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PubMed2006

Metabolic analysis of adaptive evolution for in silico-designed lactate-producing strains.

Experimental evolution is now frequently applied to many biological systems to achieve desired objectives. To obtain optimized performance for metabolite production, a successful strategy has been recently developed that couples metabolic engineering techniques with laboratory evolution of microorganisms. Previously, we reported the growth characteristics of three lactate-producing, adaptively evolved Escherichia coli mutant strains designed by the OptKnock computational algorithm. Here, we describe the use of (13)C-labeled experiments and mass distribution measurements to study the evolutionary effects on the fluxome of these differently designed strains. Metabolic flux ratios and intracellular flux distributions as well as physiological data were used to elucidate metabolic responses over the course of adaptive evolution and metabolic differences among strains. The study of 3 unevolved and 12 evolved engineered strains as well as a wild-type strain suggests that evolution resulted in remarkable improvements in both substrate utilization rate and the proportion of glycolytic flux to total glucose utilization flux. Among three strain designs, the most significant increases in the fraction of glucose catabolized through glycolysis (>50%) and the glycolytic fluxes (>twofold) were observed in phosphotransacetylase and phosphofructokinase 1 (PFK1) double deletion (pta- pfkA) strains, which were likely attributed to the dramatic evolutionary increase in gene expression and catalytic activity of the minor PFK encoded by pfkB. These fluxomic studies also revealed the important role of acetate synthetic pathway in anaerobic lactate production. Moreover, flux analysis suggested that independent of genetic background, optimal relative flux distributions in cells could be achieved faster than physiological parameters such as nutrient utilization rate.

Acetate-CoA Ligase↗

PubMed2007

Can knowledge of developmental processes illuminate the evolution of parental care?

There are two levels of investigation for elucidating the evolution of parental behavior. The macro level focuses on how parental behavior can evolve as an aspect of reproduction. The micro level focuses on how species variations in parental behavior evolve. Recently, modern evolutionary biology has turned to developmental biology as a source for information about how trait variability (the substrate upon which natural selection and other evolutionary mechanisms can operate) can emerge during development (called "evo-devo"). Application of this evo-devo approach to the phenomenon of parental behavior requires identification of those mechanisms that produce variations in developmental pathways leading to parental behavior. It is these variations that provide the phenotypes for the potential evolution of different parental behavior systems. Variations in rodent maternal behavior affect the development of the HPA and HPG axes in their offspring. These mechanisms are examined to reveal how such developmental variations could underlie the evolution of biparental behavior. Knowledge of the developmental mechanisms responsible for species variations in mammalian parental behavior systems may provide insight into those mechanisms that may have been involved in the evolution of parental behavior itself.

Animals↗

PubMed2005

Fishing for the secrets of vertebrate evolution in threespine sticklebacks.

The threespine stickleback (Gasterosteus aculeatus) is rapidly emerging as a new model genetic system to study questions at the interface of evolution and development. The relatively rapid and recent diversification of this small teleost fish, combined with the development of genetic and genomic tools for this fish, provides an unprecedented opportunity to identify the genetic and molecular basis of morphological variation in natural populations of vertebrates. Recently, the genes underlying two different adaptive morphological traits in stickleback have been identified. This work has provided answers to four longstanding questions in the field of evolution and development: (1) How many genes underlie morphological variation in natural populations? (2) What are the genes that underlie morphological variation in natural populations? (3) Do coding or regulatory mutations underlie morphological evolution? (4) What is the molecular and genetic basis of parallel morphological evolution? Because stickleback populations also display natural variation in morphology, life history, physiology, and behavior, extending the approaches used to identify the genetic basis of morphological variation in sticklebacks to other phenotypes is sure to yield further important insights into the genetic and developmental basis of diversity in natural populations.

Adaptation, Biological↗

PubMed2001

Multivariate analyses of genomic imbalances in solid tumors reveal distinct and converging pathways of karyotypic evolution.

