Horizontal gene transfer dynamics and distribution of fitness effects during microbial in silico evolution

<p>Abstract</p> <p>Background</p> <p>Horizontal gene transfer (HGT) is a process that facilitates the transfer of genetic material between organisms that are not directly related, and thus can affect both the rate of evolution and emergence of traits. Recent phylogenetic studies reveal HGT events are likely ubiquitous in the Tree of Life. However, our knowledge of HGT's role in evolution and biological organization is very limited, mainly due to the lack of ancestral evolutionary signatures and the difficulty to observe complex evolutionary dynamics in a laboratory setting. Here, we utilize a multi-scale microbial evolution model to comprehensively study the effect of HGT on the evolution of complex traits and organization of gene regulatory networks.</p> <p>Results</p> <p>Large-scale simulations reveal a distinct signature of the Distribution of Fitness Effect (DFE) for HGT events: during evolution, while mutation fitness effects become more negative and neutral, HGT events result in a balanced effect distribution. In either case, lethal events are significantly decreased during evolution (33.0% to 3.2%), a clear indication of mutational robustness. Interestingly, evolution was accelerated when populations were exposed to correlated environments of increasing complexity, especially in the presence of HGT, a phenomenon that warrants further investigation. High HGT rates were found to be disruptive, while the average transferred fragment size was linked to functional module size in the underlying biological network. Network analysis reveals that HGT results in larger regulatory networks, but with the same sparsity level as those evolved in its absence. Observed phenotypic variability and co-existing solutions were traced to individual gain/loss of function events, while subsequent re-wiring after fragment integration was necessary for complex traits to emerge.</p

Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach

We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases