Multiobjective evolutionary optimization in antibody purification process design

To contribute towards designing more cost-efficient, robust and flexible downstream processes for the manufacture of monoclonal antibodies (mAbs), a framework consisting of an evolutionary multiobjective optimization algorithm (EMOA) linked to a biomanufacturing process economics model is presented. The EMOA is tuned to discover sequences of chromatographic purification steps and column sizing strategies that provide the best trade-off with respect to multiple objectives including cost of goods per gram (COG/g), robustness in COG/g, and impurity removal capabilities. Additional complexities accounted for by the framework include uncertainties and constraints. The framework is validated on industrially relevant case studies varying in upstream and downstream processing train ratios, annual demands, and impurity loads. Results obtained by the framework are presented using a range of visualization tools, and indicate that the performance impact of uncertainty is a function of both the level of uncertainty and the objective being optimized, and that uncertainty can cause otherwise optimal processes to become suboptimal. The optimal purification processes discovered outperform the industrial standard with, e.g. savings in COG/g of up to 10%. Guidelines are provided for choosing an optimal purification process as a function of the objectives being optimized and impurity levels present.     

Pathogen‐induced maternal effects result in enhanced immune responsiveness across generations

Parental investment theory postulates that adults can accurately perceive cues from their surroundings, anticipate the needs of future offspring based on those cues, and selectively allocate nongenetic resources to their progeny. Such context‐dependent parental contributions can result in phenotypically variable offspring. Consistent with these predictions, we show that bacterially exposed Manduca sexta mothers oviposited significantly more variable embryos (as measured by mass, volume, hatching time, and hatching success) relative to naïve and control mothers. By using an in vivo “clearance of infection” assay, we also show that challenged larvae born to heat‐killed‐ or live‐Serratia‐injected mothers, supported lower microbial loads and cleared the infection faster than progeny of control mothers. Our data support the notion that mothers can anticipate the future pathogenic risks and immunological needs of their unborn offspring, providing progeny with enhanced immune protection likely through transgenerational immune priming. Although the inclusion of live Serratia into oocytes does not appear to be the mechanism by which mothers confer protection to their young, other mechanisms, including epigenetic modifications in the progeny due to maternal pathogenic stress, may be at play. The adaptive nature of maternal effects in the face of pathogenic stress provides insights into parental investment, resource allocation, and life‐history theories and highlights the significant role that pathogen‐induced maternal effects play as generators and modulators of evolutionary change.     

Cooperation: integrating evolutionary and ecological perspectives

Putting a competitive squeeze on a cooperative group has long been considered to encourage cheats. Now we learn that competition, by driving diversification among cooperators, can create groups that are both more productive and more resistant to defection.     

Chromothripsis,a credible chromosomal mechanism in evolutionary process

Chromosoma - The recent discovery of a new class of massive chromosomal rearrangements, occurring during one unique cellular event and baptized “chromothripsis,” deeply modifies our...     

Progressive improvement in the transfer of maternal antibody across the order Primates

Antibody levels were determined in adults and newborn offspring of five primate species. This cross-species comparison of intant IgG levels indicated that prosimians and New World monkeys transfer lower levels of maternal antibody via placental transmission than do Old World monkeys, apes, and humans. The evolutionary trend toward an increased reliance on prenatal antibody transfer in the higher primates appears to be most pronounced in the human infant, because our placenta has evolved an active transport process that elevates IgG in the full-term fetus over maternal levels. Higher IgG levels in the young infant ensure a more prolonged and successful period of passive immunity against pathogens previously encountered by the mother. © 1994 Wiley-Liss, Inc.     