A total of 3,016 malignant solid tumors (kidney, colorectal, breast, head and neck, ovarian, and lung carcinomas, neuroglial tumors, malignant melanoma, and testicular germ cell tumors) were selected for statistical analyses regarding karyotypic evolution. Genomic imbalances, i.e., net gains and losses, present in more than 5% of each tumor type were identified. Individual tumors were then classified with respect to absence or presence of these imbalances. To analyze for possible patterns of correlated imbalances, principal component analyses (PCA) were performed. Furthermore, algorithms were developed to analyze the temporal order of the imbalances, as well as the possible selection for early or late appearance in the karyotypic evolution. By analyzing the temporal order of imbalances common to many tumor types, a general order for nine of these emerged, namely, +7, -3p, -6q, -1p, -8p, -17p, -9p, -18, and -22. The distributions of the number of imbalances per case revealed a geometrical distribution, ranging from one to nine imbalances per tumor, in the majority of the tumor types. In tumor types in which cases with a high number of imbalances per case were frequent, notably head and neck, ovarian, and lung carcinomas, the overall distributions were bimodal, indicating the presence of two modes of chromosome evolution. By combining data from the PCA with the temporal analyses, it was possible to identify karyotypic pathways. It was found that the majority of the tumor types displayed more than one cytogenetic route, but, as the karyotypic evolution continued, these converged to a common pathway.

Allelic Imbalance↗

PubMed2004

Libbie Henrietta Hyman (1888-1969): from developmental mechanics to the evolution of animal body plans.

Libbie Hyman is the most influential comparative invertebrate zoologist of the 20th century in the English-speaking world. During the first part of her career Hyman conducted experimental research on the metabolic and developmental physiology of a host of invertebrates and vertebrate embryos. One important aim of these studies was to elucidate the hidden processes of morphogenesis. Some of the papers from this early phase of Hyman's career already contain the seeds for her subsequent occupation with comparative embryology and morphology to address questions about animal body plan evolution and metazoan phylogeny. Hyman's views on invertebrate evolution and phylogeny have become widely incorporated into textbooks, and until very recently Hyman's ideas have been equated with 'traditional' or 'classical' views on animal evolution. Hyman's enduring fame and significance for modern evo-devo is primarily based upon her magisterial six-volume series The Invertebrates, which is the most encompassing single-author synthesis of invertebrate structure and development of the 20th century. In The Invertebrates Hyman addressed numerous questions about the evolution of animal body plans and metazoan phylogeny that are nowadays core items on the research agenda of evo-devo. In addition, Hyman had a lasting influence on teaching with the publication of her widely used laboratory manuals for elementary zoology, and especially comparative vertebrate anatomy.

Animals↗

PubMed2005

Molecular evolution of evolutionary novelties: the vagina and uterus of therian mammals.

Innovations are an integral part of the evolutionary process if we accept the fact that more complex organisms derived from anatomically simple ones. All major taxa are distinguished not only by their closer genealogical relatedness relative to other species but also by the possession of novel anatomical and physiological features. The question is whether the origin of these novel characters can be simply understood as adaptations, like all other phenotypic differences that arise by natural selection, or whether the origin of these characters requires more profound genetic changes. In this paper, we argue that innovations constitute a distinct class of evolutionary processes that require a research program complementary to the study of adaptation. The distinguishing feature of innovations is the origin of novel organ identity gene functions specific to the novel character. By implication, research into the origin of novel characters has to identify the developmental regulatory links that were involved in the evolution of these characters. We suggest that novel regulatory links will include the evolution of cis-regulatory elements as well as novel protein-protein interactions among transcription factor proteins. The latter hypothesis suggests that innovations should leave a trace in the evolution of the protein coding regions of transcription factor genes. We illustrate this idea with results on the evolution of HoxA-11 and HoxA-13 in the stem lineage of placental mammals. These genes are essential for female reproductive tract development and function. We show that, as predicted, these genes experience strong directional selection in the stem lineage of placental mammals and that these amino acid substitutions affect residues at the surface of the protein, consistent with their expected role in protein-protein interactions. We conclude that a careful analysis of sequence variation in developmental genes can aid in testing which developmental changes were instrumental in the origin of novel morphological characters.

Animals↗

PubMed2006

The evolution of immune mechanisms.

From early on in evolution, organisms have had to protect themselves from pathogens. Mechanisms for discriminating "self" from "non-self" evolved to accomplish this task, launching a long history of host-pathogen co-evolution. Evolution of mechanisms of immune defense has resulted in a variety of strategies. Even unicellular organisms have rich arsenals of mechanisms for protection, such as restriction endonucleases, antimicrobial peptides, and RNA interference. In multicellular organisms, specialized immune cells have evolved, capable of recognition, phagocytosis, and killing of foreign cells as well as removing their own cells changed by damage, senescence, infection, or cancer. Additional humoral factors, such as the complement cascade, have developed that co-operate with cellular immunity in fighting infection and maintaining homeostasis. Defensive mechanisms based on germline-encoded receptors constitute a system known as innate immunity. In jaw vertebrates, this system is supplemented with a second system, adaptive immunity, which in contrast to innate immunity is based on diversification of immune receptors and on immunological memory in each individual.Usually, each newly evolved defense mechanism did not replace the previous one, but supplemented it, resulting in a layered structure of the immune system. The immune system is not one system but rather a sophisticated network of various defensive mechanisms operating on different levels, ranging from mechanisms common for every cell in the body to specialized immune cells and responses at the level of the whole organism. Adaptive changes in pathogens have shaped the evolution of the immune system at all levels.

