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PubMed2003

Comparative analysis of structural properties of the C-type-lectin-like domain (CTLD).

The superfamily of proteins containing the C-type-lectin-like domain (CTLD) is a group of abundant extracellular metazoan proteins characterized by evolutionary flexibility and functional versatility. Several CTLDs are also found in parasitic prokaryotes and viruses. The 37 distinct currently available CTLD structures demonstrate significant structural conservation despite low or undetectable sequence similarity. Our aim in this study was to perform an extensive comparative analysis of all available CTLD structures to establish the most conserved structural features of the fold, and to test and extend the early analysis of Drickamer. By implication, these features should be those critical for maintenance of integrity of the fold. By analyzing CTLD structures superimposed by several methods, we have established groups of conserved structural positions involved in fold maintenance but not in ligand binding; these are consistent with the fold's known functional flexibility. In addition to the well-recognized disulfide bridges, groups of conserved residues are involved in hydrophobic interactions stabilizing the core of the fold and the long loop region, and in an alpha2-beta1-beta5 polar interaction. Evaluation of the conclusions of the structure comparison study compared with alignments of all available human, mouse and Caenorhabditis elegans CTLD sequences showed that conservation patterns are preserved throughout the whole CTLD sequence space. Our observations provide an improved understanding of CTLD structure, and will help in identification of new CTLDs and the mechanisms that drive and constrain the coevolution of the structure and function of the fold.

Algorithms↗

PubMed2006

The evolution of ATPase activity in SMC proteins.

The SMC (structural maintenance of chromosomes) proteins are a highly conserved and ubiquitous family of ATPases, found in nearly all living organisms examined, where they play crucial roles in transmission of the hereditary material. However, the extent to which efficient ATP hydrolysis is required for SMC function has been a matter of some debate. Here we investigate the potential functional significance of ATP binding and hydrolysis in different eukaryotic SMC proteins, both by comparing the conservation of conserved ATPase motifs and by exploring potential coevolution between associated domains. In this way, we have been able to account for the reduced requirement for ATPase activity in cohesin's SMC3 and demonstrate the greater apparent conservation requirements for such activity in condensin SMC proteins. Finally, we explore possible interactions between the SMC and non-SMC components of the condensin complex that are required for full condensin activity and may modulate ATPase activity in the holocomplex.

Adenosine Triphosphatases↗

PubMed2000

Dialect change in resident killer whales: implications for vocal learning and cultural transmission.

Variation in vocal signals among populations and social groups of animals provides opportunities for the study of the mechanisms of behavioural change and their importance in generating and maintaining behavioural variation. We analysed two call types made by two matrilineal social groups of resident killer whales, Orcinus orca, over 12-13 years. We used a neural network-based index of acoustic similarity to identify mechanisms of call differentiation. A test for structural modification of the calls detected significant changes in one call type in both groups, but not in the other. For the modified call type, the rate of divergence between the two groups was significantly lower than the rate of modification within either group showing that calls were modified in a similar fashion in the two groups. An analysis of structural parameters detected no strong directionality in the change. The pattern of call modification could have been caused by maturational changes to the calls or, if killer whale dialects are learned behavioural traits, cultural drift in the structure of the calls together with horizontal transmission of modifications between the two groups. Such vocal matching between members of different matrilines would suggest that vocal learning is not limited to vertical transmission from mother to offspring, which has important implications for models of gene-culture coevolution. Copyright 2000 The Association for the Study of Animal Behaviour.

Journal Article↗

PubMed2001

Directed evolution of operon of trehalose-6-phosphate synthase/phosphatase from Escherichia coli.

