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Biomedical subjects

C G Kurland

Publications and source records attributed to C G Kurland.

At least 19 recordsLinked to original sources
PubMed2006

Genomics and the irreducible nature of eukaryote cells.

Large-scale comparative genomics in harness with proteomics has substantiated fundamental features of eukaryote cellular evolution. The evolutionary trajectory of modern eukaryotes is distinct from that of prokaryotes. Data from many sources give no direct evidence that eukaryotes evolved by genome fusion between archaea and bacteria. Comparative genomics shows that, under certain ecological settings, sequence loss and cellular simplification are common modes of evolution. Subcellular architecture of eukaryote cells is in part a physical-chemical consequence of molecular crowding; subcellular compartmentation with specialized proteomes is required for the efficient functioning of proteins.

Biological Evolution↗
PubMed2003

Horizontal gene transfer: a critical view.

It has been suggested that horizontal gene transfer (HGT) is the "essence of phylogeny." In contrast, much data suggest that this is an exaggeration resulting in part from a reliance on inadequate methods to identify HGT events. In addition, the assumption that HGT is a ubiquitous influence throughout evolution is questionable. Instead, rampant global HGT is likely to have been relevant only to primitive genomes. In modern organisms we suggest that both the range and frequencies of HGT are constrained most often by selective barriers. As a consequence those HGT events that do occur most often have little influence on genome phylogeny. Although HGT does occur with important evolutionary consequences, classical Darwinian lineages seem to be the dominant mode of evolution for modern organisms.

Animals↗
PubMed2002

The global phylogeny of glycolytic enzymes.

Genes encoding the glycolytic enzymes of the facultative endocellular parasite Bartonella henselae have been analyzed phylogenetically within a very large cohort of homologues from bacteria and eukaryotes. We focus on this relative of Rickettsia prowazekii along with homologues from other alpha-proteobacteria to determine whether there have been systematic transfers of glycolytic genes from the presumed alpha-proteobacterial ancestor of the mitochondrion to the nucleus of the early eukaryote. The alpha-proteobacterial homologues representing the eight glycolytic enzymes studied here tend to cluster in well-supported nodes. Nevertheless, not one of these alpha-proteobacterial enzymes is related as a sister clade to the corresponding eukaryotic homologues. Nor is there a close phylogenetic relationship between glycolytic genes from Eucarya and any other bacterial phylum. In contrast, several of the reconstructions suggest that there may have been systematic transfer of sequences encoding glycolytic enzymes from cyanobacteria to some green plants. Otherwise, surprisingly little exchange between the bacterial and eukaryotic domains is observed. The descent of eukaryotic genes encoding enzymes of intermediary metabolism is reevaluated.

Animals↗
PubMed2002

Evolution of microbial genomes: sequence acquisition and loss.

We present models describing the acquisition and deletion of novel sequences in populations of microorganisms. We infer that most novel sequences are neutral. Thus, sequence duplications and gene transfer between organisms sharing the same environment are rarely expected to generate adaptive functions. Two classes of models are considered: (1) a homogeneous population with constant size, and (2) an island model in which the population is subdivided into patches that are in contact through slow migration. Distributions of gene frequencies are derived in a Moran model with overlapping generations. We find that novel, neutral or near-neutral coding sequences in microorganisms will not be fixed globally because they offer large target sizes for mutations and because the populations are so large. At most, such genes may have a transient presence in only a small fraction of the population. Consequently, a microbial population is expected to have a very large diversity of transient neutral gene content. Only sequences that are under strong selection, globally or in individual patches, can be expected to persist. We suggest that genome size is maintained in microorganisms by a quasi-steady state mechanism in which random fluctuations in the effective acquisition and deletion rates result in genome sizes that vary from patch to patch. We assign the genomic identity of a global population to those genes that are required for the participation of patches in the genetic sweeps that maintain the genomic coherence of the population. In contrast, we stress the influence of sequence loss on the isolation and the divergence (speciation) of novel patches from a global population.

