CD44 is a membrane-bound extracellular matrix (ECM) receptor interacting, among others, with hyaluronic acid (HA) and osteopontin (OPN). Cancer progression and metastasis are greatly influenced by the cancer micro-environment, consisting of ECM, immune cells and cancer-associated fibroblasts (CAF). Recruitment of fibroblasts (FB) into the role as CAFs is caused by paracrine signals from the tumor, including TGFb1, PDGF and OPN. The effect of OPN on the transformation of FB into CAF is mediated by...
Motivation: Despite the importance of gene regulatory enhancers in human biology and evolution, we lack a comprehensive evolutionary model of enhancer sequence architecture and function. This substantially limits our understanding of the genetic basis for divergence between species and our ability to interpret the effects of non-coding variants on human traits. Results: To explore enhancer sequence evolution and its relationship to regulatory function, we traced the evolutionary origins of human...
We derive how directional and disruptive selection operate on scalar traits in heterogeneous group-structured populations for a general class of models. In particular, we assume that each group in the population can be in one of a finite number of states, where states can affect group size and/or other environmental variables, at a given time. Using up to second-order perturbation expansions of the invasion fitness of a mutant allele, we derive expressions for the directional and disruptive selection...
Populations are shaped by their history. Therefore, it is crucial to interpret population structure in an evolutionary context. Wright FST measures current population structure, whereas population-specific FST measures deviation from the ancestral population. To understand current population structure and a population history of range expansion, we propose a novel representation method that overlays population-specific FST estimates on an unrooted neighbor-joining tree inferred from a pairwise FST...
Background: Parasites of the order Trypanosomatida are known due to their medical relevance. Trypanosomes cause African sleeping sickness and Chagas disease in South America, and Leishmania ROSS, 1903 species mutilate and kill hundreds of thousands of people each year. However, human pathogens are very few when compared to the great diversity of trypanosomatids. Despite the progresses made in the past decades on understanding the evolution of this group of organisms, there are still many open questions...
Diptera is a megadiverse group of flies with sophisticated chemical detection systems, which exploits an incredible variety of ecological niches. Among the vast array of odorants in natural environments, indoles stand out as playing crucial roles in mediating fly behavior. In mosquitoes, indolic compounds are detected by an ancient class of conserved indolergic Odorant Receptors (indolORs). In this study, we have identified a set of 92 putative indolOR genes encoded in the genomes of Nematoceran...
The evolutionary pressures that determine the location (chromosomal or plasmid-borne) of bacterial genes are not fully understood. We investigate these pressures through mathematical modelling in the context of antibiotic resistance, which is often found on plasmids. Our central finding is that gene location is under positive frequency-dependent selection, which can keep moderately beneficial genes on plasmids, despite occasional plasmid loss. For these genes, positive frequency-dependence leads...
Phylogenetic trees are currently routinely reconstructed from an alignment of character sequences (usually nucleotide sequences). Bayesian tools, such as MrBayes, RevBayes and BEAST2, have gained much popularity over the last decade, as they allow joint estimation of the posterior distribution of the phylogenetic trees and the parameters of the underlying inference model. An important ingredient of these Bayesian approaches is the species tree prior. In principle, the Bayesian framework allows for...
The origin of plastids was a major evolutionary event that paved the way for an astonishing diversification of photosynthetic eukaryotes. Plastids originated by endosymbiosis between a heterotrophic eukaryotic host and a cyanobacterium, presumably in a common ancestor of all primary photosynthetic eukaryotes (Archaeplastida). A single origin of primary plastids is well supported by plastid evidence but not by nuclear phylogenomic analyses, which have consistently failed to recover the monophyly of...
Genome studies of facultative sexual species, which can either reproduce sexually or asexually, are providing insight into the evolutionary consequences of mixed reproductive modes. It is currently unclear to what extent the evolutionary history of facultative sexuals' genomes can be approximated by the standard coalescent, and if a coalescent effective population size Ne exists. Here, I determine if and when these approximations can be made. When sex is frequent (occurring at a frequency much greater...
Motivation: Despite the importance of gene regulatory enhancers in human biology and evolution, we lack a comprehensive evolutionary model of enhancer sequence architecture and function. This substantially limits our understanding of the genetic basis for divergence between species and our ability to interpret the effects of non-coding variants on human traits. Results: To explore enhancer sequence evolution and its relationship to regulatory function, we traced the evolutionary origins of human...
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