Monotonicity of Fitness Landscapes and Mutation Rate Control

A common view in evolutionary biology is that mutation rates are minimised. However, studies in combinatorial optimisation and search have shown a clear advantage of using variable mutation rates as a control parameter to optimise the performance of evolutionary algorithms. Much biological theory in this area is based on Ronald Fisher's work, who used Euclidean geometry to study the relation between mutation size and expected fitness of the offspring in infinite phenotypic spaces. Here we reconsider this theory based on the alternative geometry of discrete and finite spaces of DNA sequences. First, we consider the geometric case of fitness being isomorphic to distance from an optimum, and show how problems of optimal mutation rate control can be solved exactly or approximately depending on additional constraints of the problem. Then we consider the general case of fitness communicating only partial information about the distance. We define weak monotonicity of fitness landscapes and prove that this property holds in all landscapes that are continuous and open at the optimum. This theoretical result motivates our hypothesis that optimal mutation rate functions in such landscapes will increase when fitness decreases in some neighbourhood of an optimum, resembling the control functions derived in the geometric case. We test this hypothesis experimentally by analysing approximately optimal mutation rate control functions in 115 complete landscapes of binding scores between DNA sequences and transcription factors. Our findings support the hypothesis and find that the increase of mutation rate is more rapid in landscapes that are less monotonic (more rugged). We discuss the relevance of these findings to living organisms

Genomorama: genome visualization and analysis

<p>Abstract</p> <p>Background</p> <p>The ability to visualize genomic features and design experimental assays that can target specific regions of a genome is essential for modern biology. To assist in these tasks, we present Genomorama, a software program for interactively displaying multiple genomes and identifying potential DNA hybridization sites for assay design.</p> <p>Results</p> <p>Useful features of Genomorama include genome search by DNA hybridization (probe binding and PCR amplification), efficient multi-scale display and manipulation of multiple genomes, support for many genome file types and the ability to search for and retrieve data from the National Center for Biotechnology Information (NCBI) Entrez server.</p> <p>Conclusion</p> <p>Genomorama provides an efficient computational platform for visualizing and analyzing multiple genomes.</p

Microbiology of the phyllosphere: a playground for testing ecological concepts

Many concepts and theories in ecology are highly debated, because it is often difficult to design decisive tests with sufficient replicates. Examples include biodiversity theories, succession concepts, invasion theories, coexistence theories, and concepts of life history strategies. Microbiological tests of ecological concepts are rapidly accumulating, but have yet to tap into their full potential to complement traditional macroecological theories. Taking the example of microbial communities on leaf surfaces (i.e. the phyllosphere), we show that most explorations of ecological concepts in this field of microbiology focus on autecology and population ecology, while community ecology remains understudied. Notable exceptions are first tests of the island biogeography theory and of biodiversity theories. Here, the phyllosphere provides the unique opportunity to set up replicated experiments, potentially moving fields such as biogeography, macroecology, and landscape ecology beyond theoretical and observational evidence. Future approaches should take advantage of the great range of spatial scales offered by the leaf surface by iteratively linking laboratory experiments with spatial simulation models

M-GCAT: interactively and efficiently constructing large-scale multiple genome comparison frameworks in closely related species

BACKGROUND: Due to recent advances in whole genome shotgun sequencing and assembly technologies, the financial cost of decoding an organism's DNA has been drastically reduced, resulting in a recent explosion of genomic sequencing projects. This increase in related genomic data will allow for in depth studies of evolution in closely related species through multiple whole genome comparisons. RESULTS: To facilitate such comparisons, we present an interactive multiple genome comparison and alignment tool, M-GCAT, that can efficiently construct multiple genome comparison frameworks in closely related species. M-GCAT is able to compare and identify highly conserved regions in up to 20 closely related bacterial species in minutes on a standard computer, and as many as 90 (containing 75 cloned genomes from a set of 15 published enterobacterial genomes) in an hour. M-GCAT also incorporates a novel comparative genomics data visualization interface allowing the user to globally and locally examine and inspect the conserved regions and gene annotations. CONCLUSION: M-GCAT is an interactive comparative genomics tool well suited for quickly generating multiple genome comparisons frameworks and alignments among closely related species. M-GCAT is freely available for download for academic and non-commercial use at:

Chromatin Organization in Sperm May Be the Major Functional Consequence of Base Composition Variation in the Human Genome

Chromatin in sperm is different from that in other cells, with most of the genome packaged by protamines not nucleosomes. Nucleosomes are, however, retained at some genomic sites, where they have the potential to transmit paternal epigenetic information. It is not understood how this retention is specified. Here we show that base composition is the major determinant of nucleosome retention in human sperm, predicting retention very well in both genic and non-genic regions of the genome. The retention of nucleosomes at GC-rich sequences with high intrinsic nucleosome affinity accounts for the previously reported retention at transcription start sites and at genes that regulate development. It also means that nucleosomes are retained at the start sites of most housekeeping genes. We also report a striking link between the retention of nucleosomes in sperm and the establishment of DNA methylation-free regions in the early embryo. Taken together, this suggests that paternal nucleosome transmission may facilitate robust gene regulation in the early embryo. We propose that chromatin organization in the male germline, rather than in somatic cells, is the major functional consequence of fine-scale base composition variation in the human genome. The selective pressure driving base composition evolution in mammals could, therefore, be the need to transmit paternal epigenetic information to the zygote

A high-order FEM formulation for free and forced vibration analysis of a nonlocal nonlinear graded Timoshenko nanobeam based on the weak form quadrature element method

The purpose of this paper is to provide a high-order finite element method (FEM) formulation of nonlocal nonlinear nonlocal graded Timoshenko based on the weak form quadrature element method (WQEM). This formulation offers the advantages and flexibility of the FEM without its limiting low-order accuracy. The nanobeam theory accounts for the von Kármán geometric nonlinearity in addition to Eringen’s nonlocal constitutive models. For the sake of generality, a nonlinear foundation is included in the formulation. The proposed formulation generates high-order derivative terms that cannot be accounted for using regular first- or second-order interpolation functions. Hamilton’s principle is used to derive the variational statement which is discretized using WQEM. The results of a WQEM free vibration study are assessed using data obtained from a similar problem solved by the differential quadrature method (DQM). The study shows that WQEM can offer the same accuracy as DQM with a reduced computational cost. Currently the literature describes a small number of high-order numerical forced vibration problems, the majority of which are limited to DQM. To obtain forced vibration solutions using WQEM, the authors propose two different methods to obtain frequency response curves. The obtained results indicate that the frequency response curves generated by either method closely match their DQM counterparts obtained from the literature, and this is despite the low mesh density used for the WQEM systems

Biophilic architecture: a review of the rationale and outcomes

Contemporary cities have high stress levels, mental health issues, high crime levels and ill health, while the built environment shows increasing problems with urban heat island effects and air and water pollution. Emerging from these concerns is a new set of design principles and practices where nature needs to play a bigger part called “biophilic architecture”. This design approach asserts that humans have an innate connection with nature that can assist to make buildings and cities more effective human abodes. This paper examines the evidence for this innate human psychological and physiological link to nature and then assesses the emerging research supporting the multiple social, environmental and economic benefits of biophilic architecture