A framework for evolutionary systems biology

Background  

Many difficult problems in evolutionary genomics are related to mutations that have weak effects on fitness, as the consequences of mutations with large effects are often simple to predict. Current systems biology has accumulated much data on mutations with large effects and can predict the properties of knockout mutants in some systems. However experimental methods are too insensitive to observe small effects.     

The evolutionary dynamics of self-incompatibility systems

Self-incompatible flowering plants reject pollen that expresses the same mating specificity as the pistil (female reproductive tract). In most plant families, pollen and pistil mating specificities segregate as a single locus, the S locus. In at least two self-incompatibility systems, distinct pollen and pistil specificity genes are embedded in an extensive nonrecombining tract. To facilitate consideration of how new S locus specificities arise in systems with distinct pollen and pistil genes, we present a graphical model for the generation of hypotheses. It incorporates the evolutionary principle that nonreciprocal siring success (cross-pollinations between two plants produce seeds in only one direction) tends to favor the rejecting partner. This model suggests that selection within S-allele specificity classes could accelerate the rate of nonsynonymous (amino acid-changing) substitutions, with periodic selective sweeps removing segregating variation within classes. Accelerated substitution within specificity classes could also promote the origin of new S-allele specificities.     

The evolutionary history of quorum-sensing systems in bacteria

Communication among bacterial cells through quorum-sensing (QS) systems is used to regulate ecologically and medically important traits, including virulence to hosts. QS is widespread in bacteria; it has been demonstrated experimentally in diverse phylogenetic groups, and homologs to the implicated genes have been discovered in a large proportion of sequenced bacterial genomes. The widespread distribution of the underlying gene families (LuxI/R and LuxS) raises the questions of how often QS genes have been transferred among bacterial lineages and the extent to which genes in the same QS system exchange partners or coevolve. Phylogenetic analyses of the relevant gene families show that the genes annotated as LuxI/R inducer and receptor elements comprise two families with virtually no homology between them and with one family restricted to the gamma-Proteobacteria and the other more widely distributed. Within bacterial phyla, trees for the LuxS and the two LuxI/R families show broad agreement with the ribosomal RNA tree, suggesting that these systems have been continually present during the evolution of groups such as the Proteobacteria and the Firmicutes. However, lateral transfer can be inferred for some genes (e.g., from Firmicutes to some distantly related lineages for LuxS). In general, the inducer/receptor elements in the LuxI/R systems have evolved together with little exchange of partners, although loss or replacement of partners has occurred in several lineages of gamma-Proteobacteria, the group for which sampling is most intensive in current databases. For instance, in Pseudomonas aeruginosa, a transferred QS system has been incorporated into the pathway of a native one. Gene phylogenies for the main LuxI/R family in Pseudomonas species imply a complex history of lateral transfer, ancestral duplication, and gene loss within the genus.     

Amphioxus and tunicates as evolutionary model systems

One important question in evolutionary biology concerns the origin of vertebrates from invertebrates. The current consensus is that the proximate ancestor of vertebrates was an invertebrate chordate. Today, the invertebrate chordates comprise cephalochordates (amphioxus) and tunicates (each a subphylum in the phylum Chordata, which also includes the vertebrate subphylum). It was widely accepted that, within the chordates, tunicates represent the sister group of a clade of cephalochordates plus vertebrates. However, recent studies suggest that the evolutionary positions of tunicates and cephalochordates should be reversed, the implications of which are considered here. We also review the two major groups of invertebrate chordates and compare relative advantages (and disadvantages) of each as model systems for elucidating the origin of the vertebrates.     

