The limits of protein sequence comparison?

Modern sequence alignment algorithms are used routinely to identify homologous proteins, proteins that share a common ancestor. Homologous proteins always share similar structures and often have similar functions. Over the past 20 years, sequence comparison has become both more sensitive, largely because of profile-based methods, and more reliable, because of more accurate statistical estimates. As sequence and structure databases become larger, and comparison methods become more powerful, reliable statistical estimates will become even more important for distinguishing similarities that are due to homology from those that are due to analogy (convergence). The newest sequence alignment methods are more sensitive than older methods, but more accurate statistical estimates are needed for their full power to be realized.     

What determines the rate of sequence evolution?

High rates of amino-acid sequence evolution have sometimes been considered to be diagnostic for genes undergoing adaptive change. However, two recent studies have shown that rapid evolution of amino-acid sequence can also be congruent with neutrality.     

What's in a likelihood? Simple models of protein evolution and the contribution of structurally viable reconstructions to the likelihood

Most phylogenetic models of protein evolution assume that sites are independent and identically distributed. Interactions between sites are ignored, and the likelihood can be conveniently calculated as the product of the individual site likelihoods. The calculation considers all possible transition paths (also called substitution histories or mappings) that are consistent with the observed states at the terminals, and the probability density of any particular reconstruction depends on the substitution model. The likelihood is the integral of the probability density of each substitution history taken over all possible histories that are consistent with the observed data. We investigated the extent to which transition paths that are incompatible with a protein's three-dimensional structure contribute to the likelihood. Several empirical amino acid models were tested for sequence pairs of different degrees of divergence. When simulating substitutional histories starting from a real sequence, the structural integrity of the simulated sequences quickly disintegrated. This result indicates that simple models are clearly unable to capture the constraints on sequence evolution. However, when we sampled transition paths between real sequences from the posterior probability distribution according to these same models, we found that the sampled histories were largely consistent with the tertiary structure. This suggests that simple empirical substitution models may be adequate for interpolating changes between observed sequences during phylogenetic inference despite the fact that the models cannot predict the effects of structural constraints from first principles. This study is significant because it provides a quantitative assessment of the biological realism of substitution models from the perspective of protein structure, and it provides insight on the prospects for improving models of protein sequence evolution.     

Structural studies of the TGF-βs and their receptors - insights into evolution of the TGF-β superfamily

TGF-βs are small secreted signaling proteins that function as vital regulators of cellular growth and differentiation. They signal through a single pair of receptors, known as TβR-I and TβR-II, and are among the most recently evolved members of the signaling superfamily to which they belong. This review provides an overview of the TGF-β, BMP, and activin receptor complexes that have been determined over the past several years. These structures underscore the shared ancestry of the TGF-βs with the BMPs and activins, but also provide insight as to how the TGF-βs diverged from the BMPs and activins to bind and assemble their receptors in a distinct manner. These distinctive modes of receptor binding engender the TGF-βs with high specificity for their receptors and allow them to fulfill their essential functions in vivo without interference from the many other proteins of the superfamily.     

A model for the evolution of crèching behaviour in gulls

A crèche is an aggregation of chicks outside nesting territories, within chicks continue to be fed only by their own parents. Several adaptive functions of crèching have been proposed, the most frequent being a reduction in predator pressure. Using an evolutionary stable strategy approach based on the computation of individuals' fecundity, we examined which regime of aerial and terrestrial predation is likely to favour the evolution and stability of the crèching strategy (CS) in gulls. Our results confirm the hypothesis that habitat instability associated with high levels of terrestrial predation favours the evolution and maintenance of crèching behaviour. Moreover, our results suggest that a low aggressiveness against predators may be a pre-adaptation to a CS. In contrast, the high synchronisation often observed in crèching species does not favour the evolution of a crèching behaviour and is thus probably under selection pressures different from those modelled here.     

The ‘division of labour’ model of eye evolution

The ‘division of labour’ model of eye evolution is elaborated here. We propose that the evolution of complex, multicellular animal eyes started from a single, multi-functional cell type that existed in metazoan ancestors. This ancient cell type had at least three functions: light detection via a photoreceptive organelle, light shading by means of pigment granules and steering through locomotor cilia. Located around the circumference of swimming ciliated zooplankton larvae, these ancient cells were able to mediate phototaxis in the absence of a nervous system. This precursor then diversified, by cell-type functional segregation, into sister cell types that specialized in different subfunctions, evolving into separate photoreceptor cells, shading pigment cells (SPCs) or ciliated locomotor cells. Photoreceptor sensory cells and ciliated locomotor cells remained interconnected by newly evolving axons, giving rise to an early axonal circuit. In some evolutionary lines, residual functions prevailed in the specialized cell types that mirror the ancient multi-functionality, for instance, SPCs expressing an opsin as well as possessing rhabdomer-like microvilli, vestigial cilia and an axon. Functional segregation of cell types in eye evolution also explains the emergence of more elaborate photosensory–motor axonal circuits, with interneurons relaying the visual information.     

