Conserved, ultraconserved and other classes of constrained non-coding elements (referred as CNEs) represent one of the mysteries of current comparative genomics. These elements are defined using various degrees of sequence similarity between organisms and several thresholds of minimal length and are often marked by extreme conservation that frequently exceeds the one observed for protein-coding sequences. We here explore the distribution of different classes of CNEs in entire chromosomes, in the human genome. We employ two complementary methodologies, the scaling of block entropy and box-counting, with the aim to assess fractal characteristics of different CNE datasets. Both approaches converge to the conclusion that well-developed fractality is characteristic of elements that are either marked by extreme conservation between two or more organisms or are of ancient origin, i.e. conserved between distant organisms across evolution. Given that CNEs are often clustered around genes, especially those that regulate developmental processes, we verify by appropriate gene masking that fractal-like patterns emerge irrespectively of whether elements found in proximity or inside genes are excluded or not. An evolutionary scenario is proposed, involving genomic events, that might account for fractal distribution of CNEs in the human genome as indicated through numerical simulations.
Evolution of complex phenotypes through successions of adaptive steps
Tin Y. Pang, Martin Lercher
The emergence of complex phenotype is a fascinating question of evolutionary biology, and we sought to understand preadaptation which facilitated the development of complex phenotypes, in the context of bacterial metabolic network. Genes coordinated for a phenotype are likely to cluster on the same place of the genome, which so allows horizontal gene transfer (HGT) to pass the phenotype to another bacterium. But for a complex phenotype, its genes are clustered on different places of the genome cannot be transferred adaptively; it is preadaptation, which refers to adaptive transfer of a segment relevant to a complex phenotype for other purposes, that allows it later to be recruited for the complex phenotype. To search for preadaptation in the evolutionary history of E. coli, we reconstructed the ancestral genomes from various strains, identified the transferred genes, grouped them into possible transferred segments, and analyzed the gains in nutritional phenotypes corresponding to the acquisitions of segments of metabolic genes. Properties of these HGT segments inferred from data are enumerated and compared with a model of HGT, which shows that: 1) HGT segments are likely to adaptive, and segments carrying reactions essential to phenotypic gains but non-adaptive are rare; 2) the landscape of segment transfer for complex phenotypes is directional and path-dependent; 3) cooperation between HGT segments to support various nutritional phenotypes are observed to be more frequent than expected, which serves as an evidence to preadaptation in the evolution of bacterial metabolic network.
Wolbachia infection in a sex-structured mosquito population carrying West Nile virus
József Z. Farkas, Stephen A. Gourley, Rongsong Liu, Abdul-Aziz Yakubu
Wolbachia is possibly the most studied reproductive parasite of arthropod species. It appears to be a promising candidate for biocontrol of some mosquito borne diseases. We begin by developing a sex-structured model for a Wolbachia infected mosquito population. Our model incorporates the key effects of Wolbachia infection including cytoplasmic incompatibility and male killing. We also allow the possibility of reduced reproductive output, incomplete maternal transmission, and different mortality rates for uninfected/infected male/female individuals. We study the existence and local stability of equilibria, including the biologically relevant and interesting boundary equilibria. For some biologically relevant parameter regimes there may be multiple coexistence steady states including, very importantly, a coexistence steady state in which Wolbachia infected individuals dominate. We also extend the model to incorporate West Nile virus (WNv) dynamics, using an SEI modelling approach. Recent evidence suggests that a particular strain of Wolbachia infection significantly reduces WNv replication in Aedes aegypti. We model this via increased time spent in the WNv-exposed compartment for Wolbachia infected female mosquitoes. A basic reproduction number R0 is computed for the WNv infection. Our results suggest that, if the mosquito population consists mainly of Wolbachia infected individuals, WNv eradication is likely if WNv replication in Wolbachia infected individuals is sufficiently reduced.
Algorithmic Methods to Infer the Evolutionary Trajectories in Cancer Progression
Giulio Caravagna, Alex Graudenzi, Daniele Ramazzotti, Rebeca Sanz-Pamplona, Luca De Sano, Giancarlo Mauri, Victor Moreno, Marco Antoniotti, Bud Mishra
The evolutionary nature of cancer relates directly to a renewed focus on the voluminous NGS (next generation sequencing) data, aiming at the identification of explanatory models of how the (epi)genomic events are choreographed in cancer initiation and development. However, despite the increasing availability of multiple additional -omics data, this quest has been frustrated by various theoretical and technical hurdles, mostly related to the dramatic heterogeneity and temporality of the disease. In this paper, we build on our recent works on selectivity relation among driver mutations in cancer progression and investigate their applicability to the modeling problem – both at the population and individual levels. On one hand, we devise an optimal, versatile and modular pipeline to extract ensemble-level progression models from cross-sectional sequenced cancer genomes. The pipeline combines state-of-the-art techniques for sample stratification, driver selection, identification of fitness-equivalent exclusive alterations and progression model inference. We demonstrate this pipeline’s ability to reproduce much of the current knowledge on colorectal cancer progression, as well as to suggest novel experimentally verifiable hypotheses. On the other hand, we prove that our framework can be applied, mutatis mutandis, in reconstructing the evolutionary history of cancer clones in single patients, as illustrated by an example with multiple biopsy data from clear cell renal carcinomas.
Handicap hypothesis implies emergence of dimorphic mating displays
Sara M. Clifton, Rosemary I. Braun, Daniel M. Abrams
Since 1975 Zahavi’s handicap principle has provided an elegant explanation for extravagant ornaments in the animal world: namely, that ornaments advertise fitness and must be costly in order to enforce honest signaling. Here, we show that populations of animals subject to the handicap principle may be forced to split into distinct subgroups of differing ornament size. We verify our claims via simple mathematical analysis and real-world data, including a composite data set of ornament size distributions from many distinct species, all of which are consistent with model predictions.