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Multiple von Neumann computers: an evolutionary approach to functional emergence.

A novel system composed of multiple von Neumann computers and an appropriate problem environment is proposed and simulated. Each computer has a memory to store the machine instruction program, and when a program is executed, a series of machine codes in the memory is sequentially decoded, leading to register operations in the central processing unit (CPU). By means of these operations, the computer not only can handle its generally used registers but also can read and write the environmental database. Simulation is driven by genetic algorithms (GAs) performed on the population of program memories. Mutation and crossover create program diversity in the memory, and selection facilitates the reproduction of appropriate programs. Through these evolutionary operations, advantageous combinations of machine codes are created and fixed in the population one by one, and the higher function, which enables the computer to calculate an appropriate number from the environment, finally emerges in the program memory. In the latter half of the article, the performance of GAs on this system is studied. Under different sets of parameters, the evolutionary speed, which is determined by the time until the domination of the final program, is examined and the conditions for faster evolution are clarified. At an intermediate mutation rate and at an intermediate population size, crossover helps create novel advantageous sets of machine codes and evidently accelerates optimization by GAs.

Algorithms↗

Bursts of nonsynonymous substitutions in HIV-1 evolution reveal instances of positive selection at conservative protein sites.

The fixation of a new allele can be driven by Darwinian positive selection or can be due to random genetic drift. Identifying instances of positive selection is a difficult task, because its impact is routinely obscured by the action of negative selection. The nature of the genetic code dictates that positive selection in favor of an amino acid replacement should often cause a burst of two or three nucleotide substitutions at a single codon site, because a large fraction of amino acid replacements cannot be achieved after just one nucleotide substitution. Here, we study pairs of successive nonsynonymous substitutions at one codon in the course of evolution of HIV-1 genes within HIV-1 populations inhabiting infected individuals. Such pairs are more numerous and more clumped than expected if different substitutions were independent and than what is observed for pairs of successive synonymous substitutions. Bursts of nonsynonymous substitutions in HIV-1 evolution cannot be explained by mutational biases and must, therefore, be due to positive selection. Both reversals, exact or imprecise, of fixed deleterious mutations and acquisitions of amino acids with new properties are responsible for the bursts. Temporal clumping is strongest at codon sites with a low overall rate of nonsynonymous evolution, implying that a substantial fraction of replacements of conservative amino acids are driven by positive selection. We identified many conservative sites of HIV-1 proteins that occasionally experience positive selection.

Amino Acid Substitution↗

Information Theory, Scaling Laws and the Thermodynamics of Evolution.

Renormalization symmetry and the Legendre transformation are imposed on a parametized form of ergodic source uncertainty, a widely-applied model for "languages" ranging from the spoken word to genetic codes. Using the Shannon-McMillan theorem to identify a duality between source uncertainty and free energy density, this procedure: (i) suggests that a punctuated "phase change" and resulting sudden fragmentation or coalescence should be the norm for "language"-based phenomena, particularly the transfer of "genetic" information within reproducing populations; (ii) gives a power law for that phase change near transition; (iii) provides a "disorder" construct similar to an entropy which may trigger higher degrees of punctuation in social systems than is suggested from simple physical analogs; and (iv) gives "equations of state" relating ensemble averages which should be observable within coalesced systems. The general formalism is explicitly applied to problems of speciation, coevolution and group selection, and comparison made with the work of Eigen and his associates.Copyright 1998 Academic Press Limited

Journal Article↗

Platyhelminth mitochondrial DNA: evidence for early evolutionary origin of a tRNA(serAGN) that contains a dihydrouridine arm replacement loop, and of serine-specifying AGA and AGG codons.

The nucleotide sequence of a segment of the mitochondrial DNA (mtDNA) molecule of the liver fluke Fasciola hepatica (phylum Platyhelminthes, class Trematoda) has been determined, within which have been identified the genes for tRNA(ala), tRNA(asp), respiratory chain NADH dehydrogenase subunit I (ND1), tRNA(asn), tRNA(pro), tRNA(ile), tRNA(lys), ND3, tRNA(serAGN), tRNA(trp), and cytochrome c oxidase subunit I (COI). The 11 genes are arranged in the order given and are all transcribed from the same strand of the molecule. The overall order of the F. hepatica mitochondrial genes differs from what is found in other metazoan mtDNAs. All of the sequenced tRNA genes except the one for tRNA(serAGN) can be folded into a secondary structure with four arms resembling most other metazoan mitochondrial tRNAs, rather than the tRNAs that contain a T psi C arm replacement loop, found in nematode mtDNAs. The F. hepatica mitochondrial tRNA(serAGN) gene contains a dihydrouridine arm replacement loop, as is the case in all other metazoan mtDNAs examined to date. AGA and AGG are found in the F. hepatica mitochondrial protein genes and both codons appear to specify serine. These findings concerning F. hepatica mtDNA indicate that both a dihydrouridine arm replacement loop-containing tRNA(serAGN) gene and the use of AGA and AGG codons to specify serine must first have occurred very early in, or before, the evolution of metazoa.

