Under-dominance constrains the evolution of negative autoregulation in diploids

Regulatory networks have evolved to allow gene expression to rapidly track changes in the environment as well as to buffer perturbations and maintain cellular homeostasis in the absence of change. Theoretical work and empirical investigation in Escherichia coli have shown that negative autoregulation confers both rapid response times and reduced intrinsic noise, which is reflected in the fact that almost half of Escherichia coli transcription factors are negatively autoregulated. However, negative autoregulation is rare amongst the transcription factors of Saccharomyces cerevisiae. This difference is surprising because E. coli and S. cerevisiae otherwise have similar profiles of network motifs. In this study we investigate regulatory interactions amongst the transcription factors of Drosophila melanogaster and humans, and show that they have a similar dearth of negative autoregulation to that seen in S. cerevisiae. We then present a model demonstrating that this stiking difference in the noise reduction strategies used amongst species can be explained by constraints on the evolution of negative autoregulation in diploids. We show that regulatory interactions between pairs of homologous genes within the same cell can lead to under-dominance - mutations which result in stronger autoregulation, and decrease noise in homozygotes, paradoxically can cause increased noise in heterozygotes. This severely limits a diploid's ability to evolve negative autoregulation as a noise reduction mechanism. Our work offers a simple and general explanation for a previously unexplained difference between the regulatory architectures of E. coli and yeast, Drosophila and humans. It also demonstrates that the effects of diploidy in gene networks can have counter-intuitive consequences that may profoundly influence the course of evolution

Imaging in Osteoporosis

This is the author accepted manuscript. The final version is available from Pavilion Publishing via the link in this record.Osteoporosis is a prevalent metabolic bone disease in the western world, resulting in low trauma fractures and increased morbidity and mortality rates among sufferers. The article describes the common imaging required in the diagnosis and management of osteoporosis. It is important to include imaging within the patient pathway where vertebral fractures are suspected and to use additional imaging modalities such as MRI to aid differential diagnosis where the cause of the fracture is unclear. Radiographers and radiologists reporting imaging examinations may be the first clinicians to suspect the presence of osteoporosis and have a role in helping to ensure that these patients do not get missed so that appropriate treatment can be started. Ideally there should be locally-agreed pathways whereby such patients are automatically referred to the fracture liaison service, regardless of the original requester of the imaging investigation

Differential regulation drives plasticity in sex determination gene networks

Background: Sex determination networks evolve rapidly and have been studied intensely across many species, particularly in insects, thus presenting good models to study the evolutionary plasticity of gene networks.Results: We study the evolution of an unlinked gene capable of regulating an existing diploid sex determination system. Differential gene expression determines phenotypic sex and fitness, dramatically reducing the number of assumptions of previous models. It allows us to make a quantitative evaluation of the full range of evolutionary outcomes of the system and an assessment of the likely contribution of sexual conflict to change in sex determination systems. Our results show under what conditions network mutations causing differential regulation can lead to the reshaping of sex determination networks.Conclusion: The analysis demonstrates the complex relationship between mutation and outcome: the same mutation can produce many different evolved populations, while the same evolved population can be produced by many different mutations. Existing network structure alters the constraints and frequency of evolutionary changes, which include the recruitment of new regulators, changes in heterogamety, protected polymorphisms, and transitions to a new locus that controls sex determination

The population genetics of cooperative gene regulation.

Changes in gene regulatory networks drive the evolution of phenotypic diversity both within and between species. Rewiring of transcriptional networks is achieved either by changes to transcription factor binding sites or by changes to the physical interactions among transcription factor proteins. It has been suggested that the evolution of cooperative binding among factors can facilitate the adaptive rewiring of a regulatory network

Dynamics of mitochondrial inheritance in the evolution of binary mating types and two sexes

The uniparental inheritance (UPI) of mitochondria is thought to explain the evolution of two mating types or even true sexes with anisogametes. However, the exact role of UPI is not clearly understood. Here, we develop a new model, which considers the spread of UPI mutants within a biparental inheritance (BPI) population. Our model explicitly considers mitochondrial mutation and selection in parallel with the spread of UPI mutants and self-incompatible mating types. In line with earlier work, we find that UPI improves fitness under mitochondrial mutation accumulation, selfish conflict and mitonuclear coadaptation. However, we find that as UPI increases in the population its relative fitness advantage diminishes in a frequency-dependent manner. The fitness benefits of UPI 'leak' into the biparentally reproducing part of the population through successive matings, limiting the spread of UPI. Critically, while this process favours some degree of UPI, it neither leads to the establishment of linked mating types nor the collapse of multiple mating types to two. Only when two mating types exist beforehand can associated UPI mutants spread to fixation under the pressure of high mitochondrial mutation rate, large mitochondrial population size and selfish mutants. Variation in these parameters could account for the range of UPI actually observed in nature, from strict UPI in some Chlamydomonas species to BPI in yeast. We conclude that UPI of mitochondria alone is unlikely to have driven the evolution of two mating types in unicellular eukaryotes

Can we manage coastal ecosystems to sequester more blue carbon?

© The Ecological Society of America To promote the sequestration of blue carbon, resource managers rely on best-management practices that have historically included protecting and restoring vegetated coastal habitats (seagrasses, tidal marshes, and mangroves), but are now beginning to incorporate catchment-level approaches. Drawing upon knowledge from a broad range of environmental variables that influence blue carbon sequestration, including warming, carbon dioxide levels, water depth, nutrients, runoff, bioturbation, physical disturbances, and tidal exchange, we discuss three potential management strategies that hold promise for optimizing coastal blue carbon sequestration: (1) reducing anthropogenic nutrient inputs, (2) reinstating top-down control of bioturbator populations, and (3) restoring hydrology. By means of case studies, we explore how these three strategies can minimize blue carbon losses and maximize gains. A key research priority is to more accurately quantify the impacts of these strategies on atmospheric greenhouse-gas emissions in different settings at landscape scales