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PubMed2004

Identification of genes with fast-evolving regions in microbial genomes.

Complete sequences of multiple strains of the same microbial species provide an invaluable source for studying the evolutionary dynamics between orthologous genes over a relatively short time scale. Usually the intensity of the selection pressure is inferred from a comparison between the nonsynonymous substitution rate and the synonymous substitution rate. In this paper, we propose an alternative method for detecting genes with one or more fast-evolving regions from pairwise comparisons of orthologous genes. Our method looks for regions with overrepresented nonsynonymous mutations along the alignment, and requires a higher nonsynonymous evolution rate in those regions than the neutral evolution rate. It identifies gene targets under intensive selection pressure that are not detected from the conventional rate comparison analysis. For those identified genes with known annotations, most of them have a clear role in processes such as bacterial defense and host-pathogen interactions. Gene sets reported from our method provide a measure of the phenotypic divergence between two closely related genomes.

Amino Acid Sequence↗
PubMed1993

How much do we know about spontaneous human mutation rates?

The much larger number of cell divisions between zygote and sperm than between zygote and egg, the increased age of fathers of children with new dominant mutations, and the greater evolution rate of pseudogenes of the Y chromosome than of those on autosomes all point to a much higher mutation rate in human males than in females, as first pointed out by Haldane [Ann Eugen 13:262-271, 1947] in his classical study of X-linked hemophilia. The age of the father is the main factor determining the human spontaneous mutation rate, and probably the total mutation rate. The total mutation rate in Drosophila males of genes causing minor reduction in viability is at least 0.4 per sperm, and may be considerably higher. The great mutation load implied by a rate of approximately 1 per zygote can be greatly ameliorated by quasi-truncation selection. Corresponding data are not available for the human population. The evolution rate of pseudogenes in primates suggests some 10(2) new mutations per zygote. Presumably the overwhelming majority of these are neutral, but even the approximate fraction is not known. Statistical evidence in Drosophila shows that mutations with minor effects cause about the same heterozygous impairment of fitness as those that are lethal when homozygous. The magnitude of heterozygous effect is such that almost all mutant genes are eliminated as heterozygotes before ever becoming homozygous. Although quantitative data in the human species are lacking, anecdotal information supports the conclusion that partial dominance is the rule here as well. This suggests that if the human mutation rate were increased or decreased, the effects would be spread over a period of 50-100 generations.

Age Factors↗
PubMed1998

Association of His117 in the D2 protein of photosystem II with a chlorophyll that affects excitation-energy transfer efficiency to the reaction center.

His117 of the D2 protein of photosystem II (PS II) is a conserved residue in the second transmembrane region of the protein and has been suggested to bind chlorophyll. Nine site-directed mutations were introduced at residue 117, using both photosystem I (PS I)-containing and PS I-less background strains of the cyanobacterium Synechocystis sp. PCC 6803. Of these nine, four (H117C, H117M, H117N, and H117T) were photoautotrophic in the PS I-containing background. The other mutants (H117F, H117L, H117P, H117R, and H117Y) did not accumulate appreciable amounts of PS II in their thylakoids. The type of residues that can functionally replace His117 support the notion of His117 serving as a chlorophyll ligand. The properties of the H117N and H117T mutants were characterized in more detail. Whereas the properties of the H117N mutant were close to those of wild type, in the H117T mutant the 77-K fluorescence emission spectrum shows a much smaller amplitude at 695 nm than expected on the basis of the amount of PS II that is present. Moreover, in H117T, the amount of light needed to half-saturate O2-evolution rates was twofold higher than in the control strain, and the variable fluorescence yield was quenched. However, O2 evolution rates at saturating light intensity and electron-transport kinetics were normal in the mutant. Also, the radical accessory chlorophyll (Chlz+) formed by donation of an electron to the PS-II reaction center could be generated normally by illumination at low temperature in the H117T mutant. We conclude that the chlorophyll associated with residue 117 of the D2 protein is important for efficient excitation transfer between the proximal antenna and the PS II reaction center. A possible mechanism involving a chlorophyll cation to explain the quenching in the H117T mutant is discussed.

Chlorophyll↗
PubMed1999

Conversion of furfural in aerobic and anaerobic batch fermentation of glucose by Saccharomyces cerevisiae.