Adaptation, Biological↗

PubMed1994

Evolution rate of hepatitis delta virus RNA isolated in Taiwan.

The complete RNA sequences of hepatitis delta viruses (HDV) isolated at 3 years apart from a chronic delta hepatitis patient in Taiwan were determined. The sequence analysis showed an overall evolution rate of 3.18 x 10(-3) substitutions/nucleotide/year. The evolution rates in different parts of HDV RNA varied. The hypervariable region evolved faster (4.55 x 10(-3) substitutions/nucleotide/year) than the hepatitis delta antigen (HDAg)-coding region (2.60 x 10(-3) substitutions/nucleotide/year) and the autocatalytic region (1.11 x 10(-3) substitutions/nucleotide/year). These data are compatible with the previous finding that the hypervariable region is more divergent than the HDAg-coding region and the autocatalytic regions among the HDV isolates from different geographic areas. No substitution was found in the four previously identified conserved domains of HDV RNA, further confirming their functional importance in viral replication. The evolution rate of this HDV RNA is higher than that determined from the partial RNA sequences of two Japanese HDV isolates and similar to that found in a Lebanon isolate. Further, it was found that this HDV RNA retained the same microheterogeneities at 15 nucleotide positions detected in the RNA 3 years earlier. It is concluded that HDV RNA in patients' serum is extremely heterogeneous, and that the nucleotide substitutions in certain nucleotide positions likely have conferred evolutionary advantages for HDV. Viral sequence evolution is a possible mechanism for chronic HDV infection.

Adult↗

PubMed2001

From cofactor to enzymes. The molecular evolution of pyridoxal-5'-phosphate-dependent enzymes.

The pyridoxal-5'-phosphate (vitamin B(6))-dependent enzymes that act on amino acid substrates have multiple evolutionary origins. Thus, the common mechanistic features of B(6) enzymes are not accidental historical traits but reflect evolutionary or chemical necessities. The B(6) enzymes belong to four independent evolutionary lineages of paralogous proteins, of which the alpha family (with aspartate aminotransferase as the prototype enzyme) is by far the largest and most diverse. The considerably smaller beta family (tryptophan synthase beta as the prototype enzyme) is structurally and functionally more homogenous. Both the D-alanine aminotransferase family and the alanine racemase family consist of only a few enzymes. The primordial pyridoxal-5'-phosphate-dependent protein catalysts apparently first diverged into reaction-specific protoenzymes, which then diverged further by specializing for substrate specificity. Aminotransferases as well as amino acid decarboxylases are found in two different evolutionary lineages, providing examples of convergent enzyme evolution. The functional specialization of most B(6) enzymes seems to have already occurred in the universal ancestor cell before the divergence of eukaryotes, archebacteria, and eubacteria 1500 million years ago. Pyridoxal-5'-phosphate must have emerged very early in biological evolution; conceivably, metal ions and organic cofactors were the first biological catalysts. To simulate particular steps of molecular evolution, both the substrate and reaction specificity of existent B(6) enzymes were changed by substitution of active-site residues, and monoclonal pyridoxal-5'-phosphate-dependent catalytic antibodies were produced with selection criteria that might have been operative in the evolution of protein-assisted pyridoxal catalysis.

Amino Acid Isomerases↗

PubMed1993

Evolution and polymorphism of poliovirus genomes.

The three poliovirus serotypes are very stable. Breakthrough of the serotype barrier has never been observed in the natural evolution of poliovirus. This serotype stability contrasts with the high level of genomic and phenotypic variability that occurs within the bounds of serotype. The efficient control of poliomyelitis by immunization is based upon type-specific immunity and serotype stability. The development of attenuated strains by Albert Sabin was possible because of the high variability of poliovirus genomes. The three Sabin strains, one for each serotype, were selected as variants of non-attenuated wild polioviruses, and each represents a unique poliovirus genotype. A consequence of poliovirus variability is the polymorphic character of its genome. This polymorphism makes possible the identification of poliovirus genotypes upon which studies on poliovirus evolution, virologic surveillance, and poliomyelitis diagnostics are based. The antigenic and genomic peculiarities of the Sabin strains are used to distinguish them from wild polioviruses among field isolates. The mechanisms of poliovirus variation and their significance to the evolution of both wild and vaccine poliovirus strains are the subjects of this article. The natural evolution of polioviruses is discussed in the context of the global initiative to eradicate poliomyelitis, which relies on the worldwide use of Sabin's vaccine.