Prediction of functional phosphorylation sites by incorporating evolutionary information

Protein phosphorylation is a ubiquitous protein post-translational modification, which plays an important role in cellular signaling systems underlying various physiological and pathological processes. Current in silico methods mainly focused on the prediction of phosphorylation sites, but rare methods considered whether a phosphorylation site is functional or not. Since functional phosphorylation sites are more valuable for further experimental research and a proportion of phosphorylation sites have no direct functional effects, the prediction of functional phosphorylation sites is quite necessary for this research area. Previous studies have shown that functional phosphorylation sites are more conserved than non-functional phosphorylation sites in evolution. Thus, in our method, we developed a web server by integrating existing phosphorylation site prediction methods, as well as both absolute and relative evolutionary conservation scores to predict the most likely functional phosphorylation sites. Using our method, we predicted the most likely functional sites of the human, rat and mouse proteomes and built a database for the predicted sites. By the analysis of overall prediction results, we demonstrated that protein phosphorylation plays an important role in all the enriched KEGG pathways. By the analysis of protein-specific prediction results, we demonstrated the usefulness of our method for individual protein studies. Our method would help to characterize the most likely functional phosphorylation sites for further studies in this research area.     

Mechanical sensitivity reveals evolutionary dynamics of mechanical systems

A classic question in evolutionary biology is how form–function relationships promote or limit diversification. Mechanical metrics, such as kinematic transmission (KT) in linkage systems, are useful tools for examining the evolution of form and function in a comparative context. The convergence of disparate systems on equivalent metric values (mechanical equivalence) has been highlighted as a source of potential morphological diversity under the assumption that morphology can evolve with minimal impact on function. However, this assumption does not account for mechanical sensitivity—the sensitivity of the metric to morphological changes in individual components of a structure. We examined the diversification of a four-bar linkage system in mantis shrimp (Stomatopoda), and found evidence for both mechanical equivalence and differential mechanical sensitivity. KT exhibited variable correlations with individual linkage components, highlighting the components that influence KT evolution, and the components that are free to evolve independently from KT and thereby contribute to the observed pattern of mechanical equivalence. Determining the mechanical sensitivity in a system leads to a deeper understanding of both functional convergence and morphological diversification. This study illustrates the importance of multi-level analyses in delineating the factors that limit and promote diversification in form–function systems.     

Plant self-incompatibility systems: a molecular evolutionary perspective

Incompatibility recognition systems preventing self-fertilization have evolved several times in independent lineages of Angiosperm plants, and three main model systems are well characterized at the molecular level [the gametophytic self-incompatibility (SI) systems of Solanaceae, Rosaceae and Anthirrhinum, the very different system of poppy, and the system in Brassicaceae with sporophytic control of pollen SI reactions]. In two of these systems, the genes encoding both components of pollen-pistil recognition are now known, showing clearly that these two proteins are distinct, that is, SI is a lock-and-key mechanism. Here, we review recent findings in the three well-studied systems in the light of these results and analyse their implications for understanding polymorphism and coevolution of the two SI genes, in the context of a tightly linked genome region.     

The evolutionary genetics of sexual systems in flowering plants.

Population genetic studies of the evolution of breeding systems in flowering plants are reviewed. The selective advantage of a gene's increasing the selfing rate is stressed. In the evolution of outbreeding mechanisms, some strong disadvantage to selfing must therefore be acting; it is suggested that this disadvantage is inbreeding depression. Populations with no absolute barrier to selfing, and with intermediate levels of self-fertilization, appear to be the most likely starting state for the evolution of outbreeding mechanisms. There is some evidence for inbreeding depression in such populations. The evolution of distyly and dioecy are considered in some detail. An explanation for the existence of supergenes controlling these systems is proposed. The breakdown of distyly and tristyly are also considered. The evolution of recombination rates in selfing and outcrossing species is examined briefly.     

Novel evolutionary relationship among four fish model systems

Knowledge of the correct phylogenetic relationships among animals is crucial for the valid interpretation of evolutionary trends in biology. Zebrafish, medaka, pufferfish and cichilds are fish models for development, genomics and comparative genetics studies, although their phylogenetic relationships have not been tested rigorously. The results of phylogenomic analysis based on 20 nuclear protein-coding genes confirmed the basal placement of zebrafish in the fish phylogeny but revealed an unexpected relationship among the other three species, contrary to traditionally held systematic views based on morphology. Our analyses show that medaka (Beloniformes) and cichlids (Perciformes) appear to be more closely related to each other than either of them is to pufferfish (Tetraodontiformes), suggesting that a re-interpretation of some findings in comparative biology might be required. In addition, phylogenomic analyses show that fish typically have more copies of nuclear genes than land vertebrates, supporting the fish-specific genome duplication hypothesis.     

