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PubMed1988

Regulation of valine and alpha-ketoisocaproate metabolism in rat kidney mitochondria.

Activities of branched-chain amino acid (BCAA) aminotransferase (BCAT) and alpha-keto acid dehydrogenase (BCKD) were assayed in mitochondria isolated from kidneys of rats. Rates of transamination of valine and oxidation of keto acids alpha-ketoisocaproate (KIC) or alpha-ketoisovalerate (KIV) were estimated using radioactive tracers of the appropriate substrate from amounts of 14C-labeled products formed (14CO2 or [1-14C]-keto acid). Because of the high mitochondrial BCAT activity, an amino acceptor for BCAT, alpha-ketoglutarate (alpha-KG) or KIC, was added to the assay medium when valine was the substrate. Rates of valine transamination and subsequent oxidation of the KIV formed were determined with 0.5 mM alpha-KG as the amino acceptor; these rates were 5- to 50-fold those without added alpha-KG. Rates of CO2 evolution from valine also increased when KIC (0.01-0.10 mM) was present; however, with KIC concentrations above 0.2 mM, rates of CO2 evolution from valine declined although rates of transamination continued to rise. When 0.05 mM KIC was added to the assay medium, oxidation of KIC was suppressed by inclusion of valine or glutamate in the medium. When valine was present KIC was not oxidized preferentially, presumably because it was also serving as an amino acceptor for BCAT. These results indicate that as the supply of amino acceptor, alpha-KG or KIC, is increased in mitochondria not only is the rate of valine transamination stimulated but also the rate of oxidation of the KIV formed from valine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Significance of interspecies matches when evolutionary rate varies.

We develop techniques to estimate the statistical significance of gap-free alignments between two genomic DNA sequences, using human-mouse alignments as an example. The sequences are assumed to be sufficiently similar that some but not all of the neutrally evolving regions (i.e., those under no evolutionary constraint) can be reliably aligned. Our goal is to model the situation in which the neutral rate of evolution, and hence the extent of the aligning intervals, varies across the genome. In some cases, this permits the weaker of two matches to be judged as less likely to have arisen by chance, provided it lies in a genomic interval with a high level of background divergence. We employ a hidden Markov model to capture variations in divergence rates and assign probability values to gap-free alignments using techniques of Dembo and Karlin, which are related to those used for the same purpose by BLAST. Our methods are illustrated in detail using a 1.49 Mb genomic region. Results obtained from the analysis of human chromosome 22 using these techniques are also provided.

Animals↗
PubMed1997

[Primary and secondary structure of 3'--end of the large subunit ribosomal RNA of silkworm Attacus ricini and evolution implications as inferred from the gene sequence].

The DNA sequence of the 3'-end of LSu-rRNA coding region of silkworm Attacus ricini was determined. By comparisons with the corresponding sequence of H. sapiens, X. leavis, H. momus, A. albopictus, D. melanogaster, C. elegants, S. pombe, M. musculus and M. racemosus, we found that the coding sequence we obtained is very conserved. Phylogenetic tree inferred by Neighbor-joining Method showed that the rate of evolution of insects was much faster than vertebrate. In addition, the secondary structure has also worked out it is highly conserved.

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↗
PubMed2025

A General Principle of Neuronal Evolution Reveals a Human-Accelerated Neuron Type Potentially Underlying the High Prevalence of Autism in Humans.

The remarkable ability of a single genome sequence to encode a diverse collection of distinct cell types, including the thousands of cell types found in the mammalian brain, is a key characteristic of multicellular life. While it has been observed that some cell types are far more evolutionarily conserved than others, the factors driving these differences in the evolutionary rate remain unknown. Here, we hypothesized that highly abundant neuronal cell types may be under greater selective constraint than rarer neuronal types, leading to variation in their rates of evolution. To test this, we leveraged recently published cross-species single-nucleus RNA-sequencing datasets from three distinct regions of the mammalian neocortex. We found a strikingly consistent relationship where more abundant neuronal subtypes show greater gene expression conservation between species, which replicated across three independent datasets covering >106 neurons from six species. Based on this principle, we discovered that the most abundant type of neocortical neurons-layer 2/3 intratelencephalic excitatory neurons-has evolved exceptionally quickly in the human lineage compared to other apes. Surprisingly, this accelerated evolution was accompanied by the dramatic down-regulation of autism-associated genes, which was likely driven by polygenic positive selection specific to the human lineage. In summary, we introduce a general principle governing neuronal evolution and suggest that the exceptionally high prevalence of autism in humans may be a direct result of natural selection for lower expression of a suite of genes that conferred a fitness benefit to our ancestors while also rendering an abundant class of neurons more sensitive to perturbation.