Biological Evolution↗
PubMed2000

The dual origin of the yeast mitochondrial proteome.

We propose a scheme for the origin of mitochondria based on phylogenetic reconstructions with more than 400 yeast nuclear genes that encode mitochondrial proteins. Half of the yeast mitochondrial proteins have no discernable bacterial homologues, while one-tenth are unequivocally of alpha-proteobacterial origin. These data suggest that the majority of genes encoding yeast mitochondrial proteins are descendants of two different genomic lineages that have evolved in different modes. First, the ancestral free-living alpha-proteobacterium evolved into an endosymbiont of an anaerobic host. Most of the ancestral bacterial genes were lost, but a small fraction of genes supporting bioenergetic and translational processes were retained and eventually transferred to what became the host nuclear genome. In a second, parallel mode, a larger number of novel mitochondrial genes were recruited from the nuclear genome to complement the remaining genes from the bacterial ancestor. These eukaryotic genes, which are primarily involved in transport and regulatory functions, transformed the endosymbiont into an ATP-exporting organelle.

Alphaproteobacteria↗
PubMed2000

Why mitochondrial genes are most often found in nuclei.

A very small fraction of the proteins required for the propagation and function of mitochondria are coded by their genomes, while nuclear genes code the vast majority. We studied the migration of genes between the two genomes when transfer mechanisms mediate this exchange. We could calculate the influence of differential mutation rates, as well as that of biased transfer rates, on the partitioning of genes between the two genomes. We observe no significant difference in partitioning for haploid and diploid cell populations, but the effective size of cell populations is important. For infinitely large effective populations, higher mutation rates in mitochondria than in nuclear genomes are required to drive mitochondrial genes to the nuclear genome. In the more realistic case of finite populations, gene transfer favoring the nucleus and/or higher mutation rates in the mitochondrion will drive mitochondrial genes to the nucleus. We summarize experimental data that identify a gene transfer process mediated by vacuoles that favors the accumulation of mitochondrial genes in the nuclei of modern cells. Finally, we compare the behavior of mitochondrial genes for which transfer to the nucleus is neutral or influenced by purifying selection.

Cell Nucleus↗
PubMed2000

Growth phase-coupled changes of the ribosome profile in natural isolates and laboratory strains of Escherichia coli.

The growth phase-dependent change in sucrose density gradient centrifugation patterns of ribosomes was analyzed for both laboratory strains of Escherichia coli and natural isolates from the ECOR collection. All of the natural isolates examined formed 100S ribosome dimers in the stationary phase, and ribosome modulation factor (RMF) was associated with the ribosome dimers in the ECOR strains as in the laboratory strain W3110. The ribosome profile (70S monomers versus 100S dimers) follows a defined pattern over time during lengthy culture in both the laboratory strains and natural isolates. There are four discrete stages: (i) formation of 100S dimers in the early stationary phase; (ii) transient decrease in the dimer level; (iii) return of dimers to the maximum level; and (iv) dissociation of 100S dimers into 70S ribosomes, which are quickly degraded into subassemblies. The total time for this cycle of ribosome profile change, however, varied from strain to strain, resulting in apparent differences in the ribosome profiles when observed at a fixed time point. A correlation was noted in all strains between the decay of 100S ribosomes and the subsequent loss of cell viability. Two types of E. coli mutants defective in ribosome dimerization were identified, both of which were unable to survive for a prolonged period in stationary phase. The W3110 mutant, with a disrupted rmf gene, has a defect in ribosome dimerization because of lack of RMF, while strain Q13 is unable to form ribosome dimers due to a ribosomal defect in binding RMF.

Escherichia coli↗
PubMed2000

Origin and evolution of the mitochondrial proteome.