An evolutionary perspective on the systems of adaptive immunity

We propose an evolutionary perspective to classify and characterize the diverse systems of adaptive immunity that have been discovered across all major domains of life. We put forward a new function‐based classification according to the way information is acquired by the immune systems: Darwinian immunity (currently known from, but not necessarily limited to, vertebrates) relies on the Darwinian process of clonal selection to ‘learn’ by cumulative trial‐and‐error feedback; Lamarckian immunity uses templated targeting (guided adaptation) to internalize heritable information on potential threats; finally, shotgun immunity operates through somatic mechanisms of variable targeting without feedback. We argue that the origin of Darwinian (but not Lamarckian or shotgun) immunity represents a radical innovation in the evolution of individuality and complexity, and propose to add it to the list of major evolutionary transitions. While transitions to higher‐level units entail the suppression of selection at lower levels, Darwinian immunity re‐opens cell‐level selection within the multicellular organism, under the control of mechanisms that direct, rather than suppress, cell‐level evolution for the benefit of the individual. From a conceptual point of view, the origin of Darwinian immunity can be regarded as the most radical transition in the history of life, in which evolution by natural selection has literally re‐invented itself. Furthermore, the combination of clonal selection and somatic receptor diversity enabled a transition from limited to practically unlimited capacity to store information about the antigenic environment. The origin of Darwinian immunity therefore comprises both a transition in individuality and the emergence of a new information system – the two hallmarks of major evolutionary transitions. Finally, we present an evolutionary scenario for the origin of Darwinian immunity in vertebrates. We propose a revival of the concept of the ‘Big Bang’ of vertebrate immunity, arguing that its origin involved a ‘difficult’ (i.e. low‐probability) evolutionary transition that might have occurred only once, in a common ancestor of all vertebrates. In contrast to the original concept, we argue that the limiting innovation was not the generation of somatic diversity, but the regulatory circuitry needed for the safe operation of amplifiable immune responses with somatically acquired targeting. Regulatory complexity increased abruptly by genomic duplications at the root of the vertebrate lineage, creating a rare opportunity to establish such circuitry. We discuss the selection forces that might have acted at the origin of the transition, and in the subsequent stepwise evolution leading to the modern immune systems of extant vertebrates.     

Ultrastructures and evolutionary modalities of flagellar and ciliary systems in protists

Summary— As both the ultrastructure and function of flagella and cilia have been for the main part remarkably conserved during Eukaryote, evolution, the question arises as to whether the variations observed at the organite ultrastural level, or at the level of the development of a flagellar or ciliary cellular system could be considered as systematic or phylogenetic criteria. With regard to the fundamental structure, the known variations concern: 1) the kinetosome (length, position and number of cartwheels, number of triplets, and respective lengths of the microtubules); 2) the transition zone (various structural types); 3) the axoneme (number of doublets, central tubules, arms); 4) the paraxonemal formations (presence, position, structure); 5) the membrane (intramembranous particles; intramembranous particles; addition of components, mastigonemes, scales); 6) the fibres associated with the kinetosomes. Some of these variations are characteristic of taxa, and are considered as phylogenetic markers. Regarding the variations in the number of ciliary or flagellar units per cell, the following can be distinguished: cells with only one kinetosome (Ks), carrying one flagellum; cells with 2 neighbouring Ks (primary Ks = 2A), only one Ks, or the 2 Ks, bearing a flagellum; cells with numerous flagella or cilia. We consider that this configuration can result from: a) addition of new Ks around the primary Ks, forming a primary group (PG): either by replication of the primary couple (2 × 2A in Karotomorpha; 2 × 2A in Phaeopolykrikos; 4(2 × 2A) in Polkrikos), or by addition of new Ks (N) without copy or replication of the primary Ks (2A + 2N in Polytomella; 2A +3N in Tetratrichomonas; 2A + 3N in Tetratrichomonas; 2A + 4N in Hexamastix; 2A + 6N in Pyramimonas octopus). b) amplification of each constituent of the primordial couple in opalinids. c) amplification of the primary group [yx(AA + 2N) with y = 2 in diplomonadida and y > 2 in calonymphidae. d) appearance in morphogenetic fields situated outside the primary group (but possibly related to it) of new Ks which then form secondary groups (SG) where they are arranged in polarized rows composed of juxtaposed cortical units (monokinetids). In this case, PG can be of type 2A+2N (1PG+1SG in lophomonadida; 1PG+2SG in some trichonymphina), or can lose some Ks, resulting in reduced PG (4 reduced PG+4GS in Staurojoenina, n reduced PG + nGS in spirotrichonymphina). The PG may even disappear; either partially leaving remnants in the form of MTOCs in Stephanopogon, or completely, as in cilliates where the general ciliature would represent on the SG. From the above, it is seen that: a) the pluriflagellar state in protists depends on only a small number of factors; b) the same factors are used in different groups; c) different states have been obtained within different groups. An analysis of the respective evolution of kinetosomes and centrioles is proposed.     