Understanding the function of bacterial and eukaryotic thiolases II by integrating evolutionary and functional approaches

Acetoacetyl-CoA thiolase (EC 2.3.1.9), commonly named thiolase II, condenses two molecules of acetyl-CoA to give acetoacetyl-CoA and CoA. This enzyme acts in anabolic processes as the first step in the biosynthesis of isoprenoids and polyhydroxybutyrate in eukaryotes and bacteria, respectively. We have recently reported the evolutionary and functional equivalence of these enzymes, suggesting that thiolase II could be the rate limiting enzyme in these pathways and presented evidence indicating that this enzyme modulates the availability of reducing equivalents during abiotic stress adaptation in bacteria and plants. However, these results are not sufficient to clarify why thiolase II was evolutionary selected as a critical enzyme in the production of antioxidant compounds. Regarding this intriguing topic, we propose that thiolase II could sense changes in the acetyl-CoA/CoA ratio induced by the inhibition of the tricarboxylic acid cycle under abiotic stress. Thus, the high level of evolutionary and functional constraint of thiolase II may be due to the connection of this enzyme with an ancient and conserved metabolic route.     

Introduction: integrating genetic and cultural evolutionary approaches to language

The papers in this special issue of Human Biology address recent research in the field of language evolution, both the genetic evolution of the language faculty and the cultural evolution of specific languages. While both of these areas have received increasing interest in recent years, there is also a need to integrate these somewhat separate efforts and explore the relevant gene-culture coevolutionary interactions. Here we summarize the individual contributions, set them in the context of the wider literature, and identify outstanding future research questions. The first set of papers concerns the comparative study of nonhuman communication in primates and birds from both a behavioral and neurobiological perspective, revealing evidence for several common language-related traits in various nonhuman species and providing clues as to the evolutionary origin and function of the human language faculty. The second set of papers discusses the consequences of viewing language as a culturally evolving system in its own right, including claims that this removes the need for strong genetic biases for language acquisition, and that phylogenetic evolutionary methods can be used to reconstruct language histories. We conclude by highlighting outstanding areas for future research, including identifying the precise selection pressures that gave rise to the language faculty in ancestral hominin species, and determining the strength, domain specificity, and origin of the cultural transmission biases that shape languages as they pass along successive generations of language learners.     

Grandparental effects in marine sticklebacks: transgenerational plasticity across multiple generations

Nongenetic inheritance mechanisms such as transgenerational plasticity (TGP) can buffer populations against rapid environmental change such as ocean warming. Yet, little is known about how long these effects persist and whether they are cumulative over generations. Here, we tested for adaptive TGP in response to simulated ocean warming across parental and grandparental generations of marine sticklebacks. Grandparents were acclimated for two months during reproductive conditioning, whereas parents experienced developmental acclimation, allowing us to compare the fitness consequences of short‐term vs. prolonged exposure to elevated temperature across multiple generations. We found that reproductive output of F1 adults was primarily determined by maternal developmental temperature, but carry‐over effects from grandparental acclimation environments resulted in cumulative negative effects of elevated temperature on hatching success. In very early stages of growth, F2 offspring reached larger sizes in their respective paternal and grandparental environment down the paternal line, suggesting that other factors than just the paternal genome may be transferred between generations. In later growth stages, maternal and maternal granddam environments strongly influenced offspring body size, but in opposing directions, indicating that the mechanism(s) underlying the transfer of environmental information may have differed between acute and developmental acclimation experienced by the two generations. Taken together, our results suggest that the fitness consequences of parental and grandparental TGP are highly context dependent, but will play an important role in mediating some of the impacts of rapid climate change in this system.     

Deciphering function and mechanism of calcium-binding proteins from their evolutionary imprints

Calcium-binding proteins regulate ion metabolism and vital signalling pathways in all living organisms. Our aim is to rationalize the molecular basis of their function by studying their evolution using computational biology techniques. Phylogenetic analysis is of primary importance for classifying cognate orthologs; profile hidden Markov models (HMM) of individual subfamilies discern functionally relevant sites by conservation probability analysis; and 3-dimensional structures display the integral protein in context. The major classifications of calcium-binding proteins, viz. EF-hand, C2 and ANX, exhibit structural diversity in their HMM fingerprints at the subfamily level, with functional consequences for protein conformation, exposure of receptor interaction sites and/or binding to membrane phospholipids. Calmodulin, S100 and annexin families were characterized in Petromyzon marinus (sea lamprey) to document genome duplication and gene creation events during the key evolutionary transition to primitive vertebrates. Novel annexins from diverse organisms revealed calcium-binding domains with accessory structural features that define their unique molecular fingerprints, protein interactivity and functional specificity. These include the first single-domain, bacterial annexin in Cytophaga hutchinsonii, the 21 tetrad annexins from the unicellular protist Giardia intestinalis, an ancestor to land plant annexins from the green alga Ostreococcus lucimarinus, invertebrate octad annexins and a critical polymorphism in human ANXA7. Receptor docking models supported the hypothesis of a potential interaction between annexin and C2 domains as a propitious mechanism for ensuring membrane translocation during signal transduction.     

