Deleterious Passengers in Adapting Populations

Most new mutations are deleterious and are eventually eliminated by natural selection. But in an adapting population, the rapid amplification of beneficial mutations can hinder the removal of deleterious variants in nearby regions of the genome, altering the patterns of sequence evolution. Here, we analyze the interactions between beneficial “driver” mutations and linked deleterious “passengers” during the course of adaptation. We derive analytical expressions for the substitution rate of a deleterious mutation as a function of its fitness cost, as well as the reduction in the beneficial substitution rate due to the genetic load of the passengers. We find that the fate of each deleterious mutation varies dramatically with the rate and spectrum of beneficial mutations and the deleterious substitution rate depends nonmonotonically on the population size and the rate of adaptation. By quantifying this dependence, our results allow us to estimate which deleterious mutations will be likely to fix and how many of these mutations must arise before the progress of adaptation is significantly reduced.     

Adapting antibodies for clinical use.

Techniques for antibody engineering are now overcoming the problems that have prevented monoclonal antibodies being used routinely in clinical practice. With chemical and genetic manipulation antibodies can be linked to bacterial toxins, enzymes, radionuclides, or cytotoxic drugs, allowing targeting of treatment. Antigen binding sites from antibodies raised in mice can be jointed with human IgG to reduce immunogenicity. In vitro gene amplification and genetic engineering of bacteriophage have produced large antibody gene libraries and facilitated large scale production of human monoclonal antibodies with high specificity. The trickle of monoclonal antibodies into clinical practice may soon become a flood.     

Action Spectra for Phycobiliprotein Synthesis in a Chromatically Adapting Cyanophyte, Fremyella diplosiphon

The action spectra for phycocyanin production by the cyanophyte Fremyella diplosiphon shows maxima at 463 and 641 nm. The action spectrum for phycoerythrin production includes maxima at 387 and 550 nm. The maxima are based on a relative response rate well within the linear ascending portion of the dose response curves; the positions of the maxima are independent of the relative response rates chosen for reference over a 3-fold range although the comparative effectiveness of light at pairs of wavelengths varies with the standard used for comparison. These action spectra differ from those reported previously for Tolypothrix tenuis by Fujita and Hattori (Plant Cell Physiol. 3: 209-220) and by Diakoff and Scheibe (Plant Physiol. 51: 382-385) in that blue light strongly promotes phycobiliprotein synthesis in F. diphosiphon but has been reported to have little or no effect on T. tenuis.     

Adapting arrays and lab-on-a-chip technology for proteomics

The impact of proteomics as a discovery engine in life science and in drug discovery has increased tremendously over the last seven years. At the same time, proteomics has expanded from the initial trust as a two-dimensional gel based approach to cover more functional and structural properties of proteins. The development of lab-on-a-chip and protein arrays for proteomics will have to evolve with the changes in proteomics to stay relevant. Here, we review the changes in the field of proteomics and their impact on the development in protein arrays and lab-on-a-chip.     

Adapting to environmental changes using specialized paralogs

When a bacterial species survives under changing environmental circumstances (e.g. salinity or temperature), its proteins might not function in all physicochemical conditions. We propose that prokaryotes cope with this problem by having two or more copies of the genes affected by environmental fluctuations, each one performing the same function under different conditions (i.e. ecoparalog). We identify potential examples in the bacterium Salinibacter ruber and in other species that experience wide environmental variations.     

Adapting protein sequences for optimized therapeutic efficacy

Therapeutic proteins alleviate disease pathology by supplementing missing or defective native proteins, sequestering superfluous proteins, or by acting through designed non-natural mechanisms. Although therapeutic proteins often have the same amino acid sequence as their native counterpart, their maturation paths from expression to the site of physiological activity are inherently different, and optimizing protein sequences for properties that 100s of millions of years of evolution did not need to address presents an opportunity to develop better biological treatments. Because therapeutic proteins are inherently non-natural entities, optimization for their desired function should be considered analogous to that of small molecule drug candidates, which are optimized through expansive combinatorial variation by the medicinal chemist. Here, we review recent successes and challenges of protein engineering for optimized therapeutic efficacy.     

Adapting genetic regulatory models by genetic programming

In this paper, we focus on the task of adapting genetic regulatory models based on gene expression data from microarrays. Our approach aims at automatic revision of qualitative regulatory models to improve their fit to expression data. We describe a type of regulatory model designed for this purpose, a method for predicting the quality of such models, and a method for adapting the models by means of genetic programming. We also report experimental results highlighting the ability of the methods to infer models on a number of artificial data sets. In closing, we contrast our results with those of alternative methods, after which we give some suggestions for future work.     

Adapting systematic conservation planning for climate change

With the high rate of ecosystem change, effective systematic conservation planning must account for ongoing and imminent threats to biodiversity to ensure its persistence. Accordingly, guidance on appropriate conservation actions in the face of climate change has been accumulating. We review this guidance and bring together the key recommendations needed to successfully account for climate change impacts, relevant to the scale at which natural resource management is carried out. We discuss how the traditional conservation tools of protection and restoration need to be adjusted to be effective in the face of climate change. We highlight the conservation innovations such as moveable and temporary reserves, and Targeted Gene Flow. We build on recent work to provide critical advice for considering climate change in conservation planning. In particular, we discuss how stating explicit objectives related to climate change adaptation, quantifying uncertainty, and exploring trade-offs will better place conservation plans to meet objectives for multiple goals such as protection of species, ecosystems, geophysical diversity and ecological processes.