Animals↗

PubMed2002

The evolution of chordate neural segmentation.

Amphioxus is the closest relative to vertebrates but lacks key vertebrate characters, like rhombomeres, neural crest cells, and the cartilaginous endoskeleton. This reflects major differences in the developmental patterning of neural and mesodermal structures between basal chordates and vertebrates. Here, we analyse the expression pattern of an amphioxus FoxB ortholog and an amphioxus single-minded ortholog to gain insight into the evolution of vertebrate neural segmentation. AmphiFoxB expression shows cryptic segmentation of the cerebral vesicle and hindbrain, suggesting that neuromeric segmentation of the chordate neural tube arose before the origin of the vertebrates. In the forebrain, AmphiFoxB expression combined with AmphiSim and other amphioxus gene expression patterns shows that the cerebral vesicle is divided into several distinct domains: we propose homology between these domains and the subdivided diencephalon and midbrain of vertebrates. In the Hox-expressing region of the amphioxus neural tube that is homologous to the vertebrate hindbrain, AmphiFoxB shows the presence of repeated blocks of cells along the anterior-posterior axis, each aligned with a somite. This and other data lead us to propose a model for the evolution of vertebrate rhombomeric segmentation, in which rhombomere evolution involved the transfer of mechanisms regulating neural segmentation from vertical induction by underlying segmented mesoderm to horizontal induction by graded retinoic acid signalling. A consequence of this would have been that segmentation of vertebrate head mesoderm would no longer have been required, paving the way for the evolution of the unsegmented head mesoderm seen in living vertebrates.

Amino Acid Sequence↗

PubMed1996

Specialization of the DNA-cleaving activity of a group I ribozyme through in vitro evolution.

In an earlier study, an in vitro evolution procedure was applied to a large population of variants of the Tetrahymena group I ribozyme to obtain individuals with a 10(5)-fold improved ability to cleave a target single-stranded DNA substrate under simulated physiological conditions. The evolved ribozymes also showed a twofold improvement, compared to the wild-type, in their ability to cleave a single-stranded RNA substrate. Here, we report continuation of the in vitro evolution process using a new selection strategy to achieve both enhanced DNA and diminished RNA-cleavage activity. Our strategy combines a positive selection for DNA cleavage with a negative selection against RNA binding. After 36 "generations" of in vitro evolution, the evolved population showed an approximately 100-fold increase in the ratio of DNA to RNA-cleavage activity. Site-directed mutagenesis experiments confirmed the selective advantage of two covarying mutations within the catalytic core of the ribozyme that are largely responsible for this modified behavior. The population of ribozymes has now undergone a total of 63 successive generations of evolution, resulting in an average of 28 mutations relative to the wild-type that are responsible for the altered phenotype.

Animals↗

PubMed1996

Genetic conflicts and the paradox of sex determination: three paths to the evolution of female intersexuality in a mammal.

That sex determining systems ever change is paradoxical but can be explained by noting that conflict between selfish elements and their modifiers will often cause a shift in sex determining strategy. The evolution of the novel sex determining system of moles (Talpa europaea and T. occidentalis) may, we argue, be an example of just such a process. Three different models for the evolution of female intersexuality are presented. These all attempt to account for (1) the fact that a few years ago populations of moles had high frequencies of sterile XX individuals that were either morphologically male or intersex (other XX individuals were normal females) and (2) that presently, the XX individuals in the same population are exclusively fertile intersexes that are functionally female; i.e. have follicle producing ovotestes. This case history is compared to that of the wood lemming and two similarities are discussed. First, in both cases it is noted that one end product could be approached from different routes. Second, selfish elements may be involved in the evolution of both systems. In general, it is suggested that XY sex determination, far from being resilient to evolutionary change, is vulnerable to take-over by selfish elements. This is particularly the case in mammals in which transplacental interactions could allow manipulation of sex determination in one foetus by another. This, we also suggest, is a good candidate explanation for the evolution of novel sex determination in Talpa.

Animals↗

PubMed1997

Major "anastrophes" in the origin and early evolution of biological energy conversion.