Evolution: What determines the rate of sequence evolution?

High rates of amino-acid sequence evolution have sometimes been considered to be diagnostic for genes undergoing adaptive change. However, two recent studies have shown that rapid evolution of amino-acid sequence can also be congruent with neutrality.     

Do proteins learn to evolve? The Hopfield network as a basis for the understanding of protein evolution

Correlations between amino-acid residues can be observed in sets of aligned protein sequences, and the analysis of their statistical and evolutionary significance and distribution has been thoroughly investigated. In this paper, we present a model based on such covariations in protein sequences in which the pairs of residues that have mutual influence combine to produce a system analogous to a Hopfield neural network. The emergent properties of such a network, such as soft failure and the connection between network architecture and stored memory, have close parallels in known proteins. This model suggests that an explanation for observed characters of proteins such as the diminution of function by substitutions distant from the active site, the existence of protein folds (superfolds) that can perform several functions based on one architecture, and structural and functional resilience to destabilizing substitutions might derive from their inherent network-like structure. This model may also provide a basis for mapping the relationship between structure, function and evolutionary history of a protein family, and thus be a powerful tool for rational engineering.     

The protein–protein interactions required for assembly of the Tn3 resolution synapse

The site-specific recombinase Tn3 resolvase initiates DNA strand exchange when two res recombination sites and six resolvase dimers interact to form a synapse. The detailed architecture of this intricate recombination machine remains unclear. We have clarified which of the potential dimer–dimer interactions are required for synapsis and recombination, using a novel complementation strategy that exploits a previously uncharacterized resolvase from Bartonella bacilliformis (“Bart”). Tn3 and Bart resolvases recognize different DNA motifs, via diverged C-terminal domains (CTDs). They also differ substantially at N-terminal domain (NTD) surfaces involved in dimerization and synapse assembly. We designed NTD-CTD hybrid proteins, and hybrid res sites containing both Tn3 and Bart dimer binding sites. Using these components in in vivo assays, we demonstrate that productive synapsis requires a specific “R” interface involving resolvase NTDs at all three dimer-binding sites in res. Synapses containing mixtures of wild-type Tn3 and Bart resolvase NTD dimers are recombination-defective, but activity can be restored by replacing patches of Tn3 resolvase R interface residues with Bart residues, or vice versa. We conclude that the Tn3/Bart family synapse is assembled exclusively by R interactions between resolvase dimers, except for the one special dimer–dimer interaction required for catalysis.     

Challenging the trade-off model for the evolution of virulence: is virulence management feasible?

Progress in understanding the evolution of infectious diseases has inspired proposals to manage the evolution of pathogen (including parasite) virulence. A common view is that social interventions that lower pathogen transmission will indirectly select lower virulence because of a trade-off between transmission and virulence. Here, we argue that there is little theoretical justification and no empirical evidence for this plan. Although a trade-off model might apply to some pathogens, the mechanism appears too weak for rapid selection of substantial changes in virulence. Direct selection against virulence itself might be a more rewarding approach to managing the evolution of virulence.     

A novel insight into the cost–benefit model for the evolution of botanical carnivory

Background The cost–benefit model for the evolution of botanical carnivory provides a conceptual framework for interpreting a wide range of comparative and experimental studies on carnivorous plants. This model assumes that the modified leaves called traps represent a significant cost for the plant, and this cost is outweighed by the benefits from increased nutrient uptake from prey, in terms of enhancing the rate of photosynthesis per unit leaf mass or area (A_N) in the microsites inhabited by carnivorous plants.Scope This review summarizes results from the classical interpretation of the cost–benefit model for evolution of botanical carnivory and highlights the costs and benefits of active trapping mechanisms, including water pumping, electrical signalling and accumulation of jasmonates. Novel alternative sequestration strategies (utilization of leaf litter and faeces) in carnivorous plants are also discussed in the context of the cost–benefit model.Conclusions Traps of carnivorous plants have lower A_N than leaves, and the leaves have higher A_N after feeding. Prey digestion, water pumping and electrical signalling represent a significant carbon cost (as an increased rate of respiration, R_D) for carnivorous plants. On the other hand, jasmonate accumulation during the digestive period and reprogramming of gene expression from growth and photosynthesis to prey digestion optimizes enzyme production in comparison with constitutive secretion. This inducibility may have evolved as a cost-saving strategy beneficial for carnivorous plants. The similarities between plant defence mechanisms and botanical carnivory are highlighted.     