The effect of furfural on aerobic and anaerobic batch cultures of Saccharomyces cerevisiae CBS 8066 growing on glucose was investigated. Furfural was found to decrease both the specific growth rate and ethanol production rate after pulse additions in both anaerobic and aerobic batch cultures. The specific growth rate remained low until the furfural had been completely consumed, and then increased somewhat, but not to the initial value. The CO(2) evolution rate decreased to about 35% of the value before the addition of 4 g x l(-1) furfural, in both aerobic and anaerobic fermentations. The decrease of the CO(2) evolution rate was rapid at first, and then a more gradual decrease was observed. The furfural was converted mainly to furfuryl alcohol, with a specific conversion rate of 0.6 (+/-0.03) g (furfural) x g(-1) (biomass) x h(-1) by exponentially growing cells. However, the conversion rate of furfural by cells in the stationary phase was much lower. A previously unidentified compound was detected during the conversion of furfural. This compound was characterized by mass spectrometry and it is suggested that it is formed from furfural and pyruvate.

Journal Article↗
PubMed1987

Basic studies of hydrogen evolution by Escherichia coli containing a cloned Citrobacter freundii hydrogenase gene.

Citrobacter freundii genes that complemented Escherichia coli hyd-(hydrogenase activity) mutation were cloned in plasmids pCBH4 (6.2 kb) and pCBH6(5.7 kb). Hydrogen evolution by the transformant E. coli HK-8(pCBH4 or pCBH6) was investigated. The optimum culture temperature of recombinant E. coli cells for hydrogen evolution from glucose was in the neighborhood of 18 degrees C. The recombinant E. coli cells cultured at this condition showed a several-fold increase of hydrogen evolution, as compared with that of the wild-type cells. The plasmid-retention stability of this recombinant E. coli was extremely high, especially plasmid pCBH4, which was completely retained during 2 wk without any restriction. Hydrogen production by immobilized recombinant E. coli was then investigated using cells cultured at 18 degrees C. The hydrogen evolution rate from glucose and Lennox-broth were about twofold higher than that of E. coli C600, and this high hydrogen evolution rate was maintained for more than 1 mo.

Citrobacter↗
PubMed1994

The Effects of Excess Irradiance on Photosynthesis in the Marine Diatom Phaeodactylum tricornutum.

The response of Phaeodactylum tricornutum to excess light was remarkably similar to that observed in higher plants and green algae and was characterized by complex changes in minimal fluorescence yields of fully dark-adapted samples and declines in maximum variable fluorescence levels and oxygen evolution rates. In our study the parallel decreases in the effective rate constant for photosystem II (PSII) photochemistry, the variable fluorescence yield of a dark-adapted sample, and light-limited O2 evolution rates after short (0-10 min) exposures to photoinhibitory conditions could not be attributed to damage or down-regulation of PSII reaction centers. Instead, these changes were consistent with the presence of nonphotochemical quenching of PSII excitation energy in the antennae. This quenching was analogous to that component of nonphotochemical quenching studied in higher plants that is associated with photoinhibition of photosynthesis and/or processes protecting against photoinhibition in that it did not relax readily in the dark and persisted in the absence of a bulk transthylakoid proton gradient. The quenching was most likely associated with photoprotective processes in the PSII antenna that reduced the extent of photoinhibitory damage, particularly after longer exposures. Our results suggest that a large population of damaged, slowly recovering PSII centers did not form in Phaeodactylum even after 60 min of exposure to excess actinic light.

Journal Article↗
PubMed1991

The rate of Cu,Zn superoxide dismutase evolution.

The rate of amino acid replacement in Cu,Zn SOD greatly departs from the expectations of the molecular clock. We examine 27 Cu,Zn SOD sequences available and conclude that: (1) the SOD enzymes from different mammal families differ from each other by roughly the same number of replacements, which is consistent with a simultaneous mammalian radiation; (2) over the most recent 60 million years (MY) the rate of SOD evolution is fairly high (15 aa/100 aa/100 MYR) and may be considered constant; (3) the rate of accumulation of amino acid replacements since the divergence of fungi, plants and animals to the present is inconstant along different branches of the evolutionary tree; moreover it steadily decreases with time, to the same extent in all lineages; (4) some comparisons exhibit divergences that are in any case greater than expected from a Poisson process on the assumption of a molecular clock; (5) plant chloroplast enzymes display fewer differences from each other than cytoplasmic ones; (6) bacteriocuprein (from Photobacterium leiognathi), fluke and human extracellular SOD are all three extremely remotely related to one another and to the SOD of other eukaryotes. The process of consistent decline of the rate of evolution of Cu, Zn SOD can be described by a number of mathematical functions. We explore simple models that assume constant rates and might be applicable to other proteins or genes that apparently evolve at disparate rates.