Humans↗
PubMedDate not supplied

[Evolution of the DNA structure: direction, mechanism, rate].

On the basis of the analysis of frequencies of occurence of pyrimidines of different length, the degree of clustering of DNA of a hundred species belonging to different taxons has been determined. A tendency towards increase in the index of DNA clustering was revealed in the sequence: bacteria, invertebrates, fishes, amphibians, reptiles, birds, mammals. A mechanism is postulated, according to which an increase in the degree of clustering of DNA in the process of progressive evolution of species may be due to accumulation of mutations, Pyr in equilibrium Pur transversions, resulting in an increase in the degree of asymmetry of the complementary chains of DNA. That this mechanism does exist is proved by a positive correlation between the degree of clustering of DNA and the degree of asymmetry of natural DNA chains. The mean frequency of mutation of vertebrates is about 4,6-10(-8) substitutions per nucleotide per year. Evolution of different groups of organisms may be accompanied with an increase in the rate of evolution of DNA structure. With the help of a special computer program, proceeding from the amino acid sequence of cytochromes c in 40 species belonging to different taxons, the degree of clustering of pyrimidines and the degree of asymmetry of complementary chains of DNA cistrons coding for cytochrome c was determined. A general tendency towards an increase in the mean values of the corresponding parametres of structure was found in the following: bacteria, invertebrates, fishes, amphibians, reptiles, birds and mammals. Thus, it was established that "neutral" amino acid substitutions in cytochromes are based on the selection of mutations leading to accumulation of pyrimidines in sense H-chain of DNA, and purines--in the corresponding mRNA. The frequency of mutation in cytochrome c of chordates is about 5,2-10(-8) of amino acid residues per year. It is assumed that the evolution modification of DNA structure may be due to increase in the disturbance stability of translation.

Amino Acids↗
PubMed1992

[Evolution and ecological changes of animal viruses].

Although the origin of viruses has not yet been clarified, definite differences in evolutionary patterns have been found among RNA. Retro and DNA viruses. These differences are reflected in infectious diseases. RNA viruses, which have RNA in their genome, replicate many times over in cells within a short period of time, destroying the host cells and causing an acute infection. As the error frequency of RNA replicase enzymes is high, the rate of evolution of RNA viruses is very rapid. Retroviruses also contain RNA as their genome, but the genome RNA is reversely transcribed to the DNA in nuclei and then incorporated into the host chromosome to replicate. The error frequency of reverse transcriptase is also high, and therefore mutations easily occur as well. The transcribed DNA is integrated into host DNA in the nucleus, and it remains in the integrated state for human entire life time, causing chronic disease or developing malignant tumors. As DNA viruses except poxviruses replicate inside the cell nucleus and the error frequency of DNA polymerase is low, the speed of mutation and the degree of resulting diversity are lower than those in the case of the RNA virus. DNA viruses tend to stay inside the body for long periods of time and easily become latent. In this paper, I shall discuss 1) the nature of viruses, 2) the origin of viruses, 3) mutation and recombination, 4) diversity of RNA viruses, 5) quickly changing viral diseases, 6) eradicated viral diseases, 7) chronic and malignant diseases, and 8) control of viral diseases.

Biological Evolution↗
PubMed1988

Analysis of higher-primate phylogeny from transversion differences in nuclear and mitochondrial DNA by Lake's methods of evolutionary parsimony and operator metrics.