Social plasticity in fish: integrating mechanisms and function

Social plasticity is a ubiquitous feature of animal behaviour. Animals must adjust the expression of their social behaviour to the nuances of daily social life and to the transitions between life‐history stages, and the ability to do so affects their Darwinian fitness. Here, an integrative framework is proposed for understanding the proximate mechanisms and ultimate consequences of social plasticity. According to this framework, social plasticity is achieved by rewiring or by biochemically switching nodes of the neural network underlying social behaviour in response to perceived social information. Therefore, at the molecular level, it depends on the social regulation of gene expression, so that different brain genomic and epigenetic states correspond to different behavioural responses and the switches between states are orchestrated by signalling pathways that interface the social environment and the genotype. At the evolutionary scale, social plasticity can be seen as an adaptive trait that can be under positive selection when changes in the environment outpace the rate of genetic evolutionary change. In cases when social plasticity is too costly or incomplete, behavioural consistency can emerge by directional selection that recruits gene modules corresponding to favoured behavioural states in that environment. As a result of this integrative approach, how knowledge of the proximate mechanisms underlying social plasticity is crucial to understanding its costs, limits and evolutionary consequences is shown, thereby highlighting the fact that proximate mechanisms contribute to the dynamics of selection. The role of teleosts as a premier model to study social plasticity is also highlighted, given the diversity and plasticity that this group exhibits in terms of social behaviour. Finally, the proposed integrative framework to social plasticity also illustrates how reciprocal causation analysis of biological phenomena (i.e. considering the interaction between proximate factors and evolutionary explanations) can be a more useful approach than the traditional proximate–ultimate dichotomy, according to which evolutionary processes can be understood without knowledge on proximate causes, thereby black‐boxing developmental and physiological mechanisms.     

Predicting plant responses to mycorrhizae: integrating evolutionary history and plant traits

We assessed whether (1) arbuscular mycorrhizal colonization of roots (RC) and/or plant responses to arbuscular mycorrhizae (MR) vary with plant phylogeny and (2) MR and RC can be more accurately predicted with a phylogenetic predictor relative to a null model and models with plant trait and taxonomic predictors. In a previous study, MR and RC of 95 grassland species were measured. We constructed a phylogeny for these species and found it explained variation in MR and RC. Next, we used multiple regressions to identify the models that most accurately predicted plant MR. Models including either phylogenetic or phenotypic and taxonomic information similarly improved our ability to predict MR relative to a null model. Our study illustrates the complex evolutionary associations among species and constraints of using phylogenetic information, relative to plant traits, to predict how a plant species will interact with AMF.     

The origin and maintenance of montane diversity: integrating evolutionary and ecological processes

Determining how ecological and evolutionary processes produce spatial variation in local species richness remains an unresolved challenge. Using mountains as a model system, we outline an integrative research approach to evaluate the influence of ecological and evolutionary mechanisms on the generation and maintenance of patterns of species richness along and among elevational gradients. Biodiversity scientists interested in patterns of species richness typically start by documenting patterns of species richness at regional and local scales, and based on their knowledge of the taxon, and the environmental and historical characteristics of a mountain region, they then ask whether diversity–environment relationships, if they exist, are explained mostly by ecological or evolutionary hypotheses. The final step, and perhaps most challenging one, is to tease apart the relative influence of ecological and evolutionary mechanisms. We propose that elucidating the relative influence of ecological and evolutionary mechanisms can be achieved by taking advantage of the replicated settings afforded by mountains, combined with targeted experiments along elevational gradients. This approach will not only identify potential mechanisms that drive patterns of species richness, but also allow scientists to generate more robust hypotheses about which factors generate and maintain local diversity.     