Amino Acid Sequence↗
PubMed1996

Positive selection and rates of evolution in immunodeficiency viruses from humans and chimpanzees.

Evolutionary theory predicts the recent spread of primate immunodeficiency viruses (PIVs) to new human populations to be accompanied by positive selection in response to new host environments and/or by random genetic drift. I assess evidence for positive selection in human and chimpanzee PIVs type I (PIV1s), using ratios of synonymous to nonsynonymous nucleotide change based on branch lengths and outgroup rooting. Ratios are smaller for PIV1s from humans than for PIV1 from a chimpanzee for the pol, gag, and env glycoprotein 120 (gp120) regions, indicating greater effects of positive selection in PIV1s from humans. Parsimony-based relative rate tests for amino acid changes showed significant differences between PIV1s from humans and chimpanzees in 18 of 48 pairwise comparisons, with all 18 showing faster rates of change in PIV1s from humans. This study indicates that in some instances, the recent evolution of human PIV1s follows a speciational pattern, in which increased diversification of taxa is correlated with greater amounts of character change appearing and being maintained through time. This extends the generality of the speciational pattern to a group of organisms (viruses) having the fastest known rates of anagenetic change for nucleotide characters and indicates that comprehensive understanding of PIV1 evolution requires consideration of both anagenetic change within viral lineages and the relative historical success of different viral clades. Phylogenetic analyses show that neither PIV1s infecting humans nor those infecting chimpanzees represent monophyletic groups and suggest multiple host-species shifts for PIV1s.

Animals↗
PubMed1984

Scoliosis and trunk muscles.

This study examines the role of muscular deficiencies in the origin and development of paralytic scoliosis. We studied spine films of 108 scoliotic curves of poliomyelitic children and results of muscle tests made during the growth phase. We investigated the relationship between spinal and abdominal muscle test values, determined 2 years after the child had experienced the acute phase of anterior polioimyelitis, and the convexity, evolution rate, effects of gravity, and reducibility of the scoliotic deformity. Although paralysis certainly is responsible for triggering scoliosis, it plays no role in determining convexity for thoracic and lumbar patterns, and has little bearing on thoracolumbar curves. It is not at all correlated with the evolution rate, reducibility, or degree of collapse with gravity. The general laws governing the evolution of scoliosis, whatever its origin, are outlined, and several possible pathogenic factors are suggested.

Acute Disease↗
PubMedDate not supplied

Genomic rearrangements in trypanosomatids: an alternative to the "one gene" evolutionary hypotheses?

Most molecular trees of trypanosomatids are based on point mutations within DNA sequences. In contrast, there are very few evolutionary studies considering DNA (re) arrangement as genetic characters. Waiting for the completion of the various parasite genome projects, first information may already be obtained from chromosome size-polymorphism, using the appropriate algorithms for data processing. Three illustrative models are presented here. First, the case of Leishmania (Viannia) braziliensis/L. (V.) peruviana is described. Thanks to a fast evolution rate (due essentially to amplification/deletion of tandemly repeated genes), molecular karyotyping seems particularly appropriate for studying recent evolutionary divergence, including eco-geographical diversification. Secondly, karyotype evolution is considered at the level of whole genus Leishmania. Despite the fast chromosome evolution rate, there is qualitative congruence with MLEE- and RAPD-based evolutionary hypotheses. Significant differences may be observed between major lineages, likely corresponding to major and less frequent rearrangements (fusion/fission, translocation). Thirdly, comparison is made with Trypanosoma cruzi. Again congruence is observed with other hypotheses and major lineages are delineated by significant chromosome rearrangements. The level of karyotype polymorphism within that "species" is similar to the one observed in "genus" Leishmania. The relativity of the species concept among these two groups of parasites is discussed.

Animals↗
PubMed2002

[Conditionally neutral phylogenetic markers of major taxa: a new aspect of the evolution of macromolecules].

