Modeling protein network evolution under genome duplication and domain shuffling

<p>Abstract</p> <p>Background</p> <p>Successive whole genome duplications have recently been firmly established in all major eukaryote kingdoms. Such <it>exponential </it>evolutionary processes must have largely contributed to shape the topology of protein-protein interaction (PPI) networks by outweighing, in particular, all <it>time-linear </it>network growths modeled so far.</p> <p>Results</p> <p>We propose and solve a mathematical model of PPI network evolution under successive genome duplications. This demonstrates, from first principles, that evolutionary conservation and scale-free topology are intrinsically linked properties of PPI networks and emerge from <it>i) </it>prevailing <it>exponential </it>network dynamics under duplication and <it>ii) asymmetric divergence </it>of gene duplicates. While required, we argue that this asymmetric divergence arises, in fact, spontaneously at the level of protein-binding sites. This supports a refined model of PPI network evolution in terms of protein domains under exponential and asymmetric duplication/divergence dynamics, with multidomain proteins underlying the combinatorial formation of protein complexes. Genome duplication then provides a powerful source of PPI network innovation by promoting local rearrangements of multidomain proteins on a genome wide scale. Yet, we show that the overall conservation and topology of PPI networks are robust to extensive domain shuffling of multidomain proteins as well as to finer details of protein interaction and evolution. Finally, large scale features of <it>direct </it>and <it>indirect </it>PPI networks of <it>S. cerevisiae </it>are well reproduced numerically with only two adjusted parameters of clear biological significance (<it>i.e</it>. network effective growth rate and average number of protein-binding domains per protein).</p> <p>Conclusion</p> <p>This study demonstrates the statistical consequences of genome duplication and domain shuffling on the conservation and topology of PPI networks over a broad evolutionary scale across eukaryote kingdoms. In particular, scale-free topologies of PPI networks, which are found to be robust to extensive shuffling of protein domains, appear to be a simple consequence of the conservation of protein-binding domains under asymmetric duplication/divergence dynamics in the course of evolution.</p

Bone sarcomas: ESMO–EURACAN–GENTURIS–ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up

Production costs have been covered by ESMO from central funds

Carbon cycle, vegetation and climate dynamics in the Holocene: Experiments with the CLIMBER-2 Model

Multiple proxy data reveal that the early to middle Holocene (ca. 8-6 kyr B. P.) was warmer than the preindustrial period in most regions of the Northern Hemisphere. This warming is presumably explained by the higher summer insolation in the Northern Hemisphere, owing to changes in the orbital parameters. Subsequent cooling in the late Holocene was accompanied by significant changes in vegetation cover and an increase in atmospheric CO2 concentration. The essential question is whether it is possible to explain these changes in a consistent way, accounting for the orbital parameters as the main external forcing for the climate system. We investigate this problem using the computationally efficient model of climate system, CLIMBER-2, which includes models for oceanic and terrestrial biogeochemistry. We found that changes in climate and vegetation cover in the northern subtropical and circumpolar regions can be attributed to the changes in the orbital forcing. Explanation of the atmospheric CO2 record requires an additional assumption of excessive CaCO3 sedimentation in the ocean. The modeled decrease in the carbonate ion concentration in the deep ocean is similar to that inferred from CaCO3 sediment data [Broecker et al., 1999]. For 8 kyr B. P., the model estimates the terrestrial carbon pool ca. 90 Pg higher than its preindustrial value. Simulated atmospheric delta(13)C declines during the course of the Holocene, similar to delta(13)C data from the Taylor Dome ice core [Indermuhle et al., 1999]. Amplitude of simulated changes in delta(13)C is smaller than in the data, while a difference between the model and the data is comparable with the range of data uncertainty