Amino Acid Sequence↗

Uncovering the genomic landscape of Mycobacterium bovis in Wales.

Bovine tuberculosis (bTB), caused by the bacterium Mycobacterium bovis, is one of the most pressing animal health issues in Wales today. It negatively impacts cattle health, affects profitability and trade, and can decimate years of genetic improvement towards desirable production traits. It also imposes substantial financial, social, and psychological burdens on farming communities. Eradication of bTB requires an understanding of local transmission pathways to target effective disease-control interventions. In this study, we characterised the genomic diversity of M. bovis across Wales by analysing the genome sequence of 379 M. bovis isolates obtained from culture-positive animals in Wales in 2021. Analyses uncovered three prevalent clusters that are geographically distinct. A further three clusters containing fewer isolates were also geographically separated, two of which had particularly large SNP distances from most other Welsh isolates, suggesting independent introductions of M. bovis strains that are not endemic to Wales. Fine-scale and epidemiologically relevant genetic structuring was identified within the six main clusters, indicating region-specific evolution, which can drive local disease dynamics. Finally, SNPs were identified in coding genes that have the potential for important advantageous physiological consequences that may impact host-pathogen interactions and necessitate further investigation.

Animals↗

Synonymous mutations in CFTR exon 12 affect splicing and are not neutral in evolution.

It is well established that exonic sequences contain regulatory elements of splicing that overlap with coding capacity. However, the conflict between ensuring splicing efficiency and preserving the coding capacity for an optimal protein during evolution has not been specifically analyzed. In fact, studies on genomic variability in fields as diverse as clinical genetics and molecular evolution mainly focus on the effect of mutations on protein function. Synonymous variations, in particular, are assumed to be functionally neutral both in clinical diagnosis and when measuring evolutionary distances between species. Using the cystic fibrosis transmembrane conductance regulator (CFTR) exon 12 splicing as a model, we have established that about one quarter of synonymous variations result in exon skipping and, hence, in an inactive CFTR protein. Furthermore, comparative splicing evaluation of mammalian sequence divergences showed that artificial combinations of CFTR exon 12 synonymous and nonsynonymous substitutions are incompatible with normal RNA processing. In particular, the combination of the mouse synonymous with the human missense variations causes exon skipping. It follows that there are two sequential levels at which evolutionary selection of genomic variants take place: splicing control and protein function optimization.

Amino Acid Sequence↗

Recoding: dynamic reprogramming of translation.

A minority of genes in probably all organisms rely on "recoding" for translation of their mRNAs. In these cases, the rules for decoding are temporarily altered through the action of specific signals built into the mRNA sequences. Three classes are described. 1. Frameshifting at a particular site allows expression of a protein from an mRNA with overlapping open reading frames, often giving two protein products from one mRNA. 2. The meanings of code words are altered: specific stop codons can be redirected to encode selenocysteine, tryptophan, or glutamine. 3. Ribosomes can translate over coding gaps in mRNA. These novel mechanisms expand the repertoire of the genetic code and are at the heart of several regulatory schemes.

Animals↗

[Plant resistance genes: molecular and genetic organization, function and evolution].

Remarkable progress is achieved now in comprehension of mechanisms that determine functioning of genes responsible for plants' phytopathogenic resistance (genes R). Cloning of great number of Monocotyledones and Dicotyledones resistance genes show that most of proteins coded by these genes have conserved amino-acid motives, which show high homology to amino-acid motives of proteins with well-designated function. Common structures for most proteins produced by genes R include nucleotide-blinding site (NBS), leucine-rich repeat (LRR), site containing homology with the cytoplasmic domains of the Drosophila Toll protein and the mammalian interleukin-1 receptor (TIR), coiled-coil structure (CC), transmembrane domain (TM), and serine/threonine proteinkinase domain (PK). They are combined within the basic classes of resistance genes proteins as follows: TIR-NBS-LRR, CC-NBS-LLRR, NBS-LRR, PK, TM-CC, LRR-TM, LRR-TM-PK. The domains of proteins produced by plant resistance genes cause specific recognition of avirulence genes products and activate signaling cascade, which gives rise to resistance reaction. Some classes of plant resistance genes probably have the same evolutionary origin as the genes that control the innate immunity of ancient animals. The evolution of plant R genes proceeds primarily by duplication and equal or unequal meiotic recombination. The research on genes R functioning besides its theoretical value is a matter of considerable practical interest for construction of plant genotypes resistant against harmful organisms. The progress in comprehension of mechanisms responsible for specificity of avirulence determinants in phytopathogenic organisms recognition makes possible the creation of artificial resistance genes.

Binding Sites↗

Increased genetic diversity in mitochondrial genes is correlated with the evolution of parasitism in the Hymenoptera.

A higher AT content and rate of mtDNA sequence divergence was found in parasitic wasps (Apocrita) compared with nonparasitic wasps (Symphyta). The compositional bias was reflected in extreme codon bias for a cytochrome oxidase I protein coding gene fragment as well as in the types of amino acid substitutions that have occurred during the evolution of this gene fragment. In some instances, compositional bias influenced the definition of a conservative amino acid change. The increased rate of mtDNA sequence evolution probably arose during the early Jurassic, coincident with the first appearance of parasitic wasps in the fossil record. Our results suggest a causal link between the rate of sequence divergence and the parasitic lifestyle.

