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Biology subjects

Shikov, A. E.

Publications and source records attributed to Shikov, A. E..

2 recordsLinked to original sources

Recombine and succeed: a story of Cry toxins to expand the host range

BackgroundCry toxins are the most widely used sources of bioinsecticides in agriculture; therefore, improving their functionality requires a deep understanding of natural evolution. It is thought that Cry toxins emerge via domain III swapping, yet the underlying mechanism remains unclear. ResultsWe detected 50 recombination events using a dataset of 368 clusters representing a known diversity of Cry toxins using a computational analysis. Not only do domain swaps engage all the domains, but they also occur continuously with approximately 70% of toxins participating in domain exchanges. Once they happen, hybrid toxins face purifying selection pressure reflecting the advantageous nature of receiving novel domains. When these domain exchanges occur, their host specificity changes dramatically. Strains housing these loci are enriched with cry genes and can kill a broader spectrum of hosts, thus implying that recombination allows them to occupy novel niches. The respective recombination-affected cry genes are flanked with insertions and harbor highly conservative blocks between the domains borders suggesting that the genomic context governs the intra-domain recombination. ConclusionsOur study expands the established views of the role of recombination in the emergence of Cry toxins. Here, we demonstrate that the domain exchanges shape both Cry sequences, the composition of toxins in bacterial strains, and the sets of hosts affected. The collected data allowed us to propose a mechanism for how these toxins originate. Overall, the results suggest that domain exchanges have a profound impact on Cry toxins being a major evolutionary driver.

bioinformatics↗

Phenome-wide search for pleiotropic loci highlights key genes and molecular pathways for human complex traits

Over recent decades, genome-wide association studies (GWAS) have dramatically changed the understanding of human genetics. A recent genetic data release by UK Biobank has allowed many researchers worldwide to have comprehensive look into the genetic architecture of thousands of human phenotypes. In this study, we developed a novel statistical framework to assess phenome-wide significance and genetic pleiotropy across the human phenome based on GWAS summary statistics. We demonstrate widespread sharing of genetic architecture components between distinct groups of traits. Apart from known multiple associations inside the MHC locus, we discover high degree of pleiotropy for genes involved in immune system function, apoptosis, hemostasis cascades, as well as lipid and xenobiotic metabolism. We find several notable examples of novel pleiotropic loci (e.g., the MIR2113 microRNA broadly associated with cognition), and provide several possible mechanisms for these association signals. Our results allow for a functional phenome-wide look into the shared components of genetic architecture of human complex traits, and highlight crucial genes and pathways for their development.

genetics↗