and laboratory experiments. We conduct a large-scale manipulative field experiment with wild populations of deer mice in distinct habitats to directly estimate natural selection on pigmentation traits and next test whether this selection drives changes in allele frequency at an underlying pigment locus. We find that divergent cryptic phenotypes are repeatedly favoured in each habitat, leaving footprints of selection in the Agouti gene. Next, using transgenic experiments in Mus, we functionally test one of the Agouti mutations associated with survival, a Serine deletion in exon 2, and find that it causes lighter coat colour via changes in its protein binding properties. Finally, we show significant change in the frequency of this mutation in our field experiment. Together, our findings demonstrate how a sequence variant alters phenotype and show the ensuing ecological consequences that drive changes in population allele frequency, thereby revealing the full process of evolution by natural selection.

evolutionary biology↗

bioRxiv2018

Redefining mesothelioma types as a continuum uncovers the immune and vascular systems as key players in the diagnosis and prognosis of this disease

Malignant Pleural Mesothelioma (MPM) is an aggressive disease related to asbestos exposure, which incidence is expected to increase in the future, and with no effective therapeutic options. We have performed unsupervised analyses of publicly available RNAseq data for 297 MPM. We found that the molecular profile and the prognosis of this disease is better explained by a continuous model rather than by the current WHO classification into the epitheloid, biphasic and sarcomatoid histological types. The main source of variation of this continuum was explained by the immune and vascular pathways, with strong differences in the expression of pro-angiogenic genes and immune checkpoint inhibitors across samples. These data may inform future classifications of MPM and may also guide personalised therapeutic approaches for this disease.\n\nSignificanceMalignant Pleural Mesothelioma (MPM) is an aggressive disease with no effective therapeutic options. Unsupervised transcriptomic analyses of 297 MPM unveiled the vascular and the immune systems as key players in the prognosis of this disease, and identified potential therapeutic approaches for this disease targeting these pathways.

cancer biology↗

bioRxiv2017

The evolutionary history of Nebraska deer mice: local adaptation in the face of strong gene flow

The interplay of gene flow, genetic drift, and local selective pressure is a dynamic process that has been well studied from a theoretical perspective over the last century. Wright and Haldane laid the foundation for expectations under an island-continent model, demonstrating that an island-specific beneficial allele may be maintained locally if the selection coefficient is larger than the rate of migration of the ancestral allele from the continent. Subsequent extensions of this model have provided considerably more insight. Yet, connecting theoretical results with empirical data has proven challenging, owing to a lack of information on the relationship between genotype, phenotype, and fitness. Here, we examine the demographic and selective history of deer mice in and around the Nebraska Sand Hills, a system in which variation at the Agouti locus affects cryptic coloration that in turn affects the survival of mice in their local habitat. We first genotyped 250 individuals from eleven sites along a transect spanning the Sand Hills at 660,000 SNPs across the genome. Using these genomic data, we found that deer mice first colonized the Sand Hills following the last glacial period. Subsequent high rates of gene flow have served to homogenize the majority of the genome between populations on and off the Sand Hills, with the exception of the Agouti pigmentation locus. Furthermore, mutations at this locus are strongly associated with the pigment traits that are strongly correlated with local soil coloration and thus responsible for cryptic coloration.

evolutionary biology↗