The endosymbiotic theory for the origin of mitochondria requires substantial modification. The three identifiable ancestral sources to the proteome of mitochondria are proteins descended from the ancestral alpha-proteobacteria symbiont, proteins with no homology to bacterial orthologs, and diverse proteins with bacterial affinities not derived from alpha-proteobacteria. Random mutations in the form of deletions large and small seem to have eliminated nonessential genes from the endosymbiont-mitochondrial genome lineages. This process, together with the transfer of genes from the endosymbiont-mitochondrial genome to nuclei, has led to a marked reduction in the size of mitochondrial genomes. All proteins of bacterial descent that are encoded by nuclear genes were probably transferred by the same mechanism, involving the disintegration of mitochondria or bacteria by the intracellular membranous vacuoles of cells to release nucleic acid fragments that transform the nuclear genome. This ongoing process has intermittently introduced bacterial genes to nuclear genomes. The genomes of the last common ancestor of all organisms, in particular of mitochondria, encoded cytochrome oxidase homologues. There are no phylogenetic indications either in the mitochondrial proteome or in the nuclear genomes that the initial or subsequent function of the ancestor to the mitochondria was anaerobic. In contrast, there are indications that relatively advanced eukaryotes adapted to anaerobiosis by dismantling their mitochondria and refitting them as hydrogenosomes. Accordingly, a continuous history of aerobic respiration seems to have been the fate of most mitochondrial lineages. The initial phases of this history may have involved aerobic respiration by the symbiont functioning as a scavenger of toxic oxygen. The transition to mitochondria capable of active ATP export to the host cell seems to have required recruitment of eukaryotic ATP transport proteins from the nucleus. The identity of the ancestral host of the alpha-proteobacterial endosymbiont is unclear, but there is no indication that it was an autotroph. There are no indications of a specific alpha-proteobacterial origin to genes for glycolysis. In the absence of data to the contrary, it is assumed that the ancestral host cell was a heterotroph.

Alphaproteobacteria↗
PubMed1999

Origins of mitochondria and hydrogenosomes.

Complete genome sequences for many mitochondria, as well as for some bacteria, together with the nuclear genome sequence of yeast have provided a coherent view of the origin of mitochondria. In particular, conventional phylogenetic reconstructions with genes coding for proteins active in energy metabolism and translation have confirmed the simplest version of the endosymbiosis hypothesis. In contrast, the hydrogen and the syntrophy hypotheses for the origin of mitochondria do not receive support from the available data. It remains to be seen how the evolution of hydrogenosomes is related to that of mitochondria.

Evolution, Molecular↗
PubMed1999

Molecular phylogeny and rearrangement of rRNA genes in Rickettsia species.

It has previously been observed that Rickettsia prowazekii has an unusual arrangement of the rRNA genes. In this species, the three rRNA genes, 16S (rrs), 23S (rrl), and 5S (rrf), are not linked in the typical arrangements for bacteria. Rather, the 16S rRNA gene has been separated from the 23S and 5S rRNA gene cluster, and the 23S rRNA gene is preceded by a gene which codes for methionyl-tRNAf(Met) formyltransferase (fmt). In this study, we screened the genus Rickettsia for the fmt-rrl motif in order to examine the phylogenetic depth of this unusual rRNA gene organization. A rearranged operon structure was observed in Rickettsia conorii, Rickettsia parkeri, Rickettsia sibirica, Rickettsia rickettsii, Rickettsia amblyomii, Rickettsia montana, Rickettsia rhipicephali, Rickettsia australis, Rickettsia akari, Rickettsia felis, Rickettsia canada, and Rickettsia typhi. There is also evidence for a divided operon in Rickettsia belli, but in this species, the fmt gene could not be identified upstream of the 23S rRNA gene. In order to place the rearrangement event in the evolutionary history of the Rickettsia, phylogenetic analyses were performed based on the fmt-rrl spacer regions and the 23S rRNA genes. Based on these phylogenies, we suggest that the genomic rearrangement of the rRNA genes preceded the divergence of the typhus group and the spotted fever group Rickettsia. The unique organization of the 23S rRNA genes provides a simple diagnostic tool for identification of Rickettsia species.

Base Sequence↗
PubMed1998

The genome sequence of Rickettsia prowazekii and the origin of mitochondria.