Trehalose is a nonspecific protective agent for biomacromolecules. Trehalose-6-phosphate synthase (OtsA)/phosphatase (OtsB), which is encoded by the gene operon otsBA located at -42 of the Escherichia coli genome, is the main enzyme system that catalyzes the synthesis of trehalose in E. coli. We cloned the operon and modified it by directed evolution. Unlike in the previously reported work, we modified the whole operon and screened the positive mutant simultaneously. Thus we believe that the gene complex solves the negative effects between two enzymes if one of them diversifies its structure or functions and finds the form most suitable for trehalose synthesis. It thus mimics the natural process, in which the functional improvement of organisms is related to alterations in coordinated enzymes. The evolution procedure was carried out in a sequence of error-prone PCR, shuffling PCR, and then strict screening of the mutants. After screening of a library of more than 4000 colonies, about 15 positive colonies were analyzed, resulting in a higher concentration of trehalose than control. One of them, E. coli TS7, shows 12.3-fold higher trehalose synthesis ability than E. coli DH5alpha. In contrast, we introduced the cDNA sequence of the tps1 gene from Saccharomyces cerevisiae, which has 54% identity with the gene otsA, as one of the templates in shuffling PCR. By hybrid evolution and screening, we obtained 10 positive colonies with higher concentrations of trehalose than control. E. coli TS22 appears to have 5.3-fold higher trehalose synthesis ability than E. coli DH5alpha and 1.6-fold more than E. coli DEF3(pOTS11). This result demonstrated that coevolution and hybrid evolution, as powerful protocols in protein engineering, are effective in modifying enzyme. It indicates that repeating the process of genomic evolution in nature is feasible.

Directed Molecular Evolution↗

PubMed2001

Coparalogy: physical and functional clusterings in the human genome.

Two rounds of large-scale duplications are thought to have occurred in early vertebrate ancestry; this is now known as the "2R hypothesis." They have led to the constitution of subfamilies of paralogous genes. Chromosomal regions that contain present-day paralogs (paralogous regions or paralogons) have been identified in mammals. We show that sets of paralogons (PGs) can be assembled in a tentative "human genome paralogy map" that includes all autosomes and X. A total of 14 PGs, containing more than 1600 genes, were assembled in this paralogy map. Genes that belong to the same PG are coparalogs. We show that identification of coparalogy can be used (i) to broaden data on gene mapping, (ii) to identify physical gene clusters that derive from early cis-duplications, and (iii) to speculate on coevolution and coregulation of genes sharing a common structure or function (functional clusters). Thus, coparalogy analyses should parallel phylogenetic analyses and can help draw hypotheses on gene and genome evolution.

Chromosome Mapping↗

PubMed2000

Individual- and population-based diversity in restriction-modification systems.

Restriction-modification (RM) systems are cognate gene complexes that code for an endonuclease and a methylase. They are often thought to have developed in bacteria as protection against invading genetic material, e.g., phage DNA. The high diversity of RM systems, as observed in nature, is often ascribed to the coevolution of RM systems (which 'invent' novel types) and phages. However, the extent to which phages are insensitive to RM systems casts doubts on the effectiveness of RM systems as protection against infection and thereby on the reason for the diversity of RM systems. We present an eco-evolutionary model in order to study the evolution of the diversity of RM systems. The model predicts that in general diversity of RM systems is high. More importantly, the diversity of the RM systems is expressed either at the individual level or at the population level. In the first case all individuals carry RM systems of all sequence specificities, whereas in the second case they carry only one RM system or no RM systems at all. Nevertheless, in the second case the same number of sequence specificities are present in the population.

Bacteria↗

PubMed1997

Evolution of a fungal regulatory gene family: the Zn(II)2Cys6 binuclear cluster DNA binding motif.

The coevolution of DNA binding proteins and their cognate binding sites is essential for the maintenance of function. As a result, comparison of DNA binding proteins of unknown function in one species with characterized DNA binding proteins in another can identify potential targets and functions. The Zn(II)2Cys6 (or C6 zinc) binuclear cluster DNA binding domain has thus far been identified exclusively in fungal proteins, generally transcriptional regulators, and there are more than 80 known or predicted proteins which contain this motif, the best characterized of which are GAL4, PPR1, LEU3, HAP1, LAC9, and PUT3. Here we review all known proteins containing the Zn(II)2Cys6 motif, along with their function, DNA binding, dimerization, and zinc(II) coordination properties and DNA binding sites. In addition, we have identified all of the Zn(II)2Cys6 motif-containing proteins in the sequence databases, including a large number with unknown function from the completed Saccharomyces cerevisiae and ongoing Schizosaccharomyces pombe genome projects, and examined the phylogenetic relationships of all the Zn(II)2Cys6 motifs from these proteins. Based on these relationships, we have assigned potential functions to a number of these unknown proteins.