In the companion paper (Holmquist et al. 1988), we concluded that there is no agreement on either the correct branching order or differential rates of evolution among the higher primates, and we examined in depth why this uncertainty in the evolutionary understanding of our closest living relatives persists. Recently, Lake developed two novel methods, based on group properties of transition and transversion operators, that (a) permit, in principle, objective resolution of problems of the above type and (b) attach a statistical significance level to the conclusions drawn. In the present paper, we develop formulas for using these two methods in tandem and apply them to study transversion differences in (1) nuclear DNA for a 7-kb segment of the psi eta-globin locus and a 3-kb intergenic region between the psi beta- and delta-globin loci and (2) mitochondrial DNA for the 896-bp fragment of Brown et al. Although each of these nucleotide sequence regions has its characteristic tempo and mode of evolution, the nuclear and mitochondrial data together, comprising a total of 10,939 base positions, support a Homo/Pan clade at the 97% confidence level. If we calibrate the divergence point for humans and chimpanzees at 5 Myr, consideration of the transversion branch lengths for the combined nuclear data indicates that the gorilla lineage branched off 600,000-900,000 years prior to that, although the 2 sigma sampling errors do not preclude either a temporal trifurcation for the three species or a considerably more ancient branch point for the gorilla. To resolve the length of this central branch to a relative accuracy of 25% and 30% will require a factor of 16 and nine times more data, respectively--i.e., in excess of 100,000 homologous nucleotides for each of the four primates. For the nuclear genes, heterogeneity in evolutionary rates between different parts of the genome is mostly restricted to the human lineage for these two segments. The lineage leading to chimpanzees has evolved 0.4 (3-kb fragment) to 3.5 (7-kb segment) times as rapidly as the lineage leading to humans, and that leading to the gorilla has evolved approximately one-fifth to one-half as rapidly as that leading to chimpanzees. Thus, even local molecular clocks can "tick" badly. As significant is the fact that virtually contiguous parts of the genome tick at markedly different rates.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Superoxide dismutase: an evolutionary puzzle.

We have obtained the complete amino acid sequence of copper/zinc-containing superoxide dismutase (SOD, superoxide:superoxide oxidoreductase, EC 1.15.1.1) from Drosophila melanogaster. The sequence of this enzyme is also known for man, horse, cow, and the yeast Saccharomyces cerevisiae. The rate of evolution of this enzyme is far from constant. The number of amino acid substitutions per 100 residues per 100 million years is 30.9 when the three mammals are compared to each other, 10.6 when Drosophila is compared to the three mammals, and 5.8 when the yeast is compared to the four animals. The first value represents one of the fastest evolutionary rates for any protein, the second is similar to the globin rate, and the third is similar to some cytochromes and other slowly evolving proteins. Hence, SOD is not an acceptable evolutionary clock. Another peculiarity of this enzyme is that a two-amino-acid deletion must have occurred independently in the lineages going to the cow and to Drosophila. We conclude that using the primary structure of a single gene or protein to time evolutionary events or to reconstruct phylogenetic relationships is potentially fraught with error.

Amino Acid Sequence↗
PubMed1985

Probing fungal mitochondrial evolution with tRNA.

Sequence data are now available for almost the entire complement of mitochondrial rRNAs from five fungi: Schizosaccharomyces pombe, Saccharomyces cerevisiae, Toropulis glabrata, Aspergillus nidulans and Neurospora crassa. Analysis of these data show that the five mitochondria can be related to a common ancestor. The unusually high similarity between some S. pombe mt tRNAs may be due to a process similar to gene conversion. Using the number of differences between tRNA pairs as a measure of the evolutionary rate the yeast-S. pombe branch has paradoxically a high nuclear rate and a low mt rate of evolution as compared with other branches in the phylogenetic tree. Finally the position of mt tRNA genes in S. pombe is abnormally distinct from gene orders in other mitochondria. All of the above factors must be taken into account when describing the relationship between these mitochondria.

Base Sequence↗
PubMed1990

The ecology and evolution of inducible defenses.

Inducible defenses are responses activated through a previous encounter with a consumer or competitor that confer some degree of resistance to subsequent attacks. While the importance of inducible resistance has long been known in host-parasite interactions, it is only recently that its importance has emerged in other natural systems. Although the structural defenses produced by invertebrates to their competitors and predators are by no means the same as an immune response triggered by parasites, these responses all share the properties of (1) specificity, (2) amplification and (3) memory. This review discusses the following ecological consequences and evolutionary causes of inducible defenses: (1) Inducible defenses render historical factors important in biological interactions and can affect the probability of individual survival and growth, as well as affect population dynamics of consumers in some circumstances. (2) Although the benefits of inducible defenses are often balanced by fitness costs, including reduced growth, reproductive output and survivorship, the role of costs and benefits in the evolution of inducible defenses is by no means clear. A more integrated approach would involve a multivariate analysis of the role of natural selection on the inducible characters of interest, their norms of reaction and correlated fitness characters. (3) The disproportionate representation of inducible, morphological defenses among clonal organisms may be due to both a higher rate of origination and enhanced selection to maintain these defenses in clonal taxa. (4) Inducible defenses should be most common when reliable cues are available, attacks by biological agents are unpredictable, and the fitness gains of defenses are balanced by the costs. An integrated approach to studying inducible defenses would thus combine mechanistic estimates of costs, population-level estimates of defense effectiveness, and genetic estimates of correlations between fitness and inducible characters. This will allow us to estimate rates of evolution in these phenotypically plastic threshold characters.