Elder knowledge and sustainable livelihoods in post-Soviet Russia: finding dialogue across the generations

Russia's indigenous peoples have been struggling with economic, environmental, and socio-cultural dislocation since the fall of the Soviet Union in 1991. In northern rural areas, the end of the Soviet Union most often meant the end of agro-industrial state farm operations that employed and fed surrounding rural populations. Most communities adapted to this loss by reinstating some form of pre-Soviet household-level food production based on hunting, fishing, and/or herding. However, mass media, globalization, and modernity challenge the intergenerational knowledge exchange that grounds subsistence practices. Parts of the circumpolar north have been relatively successful in valuing and integrating elder knowledge within their communities. This has not been the case in Russia. This article presents results of an elder knowledge project in northeast Siberia, Russia that shows how rural communities can both document and use elder knowledge to bolster local definitions of sustainability and, at the same time, initiate new modes of communication between village youth and elders.     

Electron microscopy in cell biology: integrating structure and function

Electron microscopy (EM) is at the highest-resolution limit of a spectrum of complementary morphological techniques. When combined with molecular detection methods, EM is the only technique with sufficient resolution to localize proteins to small membrane subdomains in the context of the cell. Recent procedural and technical developments have increasingly improved the power of EM as a cell-biological tool.     

Genome methylation patterns across castes and generations in a parasitoid wasp

Environmental influences shape phenotypes within and across generations, often through DNA methylations that modify gene expression. Methylations were proposed to mediate caste and task allocation in some eusocial insects, but how an insect's environment affects DNA methylation in its offspring is yet unknown. We characterized parental effects on methylation profiles in the polyembryonic parasitoid wasp Copidosoma koehleri, as well as methylation patterns associated with its simple caste system. We used methylation‐sensitive amplified fragment length polymorphism (MS‐AFLP) to compare methylation patterns, among (1) reproductive and soldier larvae; and (2) offspring (larvae, pupae, and adults) of wasps that were reared at either high or low larval density and mated in the four possible combinations. Methylation frequencies were similar across castes, but the profiles of methylated fragments differed significantly. Parental rearing density did not affect methylation frequencies in the offspring at any developmental stage. Principal coordinate analysis indicated no significant differences in methylation profiles among the four crossbreeding groups and the three developmental stages. Nevertheless, a clustering analysis, performed on a subset of the fragments, revealed similar methylation patterns in larvae, pupae, and adults in two of the four parental crosses. Nine fragments were methylated at two cytosine sites in all larvae, and five others were methylated at two sites in all adults. Thus, DNA methylations correlate with within‐generation phenotypic plasticity due to caste. However, their association with developmental stage and with transgenerational epigenetic effects is not clearly supported.     

DoBo: Protein domain boundary prediction by integrating evolutionary signals and machine learning

Background  

Accurate identification of protein domain boundaries is useful for protein structure determination and prediction. However, predicting protein domain boundaries from a sequence is still very challenging and largely unsolved.     

Natural hybridization in primates: one evolutionary mechanism

The role and importance of natural hybridization in the evolutionary histories of animal taxa is still debated. This results largely from a history of zoological investigations that assumed, rather than documented, a limited evolutionary role for this process. However, it is now becoming apparent that, just as for plants, the creative effects of reticulate evolution are widespread in animal taxa as well. This conclusion is supported by the documentation of numerous instances of the formation of new taxa and the genetic enrichment through introgressive hybridization. In the present review, we use primates as a paradigm for how natural hybridization can affect the evolution of species complexes and remains a footprint on genomes. Findings for a number of groups, including basal (e.g. lemurs) and derived (e.g. Old World apes) lineages, demonstrate that introgression and hybrid speciation have caused a reticulate pattern that is still detectable in the, often mosaic, genomes of primates. For example, results from genetic analyses of our own species demonstrate the process of past introgressive hybridization with the progenitors of our sister taxa (i.e. chimpanzees and gorillas) and most likely also our extinct, close relatives in the hominid lineage.