Base Sequence↗

PubMed1997

Phenotypic heterogeneity of mutational changes at a conserved nucleotide in 16 S ribosomal RNA.

RNA sites that contain unpaired or mismatched nucleotides can be interaction sites for other macromolecules. C1054, a virtually universally conserved nucleotide in the 16 S (small subunit) ribosomal RNA of Escherichia coli, is part of a highly conserved bulge in helix 34, which has been located at the decoding site of the ribosome. This helix has been implicated in several translational events, including peptide chain termination and decoding accuracy. Here, we observed interesting differences in phenotype associated with the three base substitutions at, and the deletion of, nucleotide C1054. The phenotypes examined include suppression of nonsense codons on different media and at different temperatures, lethality conditioned by temperature and level of expression of the mutant rRNA, ribosome profiles upon centrifugation through sucrose density gradients, association of mutant 30 S subunits with 50 S subunits, and effects on the action of tRNA suppressor mutants. Some of our findings contradict previously reported properties of individual mutants. Particularly notable is our finding that the first reported 16 S rRNA suppressor of UGA mutations was not a C1054 deletion but rather the base substitution C1054A. After constructing deltaC1054 by site-directed mutagenesis, we observed, among other differences, that it does not suppress any of the trpA mutations previously reported to be suppressed by the original UGA suppressor. In general, our results are consistent with the suggestion that the termination codon readthrough effects of mutations at nucleotide 1054 are the result of defects in peptide chain termination rather than of decreases in general translational accuracy. The phenotypic heterogeneity associated with different mutations at this one nucleotide position may be related to the mechanisms of involvement of this nucleotide, the two-nucleotide bulge, and/or helix 34 in particular translational events. In particular, previous indications from other laboratories of conformational changes associated with this region are consistent with differential effects of 1054 mutations on RNA-RNA or RNA-protein interactions. Finally, the association of a variety of phenotypes with different changes at the same nucleotide may eventually shed light on speculations about the coevolution of parts of ribosomal RNA with other translational macromolecules.

Base Sequence↗

PubMed2001

Analysis of the interaction between the eukaryotic chaperonin CCT and its substrates actin and tubulin.

Two mechanisms have thus far been characterized for the assistance by chaperonins of the folding of other proteins. The first and best described is that of the prokaryotic chaperonin GroEL, which interacts with a large spectrum of proteins. GroEL uses a nonspecific mechanism by which any conformation of practically any unfolded polypeptide interacts with it through exposed, hydrophobic residues. ATP binding liberates the substrate in the GroEL cavity where it is given a chance to fold. A second mechanism has been described for the eukaryotic chaperonin CCT, which interacts mainly with the cytoskeletal proteins actin and tubulin. Cryoelectron microscopy and biochemical studies have revealed that both of these proteins interact with CCT in quasi-native, defined conformations. Here we have performed a detailed study of the docking of the actin and tubulin molecules extracted from their corresponding CCT:substrate complexes obtained from cryoelectron microscopy and image processing to localize certain regions in actin and tubulin that are involved in the interaction with CCT. These regions of actin and tubulin, which are not present in their prokaryotic counterparts FtsA and FtsZ, are involved in the polymerization of the two cytoskeletal proteins. These findings suggest coevolution of CCT with actin and tubulin in order to counteract the folding problems associated with the generation in these two cytoskeletal protein families of new domains involved in their polymerization.

Actins↗

PubMed1994

Size effects in Kauffman type evolution for rugged fitness landscapes.

Millions of sites are simulated in an NK fitness model of evolution and coevolution. We find a logarithmic size dependence of the number of hill-climbing iterations needed to reach a local fitness optimum (Nash equilibrium). We also check for chaotic behavior and determine the size of the damage clouds or avalanches. Random noise (simulated annealing) is shown to increase appreciably the fitness.

Algorithms↗

PubMed1995

Evolutionary cycling in predator-prey interactions: population dynamics and the red queen.