The current phase of molecular phylogenetics can be named the 18S rRNA gene era, which is now approaching the end. To date, almost all phyla of metazoans and many taxa of protists are represented in databases of 18S rRNA gene sequences. The elements of the phylogenetic tree of Metazoa inferred from 18S rRNA genes are characterized by unequal validity: some of them seem to be well grounded; others are not adequately supported, and probably will be revised later. The validity of phylogenetic reconstruction is influenced by two main factors: (1) erroneous grouping of long branches that occur because of abnormally high evolution rate; (2) deficit of phylogenetically informative characters. A method for overcoming these difficulties is suggested in addition to known tools: using phylogenetic markers that are stable within individual taxa and evolve by punctuated equilibrium. These markers are least influenced by the convergence caused by a high evolution rate of the entire gene. The nature of these markers of ancient taxa, paradoxical from the perspective of neutral evolution, is discussed, as well as their importance for establishing monophyly of both new large-scale taxonomic groups of invertebrates (Bilateria + Rhombozoa + Orthonectida + Myxozoa + Cnidaria + Placozoa and Echinodermata + Hemichordata) and some major taxa of Nematoda.

Animals↗
PubMed2003

Differential rates of evolution for the ZFY-related zinc finger genes, Zfy, Zfx, and Zfa in the mouse genus Mus.

A comparative study of the last exon of the zinc finger genes Zfx, Zfy, and Zfa from species of mice in the genus Mus was conducted to assess the extent of gene-specific and chromosome-specific effects on the evolutionary patterns among related X-, Y-, and autosomal-linked genes. Phylogenetic analyses of 29 sequences from Zfx, Zfa, and Zfy from 10 taxa were performed to infer relatedness among the zinc finger loci, and codon-based maximum likelihood analyses were conducted to assess evolutionary pattern among genes. Five models of nucleotide sequence evolution were applied and compared using a likelihood ratio test. Estimates of nonsynonymous to synonymous changes (dN/dS) for these genes suggest that amino acid substitutions are occurring at a more rapid rate across the autosomal- and Y-specific lineages compared to the X-specific lineage, with the Y-specific lineage showing the highest rate under certain models. The data suggest the action of gene-specific effects on evolutionary pattern. In particular, Zfa and Zfy genes, both with presumed restricted expression, appear less functionally constrained relative to ubiquitously expressed Zfx. Slightly elevated dN/dS for Zfy genes in comparison to Zfa also suggest Y-specific effects.

Animals↗
PubMed2006

Mutations, mutation rates, and evolution at the hypervariable VNTR loci of Yersinia pestis.

VNTRs are able to discriminate among closely related isolates of recently emerged clonal pathogens, including Yersinia pestis the etiologic agent of plague, because of their great diversity. Diversity is driven largely by mutation but little is known about VNTR mutation rates, factors affecting mutation rates, or the mutational mechanisms. The molecular epidemiological utility of VNTRs will be greatly enhanced when this foundational knowledge is available. Here, we measure mutation rates for 43 VNTR loci in Y. pestis using an in vitro generated population encompassing approximately 96,000 generations. We estimate the combined 43-locus rate and individual rates for 14 loci. A comparison of Y. pestis and Escherichia coli O157:H7 VNTR mutation rates and products revealed a similar relationship between diversity and mutation rate in these two species. Likewise, the relationship between repeat copy number and mutation rate is nearly identical between these species, suggesting a generalized relationship that may be applicable to other species. The single- versus multiple-repeat mutation ratios and the insertion versus deletion mutation ratios were also similar, providing support for a general model for the mutations associated with VNTRs. Finally, we use two small sets of Y. pestis isolates to show how this general model and our estimated mutation rates can be used to compare alternate phylogenies, and to evaluate the significance of genotype matches, near-matches, and mismatches found in empirical comparisons with a reference database.

Animals↗
PubMed2005

Chromosomal rearrangements are associated with higher rates of molecular evolution in mammals.

Evolutionary rates are not uniformly distributed across the genome. Knowledge about the biological causes of this observation is still incomplete, but its exploration has provided valuable insight into the genomical, historical and demographical variables that influence rates of genetic divergence. Recent studies suggest a possible association between chromosomal rearrangements and regions of greater divergence, but evidence is limited and contradictory. Here, we test the hypothesis of a relationship between chromosomal rearrangements and higher rates of molecular evolution by studying the genomic distribution of divergence between 12,000 human-mouse orthologous genes. Our results clearly show that genes located in genomic regions that have been highly rearranged between the two species present higher rates of synonymous (0.7686 vs. 0.7076) and non-synonymous substitution (0.1014 vs. 0.0871), and that synonymous substitution rates are higher in genes close to the breakpoints of individual rearrangements. The many potential causes of such striking are discussed, particularly in the light of speciation models suggesting that chromosomal rearrangements may have contributed to some of the speciation processes along the human and mouse lineages. Still, there are other possible causes and further research is needed to properly explore them.