Engineering microbial systems to explore ecological and evolutionary dynamics

A major goal of biological research is to provide a mechanistic understanding of diverse biological processes. To this end, synthetic biology offers a powerful approach, whereby biological questions can be addressed in a well-defined framework. By constructing simple gene circuits, such studies have generated new insights into the design principles of gene regulatory networks. Recently, this strategy has been applied to analyze ecological and evolutionary questions, where population-level interactions are critical. Here, we highlight recent development of such systems and discuss how they were used to address problems in ecology and evolutionary biology. As illustrated by these examples, synthetic ecosystems provide a unique platform to study ecological and evolutionary phenomena that are challenging to study in their natural contexts.     

Prediction of distant residue contacts with the use of evolutionary information

In this work we present a novel correlated mutations analysis (CMA) method that is significantly more accurate than previously reported CMA methods. Calculation of correlation coefficients is based on physicochemical properties of residues (predictors) and not on substitution matrices. This results in reliable prediction of pairs of residues that are distant in protein sequence but proximal in its three dimensional tertiary structure. Multiple sequence alignments (MSA) containing a sequence of known structure for 127 families from PFAM database have been selected so that all major protein architectures described in CATH classification database are represented. Protein sequences in the selected families were filtered so that only those evolutionarily close to the target protein remain in the MSA. The average accuracy obtained for the alpha beta class of proteins was 26.8% of predicted proximal pairs with average improvement over random accuracy (IOR) of 6.41. Average accuracy is 20.6% for the mainly beta class and 14.4% for the mainly alpha class. The optimum correlation coefficient cutoff (cc cutoff) was found to be around 0.65. The first predictor, which correlates to hydrophobicity, provides the most reliable results. The other two predictors give good predictions which can be used in conjunction to those of the first one. When stricter cc cutoff is chosen, the average accuracy increases significantly (38.76% for alpha beta class), but the trade off is a smaller number of predictions. The use of solvent accessible area estimations for filtering false positives out of the predictions is promising.     

Fish species diversity in southern African estuarine systems: an evolutionary perspective

Synopsis The ichthyofauna of southern African estuaries consists primarily of juvenile marine species that use these habitats as nursery areas. The abundance and biomass of fishes in estuarine systems are typically high but species diversity is generally low, with only a few taxa dominating the community. This relatively low species diversity is attributed to the fact that estuaries in the region are unpredictable environments which lack any degree of permanence and are dominated by mobile marine eurytopes. Although stenotopes, represented mainly by small resident species from the families Gobiidae, Clinidae and Syngnathidae, are present in southern African estuaries, little speciation appears to have occurred. A possible reason for this lack of speciation, apart from the seasonal and annual variability of the abiotic environment, is that the lifetime of individual systems is usually limited to a few thousand years. In addition, fishes utilising southern African estuaries need to remain flexible (eurytopic) in their responses to an external environment which is unlikely to become more stable in the future. Thus the lack of permanence and fluctuating nature of southern African estuaries on both a spatial and temporal scale, together with the dominance of eurytopes in these systems, does not favour the evolution of new species. A preliminary examination of the available literature indicates that a detailed review of estuarine ichthyofaunal communities on a global basis will probably mirror the trends outlined above, and reveal a domination of these dynamic ecosystems by eurytopic taxa with low speciation potential.