The metabolism of living organisms has long been usefully divided into anabolism and catabolism. Anabolism is constructive, being concerned with the assembly of complex molecules, whereas catabolism is destructive in the sense that it involves the degradation of molecules. In addition to the well-known word catastrophe for sudden, drastic destruction and its consequences, it has been found practical to introduce in the evolutionary context the word "anastrophe" (an old greek word for turning back, in the opposite direction-from anastrephein, where ana = back and strephein = to turn) to cover sudden, drastic constructive events and their consequences. Mutations in genes and genomes giving selective advantage to an organism are typical anastrophic events. A single site mutation in a gene coding for a protein may be good, neutral or bad, or anastrophic, neutral or catastrophic, respectively, for the organism. The consequence of an anastrophic mutation may be a decisive first step on the long way to a new species, whereas a catastrophic mutation may lead to major cell damage or death. This example of the use of the anastrophe concept in biological evolution leads to the question about its applicability to other parts and paths of the cosmic evolutionary process, such as physical, chemical, social and cultural evolution. Here it will be mainly considered in connection with the energy conversion aspects of the chemical evolution leading to the origin of life and of the subsequent early biological evolution. More specifically, it will be attempted to describe possible major anastrophes in energy conversion both before and after the first occurrence of life on earth.

Animals↗

PubMed1998

Non-equilibrium thermodynamics of molecular evolution.

The evolution of the information complexity of a large database of protein sequences is investigated. The information entropy for protein sequences is determined from their algorithmic complexity and is found to change with evolutionary time at a constant rate. The information content of changed residues is always lower than the content of conserved residues. This indicates that sequences are becoming less random throughout evolution. It also shows that the system is being driven toward minimal complexity production. The change in information content per amino acid substitution is virtually identical for all the protein sequences studied. These results are interpreted with a statistical mechanical theory that ties sequence information to the thermodynamics of protein structure. Sequence evolution is viewed as a means to drive the system to minimum thermodynamic entropy production in a stable, non-equilibrium state. This theory provides a physical framework for understanding molecular evolution and incorporates features of both the neutralist and selectionist models.

Amino Acid Sequence↗

PubMed2000

A classification of possible routes of Darwinian evolution.

A classification of four possible routes of Darwinian evolution is presented. These are serial direct evolution, parallel direct evolution, elimination of functional redundancy, and adoption from a different function. This classification provides a conceptual framework within which to investigate the accessibility by Darwinian evolution of complex biological structures.

Animals↗

PubMed2001

Promotion of evolution by intracellular coexistence of mutator and normal DNA polymerases.

The efficient evolution of a population requires both genetic diversity and stable reproduction of advantageous genotypes. The accuracy of DNA replication guarantees the stable reproduction, while errors during DNA replication produce the genetic diversity. Thus, one key to the promotion of evolution is inherent in DNA replication. In bacteria, replication forks progress bidirectionally from the single origin of replication on a genome. One replication fork contains two DNA polymerase molecules so that four DNA polymerases simultaneously carry out the replication of a genome. It is generally believed that the fidelity of the intracellular DNA polymerases is identical (parity strategy). To test this, we examined the effects of the intracellular coexistence of a mutator polymerase with low fidelity and a normal polymerase with high fidelity on adaptive evolution (disparity strategy). From the analysis using genetic algorithms based on the bacterial replication, it was found that the population using the disparity strategy could further expand its genetic diversity and preserve the advantageous genotypes more profoundly than the parity population. This strongly suggests that bacteria replicating with a disparity strategy may undergo rapid evolution, particularly during severe environmental changes. The implications of the conspicuous adaptability of Escherichia coli mutator strains are discussed in this context.

Animals↗

PubMed2002

A model of the early evolution of soma-to-germline feedback.

The V-genes of the immunoglobulin locus in vertebrates code for a part of the heavy and light chain variable regions of antibodies and are extremely variable. Steele (1979) has developed a theory that explains the evolution of adaptive immune response by a soma-to-germline flow of cDNAs derived from somatically mutated V-genes. Here we model the early evolution of soma-to-germline feedback in a population living in a changing viral environment in terms of the dynamics of an initially rare genetic modifier that controls transfer of V-genes to germ cells' DNA. It is shown that a modifier invades the population and creates a great variety of V-genes if the environment follows stepwise temporal changes, i.e. a soma-to-germline feedback machinery evolves in a population if newly derived V-alleles still play a role in protecting the population against foreign antigens in some following generations. The distribution of the age of V-genes evolves to a bell-shaped curve the width and the maximum of which depend mainly on selection strength. Two phases of modifier evolution are distinguished. In the first phase, the dynamics are slow while the number of different V-genes is small. In the second phase, when a sufficiently large number of different V-genes is created, the modifier increases faster in frequency. Linkage of V-genes and the modifier enhances the rate of evolution.

Animals↗