Animals↗
PubMed1997

Evolution of the human immunodeficiency virus type 1 subtype-specific V3 domain is confined to a sequence space with a fixed distance to the subtype consensus.

Human immunodeficiency virus type 1 (HIV-1) strains can be separated into genetic subtypes based on phylogenetic analysis of the envelope gene. Once it had been shown that population-wide intrasubtype genetic variation of HIV-1 strains increases in the course of the AIDS epidemic, it remained uncertain whether HIV-1 subtypes are phenotypic entities spreading as distinct virus populations. To examine this, we applied Eigen's concepts of sequence geometry and fitness topography to the analysis of intrasubtype evolution of the gp120 V3 domain of HIV-1 subtypes A, B, C, and D in the course of the global AIDS epidemic. We observed that despite the high evolution rate of HIV-1, the nonsynonymous distances to the subtype consensus of sequences obtained early in the epidemic are similar to those obtained more than 10 years later, in contrast to the synonymous distances, which increased steadily over time. For HIV-1 subtype B, we observed that the evolution rate of the individual sequences is independent of their distance from the subtype B consensus, but for the individual sequences most distant from the consensus evolution away from the consensus is constrained. As a result, individual HIV-1 genomes fluctuate within a sequence space with fixed distance to the subtype consensus. Our findings suggest that the evolution of the V3 domain of HIV-1 subtypes A, B, C, and D is confined to an area in sequence space within a fixed distance to the consensus of a respective subtype. This in turn indicates that each HIV-1 subtype is a distinct viral quasispecies that is well adapted to the present environment, able to maintain its identity in the V3 region over time, and unlikely to merge during progression of the AIDS epidemic.

Consensus Sequence↗
PubMed1988

Fluorescence characteristics of photoinhibition and recovery in a sun and a shade species of the red algal genus porphyra.

The effects of light treatment (2000 micromole photons per square meter per second) for varying periods (up to 60 minutes) on chlorophyll fluorescence characteristics and light-limited rates of O(2) evolution were examined in two Porphyra species. Brief light exposures (5-60 seconds) produced a large decrease in variable fluorescence which was not accompained by photoinhibition of light-limited O(2) evolution rates. This rapid decrease in variable fluorescence was suppressed by carbonylcyanide m-chlorophenylhydrazone, indicating that it was related to formation of a proton gradient across the thylakiod membranes. A second phase of fluorescence quenching started after 5 minutes of illumination in the case of the shade species, Porphyra nereocystis Anderson, and after 30 minutes of illumination in the case of the sun species, Porphyra perforata J. Agardh. The rate of fluorescence quenching in the second phase was similar to the rate of photoinhibition of light-limited O(2) evolution in both cases. The dark recovery of variable fluorescence in light-treated plants was also biphasic consisting of a rapid first phase and a slower second phase in both the Porphyra species. Recovery of P. perforata was more complete than that of P. nereocystis over the same recovery period. This greater capacity for recovery could represent a mechanism by which P. perforata is more resistant to photoinhibition than P. nereocystis.

Journal Article↗
PubMed2006

Fast rate of evolution in alternatively spliced coding regions of mammalian genes.

BACKGROUND: At least half of mammalian genes are alternatively spliced. Alternative isoforms are often genome-specific and it has been suggested that alternative splicing is one of the major mechanisms for generating protein diversity in the course of evolution. Another way of looking at alternative splicing is to consider sequence evolution of constitutive and alternative regions of protein-coding genes. Indeed, it turns out that constitutive and alternative regions evolve in different ways. RESULTS: A set of 3029 orthologous pairs of human and mouse alternatively spliced genes was considered. The rate of nonsynonymous substitutions (dN), the rate of synonymous substitutions (dS), and their ratio (omega = dN/dS) appear to be significantly higher in alternatively spliced coding regions compared to constitutive regions. When N-terminal, internal and C-terminal alternatives are analysed separately, C-terminal alternatives appear to make the main contribution to the observed difference. The effects become even more pronounced in a subset of fast evolving genes. CONCLUSION: These results provide evidence of weaker purifying selection and/or stronger positive selection in alternative regions and thus one more confirmation of accelerated evolution in alternative regions. This study corroborates the theory that alternative splicing serves as a testing ground for molecular evolution.

Alternative Splicing↗