Mello, B. | Search bioRxiv

bioRxiv2017

Deciphering the regulation mechanism in biochemical networks by a systems-biology approach

To decipher molecular mechanisms in biological systems from system-level input-output data is challenging especially for complex processes that involve interactions among multiple components. Here, we study regulation of the multi-domain (P1-5) histidine kinase CheA by the MCP chemoreceptors. We develop a network model to describe dynamics of the system treating the receptor complex with CheW and P3P4P5 domains of CheA as a regulated enzyme with two substrates, P1 and ATP. The model enables us to search the hypothesis space systematically for the simplest possible regulation mechanism consistent with the available data. Our analysis reveals a novel dual regulation mechanism wherein besides regulating ATP binding the receptor activity has to regulate one other key reaction, either P1 binding or phosphotransfer between P1 and ATP. Furthermore, our study shows that the receptors only control kinetic rates of the enzyme without changing its equilibrium properties. Predictions are made for future experiments to distinguish the remaining two dual-regulation mechanisms. This systems-biology approach of combining modeling and a large input-output data-set should be applicable for studying other complex biological processes.

systems biology↗

bioRxiv2017

Multispecies coalescent analysis unravels the non-monophyly and controversial relationships of Hexapoda

With the increase in the availability of genomic data, sequences from different loci are usually concatenated in a supermatrix for phylogenetic inference. However, as an alternative to the supermatrix approach, several implementations of the multispecies coalescent (MSC) have been increasingly used in phylogenomic analyses due to their advantages in accommodating gene tree topological heterogeneity by taking account population-level processes. Moreover, the development of faster algorithms under the MSC is enabling the analysis of thousands of loci/taxa. Here, we explored the MSC approach for a phylogenomic dataset of Insecta. Even with the challenges posed by insects, due to large effective population sizes coupled with short deep internal branches, our MSC analysis could recover several orders and evolutionary relationships in agreement with current insect systematics. However, some phylogenetic relationships were not recovered by MSC methods. Most noticeable, a remiped crustacean was positioned within the Insecta. Additionally, the interordinal relationships within Polyneoptera and Neuropteroidea contradicted recent works, by suggesting the non-monophyly of Neuroptera. We notice, however, that these phylogenetic arrangements were also poorly supported by previous analyses and that they were sensitive to gene sampling.

evolutionary biology↗