Animals↗

Pseudogene evolution and natural selection for a compact genome.

Pseudogenes are nonfunctional copies of protein-coding genes that are presumed to evolve without selective constraints on their coding function. They are of considerable utility in evolutionary genetics because, in the absence of selection, different types of mutations in pseudogenes should have equal probabilities of fixation. This theoretical inference justifies the estimation of patterns of spontaneous mutation from the analysis of patterns of substitutions in pseudogenes. Although it is possible to test whether pseudogene sequences evolve without constraints for their protein-coding function, it is much more difficult to ascertain whether pseudogenes may affect fitness in ways unrelated to their nucleotide sequence. Consider the possibility that a pseudogene affects fitness merely by increasing genome size. If a larger genome is deleterious--for example, because of increased energetic costs associated with genome replication and maintenance--then deletions, which decrease the length of a pseudogene, should be selectively advantageous relative to insertions or nucleotide substitutions. In this article we examine the implications of selection for genome size relative to small (1-400 bp) deletions, in light of empirical evidence pertaining to the size distribution of deletions observed in Drosophila and mammalian pseudogenes. There is a large difference in the deletion spectra between these organisms. We argue that this difference cannot easily be attributed to selection for overall genome size, since the magnitude of selection is unlikely to be strong enough to significantly affect the probability of fixation of small deletions in Drosophila.

Animals↗

Postgenomic chemical ecology: from genetic code to ecological interactions.

Environmental response genes are defined as those encoding proteins involved in interactions external to the organism, including interactions among organisms and between the organism and its abiotic environment. The general characteristics of environmental response genes include high diversity, proliferation by duplication events, rapid rates of evolution, and tissue- or temporal-specific expression. Thus, environmental response genes include those that encode proteins involved in the manufacture, binding, transport, and breakdown of semiochemicals. Postgenomic elucidation of the function of such genes requires an understanding of the chemical ecology of the organism and, in particular, of the "small molecules" that act as selective agents either by promoting survival or causing selective mortality. In this overview, the significance of several groups of environmental response genes is examined in the context of chemical ecology. Cytochrome P-450 monooxygenases provide a case in point; these enzymes are involved in the biosynthesis of furanocoumarins (furocoumarins), toxic allelochemicals, in plants, as well as in their detoxification by lepidopterans. Biochemical innovations in insects and plants have historically been broadly defined in a coevolutionary context. Considerable insight can be gained by defining with greater precision components of those broad traits that contribute to diversification. Molecular approaches now allow chemical ecologists to characterize specifically those biochemical innovations postulated to lead to adaptation and diversification in plant/insect interactions.

Animals↗

41 kilobases of analyzed sequence from the pseudoautosomal and sex-determining regions of the short arm of the human Y chromosome.

Determination of 41.2 kb of Y chromosome genomic sequence has been made from a cosmid that spans the Yp pseudoautosomal boundary and includes 18.5 kb of sequence from the patient-defined sex-determining region of the Y chromosome. An AceDB database of the sequence and the analysis data have been produced as a resource for studies of the evolution and population genetics of the Y chromosome. Comparison of the 18.5 kb from the sex determining region to the sex determining region of mouse does not locate any areas of similarity outside SRY/Sry. Indeed, no coding regions other than those previously reported can be detected anywhere in the 41 kb. The Y-specific and pseudoautosomal portions of this sequence have different repeat sequence and GC contents: this may have relevance both to the events defining the pseudoautosomal boundary and to the course of sequence evolution in the absence of recombination.

Animals↗

Birth of a chimeric primate gene by capture of the transposase gene from a mobile element.

The emergence of new genes and functions is of central importance to the evolution of species. The contribution of various types of duplications to genetic innovation has been extensively investigated. Less understood is the creation of new genes by recycling of coding material from selfish mobile genetic elements. To investigate this process, we reconstructed the evolutionary history of SETMAR, a new primate chimeric gene resulting from fusion of a SET histone methyltransferase gene to the transposase gene of a mobile element. We show that the transposase gene was recruited as part of SETMAR 40-58 million years ago, after the insertion of an Hsmar1 transposon downstream of a preexisting SET gene, followed by the de novo exonization of previously noncoding sequence and the creation of a new intron. The original structure of the fusion gene is conserved in all anthropoid lineages, but only the N-terminal half of the transposase is evolving under strong purifying selection. In vitro assays show that this region contains a DNA-binding domain that has preserved its ancestral binding specificity for a 19-bp motif located within the terminal-inverted repeats of Hsmar1 transposons and their derivatives. The presence of these transposons in the human genome constitutes a potential reservoir of approximately 1,500 perfect or nearly perfect SETMAR-binding sites. Our results not only provide insight into the conditions required for a successful gene fusion, but they also suggest a mechanism by which the circuitry underlying complex regulatory networks may be rapidly established.

Amino Acid Sequence↗