We describe here the complete genome sequence (1,111,523 base pairs) of the obligate intracellular parasite Rickettsia prowazekii, the causative agent of epidemic typhus. This genome contains 834 protein-coding genes. The functional profiles of these genes show similarities to those of mitochondrial genes: no genes required for anaerobic glycolysis are found in either R. prowazekii or mitochondrial genomes, but a complete set of genes encoding components of the tricarboxylic acid cycle and the respiratory-chain complex is found in R. prowazekii. In effect, ATP production in Rickettsia is the same as that in mitochondria. Many genes involved in the biosynthesis and regulation of biosynthesis of amino acids and nucleosides in free-living bacteria are absent from R. prowazekii and mitochondria. Such genes seem to have been replaced by homologues in the nuclear (host) genome. The R. prowazekii genome contains the highest proportion of non-coding DNA (24%) detected so far in a microbial genome. Such non-coding sequences may be degraded remnants of 'neutralized' genes that await elimination from the genome. Phylogenetic analyses indicate that R. prowazekii is more closely related to mitochondria than is any other microbe studied so far.

DNA Replication↗
PubMed1998

A phylogenetic analysis of the cytochrome b and cytochrome c oxidase I genes supports an origin of mitochondria from within the Rickettsiaceae.

We have cloned and sequenced the genes encoding cytochrome b (cob) and cytochrome c oxidase subunit I (cox1) from Rickettsia prowazekii, a member of the alpha-proteobacteria. The phylogenetic analysis supports the hypothesis that mitochondria are derived from the alpha-proteobacteria and more specifically from within the Rickettsiaceae. We have estimated that the common ancestor of mitochondria and Rickettsiaceae dates back to more than 1500 million years ago.

Amino Acids↗
PubMed1998

Reductive evolution of resident genomes.

Small, asexual populations are expected to accumulate deleterious substitutions and deletions in an irreversible manner, which in the long-term will lead to mutational meltdown and genome decay. Here, we discuss the influence of such reductive processes on the evolution of genomes that replicate within the domain of a host genome.

Animals↗
PubMed1998

Evolutionary rates for tuf genes in endosymbionts of aphids.

The gene encoding elongation factor Tu (tuf) in aphid endosymbionts (genus Buchnera) evolves at rates of 1.3 x 10(-10) to 2.5 x 10(-10) nonsynonymous substitutions and 3.9 x 10(-9) to 8.0 x 10(-9) synonymous substitutions per position per year. These rates, which are at present among the most reliable substitution rates for protein-coding genes of bacteria, have been obtained by calibrating the nodes in the phylogenetic tree produced from the Buchnera EF-Tu sequences using divergence times for the corresponding ancestral aphid hosts. We also present data suggesting that the rates of nonsynonymous substitutions are significantly higher in the endosymbiont lineages than in the closely related free-living bacteria Escherichia coli and Salmonella typhimurium. Synonymous substitution rates for Buchnera approximate estimated mutation rates for E. coli and S. typhimurium, as expected if synonymous changes act as neutral mutations in Buchnera. We relate the observed differences in substitution frequencies to the absence of selective codon preferences in Buchnera and to the influence of Muller's ratchet on small asexual populations.

Amino Acid Sequence↗
PubMed1997

Growth rate-optimised tRNA abundance and codon usage.

The abundance of different tRNAs in Escherichia coli at different growth rates correlates strongly with the usage of the corresponding cognate codons. On the assumption that the investment in the translation system is optimised to provide a maximal growth rate, the relationship between tRNA levels and codon usage can be predicted. When the complications due to different degeneracies and different association rate constants for the different tRNA-codon combinations are accounted for, recent data from the literature indicate that the predicted relations hold up very well: the tRNA levels correlate with codon frequencies in a way that would support a maximal growth rate. The relations can also be used to predict the association rate constant between an A-site codon and the cognate ternary complex. In the cases where they can be compared, the results agree reasonably well with experimental results from the literature.

Cell Division↗