This paper describes the coevolution of phenotypes in a community comprising a population of predators and of prey. It is shown that evolutionary cycling is a likely outcome of the process. The dynamical systems on which this description is based are constructed from microscopic stochastic birth and death events, together with a process of random mutation. Births and deaths are caused in part by phenotype-dependent interactions between predator and prey individuals and therefore generate natural selection. Three outcomes of evolution are demonstrated. A community may evolve to a state at which the predator becomes extinct, or to one at which the species coexist with constant phenotypic values, or the species may coexist with cyclic changes in phenotypic values. The last outcome corresponds to a Red Queen dynamic, in which the selection pressures arising from the predator-prey interaction cause the species to evolve without ever reaching an equilibrium phenotypic state. The Red Queen dynamic requires an intermediate harvesting efficiency of the prey by the predator and sufficiently high evolutionary rate constant of the prey, and is robust when the model is made stochastic and phenotypically polymorphic. A cyclic outcome lies outside the contemporary focus on evolutionary equilibria, and argues for an extension to a dynamical framework for describing the asymptotic states of evolution.

Animals↗

PubMed1997

Mutation rates as adaptations.

In order to better understand life, it is helpful to look beyond the envelop of life as we know it. A simple model of coevolution was implemented with the addition of a gene for the mutation rate of the individual. This allowed the mutation rate itself to evolve in a lineage. The model shows that when the individuals interact in a sort of zero-sum game, the lineages maintain relatively high mutation rates. However, when individuals engage in interactions that have greater consequences for one individual in the interaction than the other, lineages tend to evolve relatively low mutation rates. This model suggests that one possible cause for differential mutation rates across genes may be the coevolutionary pressure of the various forms of interactions with other genes.

Adaptation, Physiological↗

PubMed1997

On the origin of the genetic code.

The main theories which have been suggested to explain the origin of genetic code organization are discussed. The coevolution theory, which considers the genetic code as a map of the biosynthetic relationships between amino acids, seems to be based on a mechanism that links it closely to certain stages of the origin of metabolism, which makes it preferable to other theories proposed as explanations of genetic code origin. Relationships, incompatibilities and compromises between the various theories are highlighted and these seem to indicate a certain lack of clarity in this field of research.

Animals↗

PubMed1997

A model of mass extinction.

In the last few years a number of authors have suggested that evolution may be a so-called self-organized critical phenomenon, and that critical processes might have a significant effect on the dynamics of ecosystems. In particular it has been suggested that mass extinction may arise through a purely biotic mechanism as the result of "coevolutionary avalanches". In this paper we first explore the empirical evidence which has been put forward in favor of this conclusion. The data center principally around the existence of power-law functional forms in the distribution of the sizes of extinction events and other quantities. We then propose a new mathematical model of mass extinction which does not rely on coevolutionary effects and in which extinction is caused entirely by the action of environmental stress on species. In combination with a simple model of species adaption we show that this process can account for all the observed data without the need to invoke coevolution and critical processes. The model also makes some independent predictions, such as the existence of "aftershock" extinctions in the aftermath of large mass extinction events, which should in theory be testable against the fossil record.

Animals↗

PubMed1998

Evolution of transmission bias in cultural inheritance.

Evolution of transmission bias in cultural inheritance is investigated using simple models of cultural selection. Conventional models of cultural transmission describe cultural changes by incorporating transmission bias and non-vertical pathways into the ordinary population genetic framework. The methodology has been successful in understanding cultural changes in terms of natural selection, but it is difficult to see from the theoretical framework how biased transmission in favor of maladaptive traits might have evolved. To show that ordinary cultural processes lead at times to the evolution of a preference that favors a deleterious cultural variant, this study presents an alternative model of cultural transmission, where cultural elements are transmitted in a manner more like infections in epidemiological transmission. An ordinary equilibrium analysis indicates that, under certain conditions, runaway dynamics emerges and the coevolution of a maladaptive cultural variant and an associated preference in favor of the maladaptive variant is observed. If the preference of an individual does not change during its ontogeny (e.g., if it is transmitted genetically), however, then cultural selection alone does not produce such runaway dynamics, and only those preferences that favor adaptive variants should eventually evolve. Since cultural processes may at times result in a reduction in the fitness of individuals, simplistic adaptive interpretations of culture are unconvincing without detailed specification of the cultural processes involved. Moreover, cultural runaway of this kind may help to explain the existence of traits that are apparently maladaptive at the individual level but may be advantageous for the group. Inferences are also made regarding the observed differences between human and non-human social information transfer.