The function of plant PR1 and other members of the CAP protein superfamily in plant–pathogen interactions

The pathogenesis-related (PR) proteins of plants have originally been identified as proteins that are strongly induced upon biotic and abiotic stress. These proteins fall into 17 distinct classes (PR1–PR17). The mode of action of most of these PR proteins has been well characterized, except for PR1, which belongs to a widespread superfamily of proteins that share a common CAP domain. Proteins of this family are not only expressed in plants but also in humans and in many different pathogens, including phytopathogenic nematodes and fungi. These proteins are associated with a diverse range of physiological functions. However, their precise mode of action has remained elusive. The importance of these proteins in immune defence is illustrated by the fact that PR1 overexpression in plants results in increased resistance against pathogens. However, PR1-like CAP proteins are also produced by pathogens and deletion of these genes results in reduced virulence, suggesting that CAP proteins can exert both defensive and offensive functions. Recent progress has revealed that plant PR1 is proteolytically cleaved to release a C-terminal CAPE1 peptide, which is sufficient to activate an immune response. The release of this signalling peptide is blocked by pathogenic effectors to evade immune defence. Moreover, plant PR1 forms complexes with other PR family members, including PR5, also known as thaumatin, and PR14, a lipid transfer protein, to enhance the host's immune response. Here, we discuss possible functions of PR1 proteins and their interactors, particularly in light of the fact that these proteins can bind lipids, which have important immune signalling functions.     

The protein sequence homology of γ-crystallins among major vertebrate classes and their DNA sequence homology to heat-shock protein genes

A systematic characterization of lens crystallins from five major classes of vertebrates was carried out by exclusion gel filtration, cation-exchange chromatography and N-terminal sequence determination. All crystallin fractions except that of γ-crystallin were found to be N-terminally blocked. γ-Crystallin is present in major classes of vertebrates except the bird, showing none, or decreased amounts, of this protein in chicken and duck lenses, respectively. N-Terminal sequence analysis of the purified γ-crystallin polypeptides showed extensive homology between different classes of vertebrates, supporting the close relatedness of this family of crystallin even from the evolutionarily distant species. Comparison of nucleotide sequences and their predicted amino acid sequences between γ-crystallins of carp and rat lenses and heat-shock proteins demonstrated partial sequence homology of the encoded polypeptides and striking homology at the gene level. The unexpected strong homology of complementary DNA (cDNA) lies in the regions coding for 40 N-terminal residues of carp γ-II, rat γ2-1, and the middle segments of 23,000- and 70,000-M _r heat-shock proteins. The optimal alignment of DNA sequences along these two segments shows about 50% homology. The percentage of protein sequence identity for the corresponding aligned segments is only 20%. The weak sequence homology at the protein level is also found between the invertebrate squid crystallin and rat γ-crystallin polypeptides. These results pointed to the possibility of unifying three major classes of vertebrate crystallins into one α/β/γ superfamily and corroborated the previous supposition that the existing crystallins in the animal kingdom are probably mutually interrelated, sharing a common ancestry.     

The structure of a truncated phosphoribosylanthranilate isomerase suggests a unified model for evolution of the (βα)8 barrel fold

The (βα)₈ barrel is one of the most common protein folds, and enzymes with this architecture display a remarkable range of catalytic activities. Many of these functions are associated with ancient metabolic pathways, and phylogenetic reconstructions suggest that the (βα)₈ barrel was one of the very first protein folds to emerge. Consequently, there is considerable interest in understanding the evolutionary processes that gave rise to this fold. In particular, much attention has been focused on the plausibility of (βα)₈ barrel evolution from homodimers of half barrels. However, we previously isolated a three-quarter-barrel-sized fragment of a (βα)₈ barrel, termed truncated phosphoribosylanthranilate isomerase (trPRAI), that is soluble and almost as thermostable as full-length N-(5′-phosphoribosyl)anthranilate isomerase (PRAI). Here, we report the NMR-derived structure of trPRAI. The subdomain is monomeric, is well ordered and adopts a native-like structure in solution. Side chains from strands β₁ (Glu3 and Lys5), β₂ (Tyr25) and β₆ (Lys122) of trPRAI repack to shield the hydrophobic core from the solvent. This result demonstrates that three-quarter barrels were viable intermediates in the evolution of the (βα)₈ barrel fold. We propose a unified model for (βα)₈ barrel evolution that combines our data, previously published work and plausible scenarios for the emergence of (initially error-prone) genetic systems. In this model, the earliest proto-cells contained diverse pools of part-barrel subdomains. Combinatorial assembly of these subdomains gave rise to many distinct lineages of (βα)₈ barrel proteins, that is, our model excludes the possibility that there was a single (βα)₈ barrel from which all present examples are descended.     

The Mid-Early Cretaceous as a turning point in the evolution of late Mesozoic rhynchonellids of the superfamily Rhynchonelloidea d’Orbigny, 1847

The study of rich rhynchonellid assemblage, collected by layers in the Early Cretaceous deposits of Dagestan, revealed sharp morphological changes of the assemblages at the Barremian-Aptian boundary; the shell exterior and almost all endoskeletal structures changed. The study of morphogenesis of the Late Mesozoic rhynchonellids revealed that boundary in the development of main shell structures during Middle Jurassic-Maastrichtian interval is also in the middle of Early Cretaceous.     

The cichlid–Cichlidogyrus network: a blueprint for a model system of parasite evolution

Hydrobiologia - Species interactions are a key aspect of evolutionary biology. Parasites, specifically, are drivers of the evolution of species communities and impact biosecurity and public health....