Animals↗
PubMed2024

An Orthogonal T7 Replisome for Continuous Hypermutation and Accelerated Evolution in E. coli.

Systems that perform continuous hypermutation of designated genes without compromising the integrity of the host genome can dramatically accelerate the evolution of new or enhanced protein functions. We describe an orthogonal DNA replication system in E. coli based on the controlled expression of the replisome of bacteriophage T7. The system replicates circular plasmids that enable high transformation efficiencies and seamless integration into standard molecular biology workflows. Engineering of T7 DNA polymerase yielded variant proteins with mutation rates of 1.7 × 10 -5 substitutions per base in vivo - 100,000-fold above the genomic mutation rate. Continuous evolution using the mutagenic T7 replisome was demonstrated by expanding the substrate scope of TEM-1 β-lactamase and increase activity 1,000-fold against clinically relevant monobactam and cephalosporin antibiotics in less than one week.

Journal Article↗
PubMed1999

Cloning and characterisation of the gene encoding mole rat (Spalax ehrenbergi) growth hormone.

In mammals the structure of pituitary GH is generally strongly conserved, reflecting a slow basal rate of molecular evolution. However, on a few occasions the rate has increased - markedly during the evolution of primates and artiodactyls, and to a small extent during the evolution of rodents and rabbit - giving rise to marked differences between GH sequences of these species. In order to extend knowledge of rodent GHs we have cloned and characterised part of the GH gene of the Eurasian mole rat (Spalax ehrenbergi) using genomic DNA and a PCR technique. The sequence of all of the coding region and 5' untranslated region (UTR), most of the 3' UTR and part of the promoter region is described. The overall organisation of the mole rat GH gene is similar to that of GH genes from other mammals. The proximal Pit-1 sequence in the gene promoter differs somewhat from that of rat or mouse. The deduced sequence for the mature GH from mole rat differs from that of pig GH (thought to be identical to the ancestral placental mammal GH sequence) at 7 residues and from rat, mouse and hamster GHs at 9 to 12 residues. Only one or two of these substitutions involve residues close to the receptor-binding sites of the hormone.

Amino Acid Sequence↗
PubMed1997

[Ultrasonography of acute osteomyelitis of the long bones in children. Diagnostic and prognostic value].

Between 1991 and 1994, ultrasonography was used to investigate 90 consecutive children with acute osteomyelitis. Ultrasonographic findings were analyzed taking into account the time elapsed from first symptoms. Outcome in 47 children who were treated and followed for at least 6 months was also studied. Deep soft tissue swelling adjacent to the affected bone was found to be an early but nonspecific sign which persisted all along the course of the disease. Periosteal elevation smaller than 3 mm, secondary to exsudation or septic fluid, confirmed the disease in earliest stage and was the most frequent ultrasonographic sign in first three days of disease. Treated at that stage, total resolution was obtained in 66% of patients and stabilization, in 34% of cases, without any evolution toward chronicity. Acute osteomyelitis with subperiosteal abscess progressed toward stabilization in 66% of cases and toward chronic osteomyelitis in 8% of cases. 32% of subperiosteal abscess were ruptured; in such situation, progression to chronicity was observed in 26% of patients. Since ultrasonography has been used in our institution for the diagnosis of acute osteomyelitis, the rate of evolution to chronicity spectacularly dropped from 63% to 11%. The main advantage of ultrasonography is an earlier detection of subperiosteal collection that indicates surgical drainage without any delay.

Acute Disease↗
PubMed2005

Functional divergence of the circadian clock proteins in prokaryotes.

Cyanobacteria are only prokaryotes known so far to have a circadian system. It may be based either on two (kaiB and kaiC) or three (kaiA, kaiB and kaiC) circadian genes. The homologs of two circadian proteins, KaiB and KaiC, form four major subfamilies (K1-K4) and also occur in some other prokaryotes. Using the likelihood-ratio tests, we studied a rate shift at the functional divergence of the proteins from the different subfamilies. It appears that only two of the subfamilies (K1 and K2) perform circadian functions. We identified in total 92 sites that have significantly different rates of evolution between the clades K1/K2 and K3/K4; 67 sites (15 in KaiB and 52 in KaiC) been evolving significantly slower in K1/K2 than the overall average for the entire sequence. Many critical sites are located in the identified functionally important motifs and regions, e.g. one of the Walker's motif As, DXXG motif, and two KaiA-binding domains of KaiC. There are also 36 sites (approximately 5%) with rate shift between K1 and K2. The rate shift at these sites may be related to the interaction with KaiA. Rate shift analyses have identified residues whose manipulation in the Kai proteins may lead to better understanding of their functions in the two different types of the cyanobacterial circadian system.