Adaptation, Physiological↗

PubMed1998

Reflections on the origin of the genetic code: a hypothesis.

The origin of the organisation of the genetic code reflects both the biosynthetic relationships between amino acids and the physicochemical interactions between these and anticodons; moreover, these two forces do not act independently. It must therefore be explained why it is simultaneously true that the anticodons of product amino acids were assigned prior to their biosynthetic appearance and that physicochemical correlations must exist between anticodons and amino acids. This gives rise to difficulties of interpretation, even of a more general nature, in the theories that have been proposed to explain the origin of the genetic code; a hypothesis is thus presented in this manuscript. In particular, the hypothesis suggests that RNA hairpin structures, the ancestors of tRNAs, housing anticodon-like nucleotides in the stem were charged with precursor amino acids. As the precursor amino acids gradually developed into product amino acids, a coevolution came into being between the development of amino acids and that of anticodons, with a concomitant formation of the complete tRNA molecule thought direct duplication of the hairpin structures. All this led to the definition of the genetic code organisation. Furthermore, this made it possible for the evolving anticodons to select the emerging product amino acids, which the hypothesis therefore considers to be unspecified in the initial phase of genetic code evolution but which were selected also because of their ability to interact with anticodons. In this way the main obstacle to interpretation is removed. Fossils of these events can now be observed in some amino acid-modified nucleosides specifically located in the tRNA anticodon loops. This is all presented in the framework of a general discussion of the ideas and data in favour of a late origin of the genetic code, as opposed to an early origin in the context of the theories proposed to explain the origin of the genetic code organisation.

Amino Acids↗

PubMed1998

Mafia behaviour and the evolution of facultative virulence.

Some organisms enforce "maladaptive" behaviours on others of the same or different species by imposing costs in the absence of compliance. Such enforcement is used by the enforcer to obtain benefits in the possession of the enforced individual. This mechanism is known as mafia behaviour in humans, but may be widespread in parasite-host relationships in nature, from the cellular level to societies. In this paper we describe the evolution of such mafia mechanisms, and we propose a fuzzy logic model where the mafia mechanism is based on enforcement of hosts by exponentially increasing the cost of resistance to the parasite. The benefits of host resistance can be counteracted by parasite virulence, or even a decrease in response to an increment in its resistance. This parasite response to the host defence increment can be used for the parasite to teach the host that it is better to pay part of its benefits than increase its extremely costly defence. This model differs from others because it takes into account the evolution of host defence related to the evolution of parasite virulence (host-parasite coevolution) and points out an optimum in host defence related to the facultative virulence of the parasite. We provide several potential examples of facultative virulence depending on the antiparasite responses of hosts, and we suggest that this kind of mafia behaviour may be a widespread mechanism in biological processes at a number of different levels.

Animals↗

PubMed1998

Coevolutionary chase in two-species systems with applications to mimicry.

We study a general dynamical model describing coevolution of two haploid populations with two alleles at a single locus under weak linear symmetric frequency-dependent selection. A novel and more realistic element of our modeling approach is that both species are allowed to evolve. We analyse conditions for "evolutionary chase" between two phenotypically similar species in which one species evolves to decrease its resemblance with the other species while this other species evolves to increase its resemblance with the first species. We apply our results to a series of simple population genetics models describing classical Müllerian and Batesian mimicries as well as intermediate cases. We show that one of the most important factors influencing the plausibility of non-equilibrium dynamics in systems of mimicry is the relationship between the strength of between-species and within-species interactions. This indicates that this relationship should be the focus of both experimental and theoretical work. Our results suggest that systematic studies of frequencies of different mimicry morphs through time may be very useful.

Animals↗