Amino Acid Motifs↗
PubMed2003

A populationwide coalescent analysis of Icelandic matrilineal and patrilineal genealogies: evidence for a faster evolutionary rate of mtDNA lineages than Y chromosomes.

Historical inferences from genetic data increasingly depend on assumptions about the genealogical process that shapes the frequencies of alleles over time. Yet little is known about the structure of human genealogies over long periods of time and how they depart from expectations of standard demographic models, such as that attributed to Wright and Fisher. To obtain such information and to examine the recent evolutionary history of mtDNA and Y-chromosome haplotypes in the Icelandic gene pool, we traced the matrilineal and patrilineal ancestry of all 131,060 Icelanders born after 1972 back to two cohorts of ancestors, one born between 1848 and 1892 and the other between 1798 and 1742. This populationwide coalescent analysis of Icelandic genealogies revealed highly positively skewed distributions of descendants to ancestors, with the vast majority of potential ancestors contributing one or no descendants and a minority of ancestors contributing large numbers of descendants. The expansion and loss of matrilines and patrilines has caused considerable fluctuation in the frequencies of mtDNA and Y-chromosome haplotypes, despite a rapid population expansion in Iceland during the past 300 years. Contrary to a widespread assumption, the rate of evolution caused by this lineage-sorting process was markedly faster in matrilines (mtDNA) than in patrilines (Y chromosomes). The primary cause is a 10% shorter matrilineal generation interval. Variance in the number of offspring produced within each generation was not an important differentiating factor. We observed an intergenerational correlation in offspring number and in the length of generation intervals in the matrilineal and patrilineal genealogies, which was stronger in matrilines and thus contributes to their faster evolutionary rate. These findings may have implications for coalescent date estimates based on mtDNA and Y chromosomes.

Alleles↗
PubMed1996

The inheritance of phenotypes: an adaptation to fluctuating environments.

We discuss simple models for the evolution of rates of spontaneous and induced heritable phenotypic variations in a periodically fluctuating environment with a cycle length between two and 100 generations. For the simplest case, the optimal spontaneous transition rate between two states is approximately 1/n (where n is the cycle length). It is also shown that selection for the optimal transition rate under these conditions is surprisingly strong. When n is small, this means that the heritable variations are produced by non-classical inheritance systems, including non-DNA inheritance systems. Thus, it is predicted that in genes controlling adaptation to such environments, non-classical genetic effects are likely to be observed. We argue that the evolution of spontaneous and induced heritable transitions played an important role in the evolution of ontogenies of both unicellular and multicellular organisms. The existence of a machinery for producing induced heritable phenotypic variations introduces a "Lamarckian" factor into evolution.

Adaptation, Physiological↗
PubMed1992

Phylogeny and evolutionary rates of G protein alpha subunit genes.

Rooted phylogenetic trees for a total of 34 genes encoding the stimulatory (s alpha), inhibitory (i alpha), transducin (t alpha), Gx (x alpha), Gz (z alpha), G11 (alpha 11), G12 (alpha 12), G13 (alpha 13), G16 (alpha 16), Gq (q alpha), and other (o alpha) G protein alpha subunits have been constructed. The analysis shows that the G12 (alpha 12 and alpha 13), Gq (alpha 11, alpha 16, and q alpha), and Gs (s alpha genes) groups form one cluster, and the Gx (x alpha and z alpha genes), G(i) (i alpha genes), Gt (t alpha 1 and t alpha 2), and G(o) (o alpha genes) groups form another cluster. During mammalian evolution, the rates of synonymous substitutions for these genes were estimated to be between 1.77 x 10(-9)/site/year and 5.63 x 10(-9)/site/year, whereas those of non-synonymous substitutions were between 0.008 x 10(-9)/site/year and 0.067 x 10(-9)/site/year. These evolutionary rates are similar to those for histone genes, suggesting equally important biological functions of the G protein alpha subunits.

Amino Acid Sequence↗