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PubMed2004

Molecular evolution in the yeast transcriptional regulation network.

We analyze the structure of the yeast transcriptional regulation network, as revealed by chromatin immunoprecipitation experiments, and characterize the molecular evolution of both its transcriptional regulators and their target (regulated) genes. We test the hypothesis that highly connected genes are more important to the function of gene networks. Three lines of evidence-the rate of molecular evolution of network genes, the rate at which network genes undergo gene duplication, and the effects of synthetic null mutation in network genes-provide no strong support for this hypothesis. In addition, we ask how network genes diverge in their transcriptional regulation after duplication. Both loss (subfunctionalization) and gain (neofunctionalization) of transcription factor binding play a role in this divergence, which is often rapid. On the one hand, gene duplicates experience a net loss in the number of transcription factors binding to them, indicating the importance of losing transcription factor binding sites after gene duplication. On the other hand, the number of transcription factors that bind to highly diverged duplicates is significantly greater than would be expected if loss of binding played the only role in the divergence of duplicate genes.

Binding Sites↗
PubMed2000

Molecular evolution of the avian CHD1 genes on the Z and W sex chromosomes.

Genes shared between the nonrecombining parts of the two types of sex chromosomes offer a potential means to study the molecular evolution of the same gene exposed to different genomic environments. We have analyzed the molecular evolution of the coding sequence of the first pair of genes found to be shared by the avian Z (present in both sexes) and W (female-specific) sex chromosomes, CHD1Z and CHD1W. We show here that these two genes evolve independently but are highly conserved at nucleotide as well as amino acid levels, thus not indicating a female-specific role of the CHD1W gene. From comparisons of sequence data from three avian lineages, the frequency of nonsynonymous substitutions (K(a)) was found to be higher for CHD1W (1.55 per 100 sites) than for CHD1Z (0.81), while the opposite was found for synonymous substitutions (K(s), 13.5 vs. 22.7). We argue that the lower effective population size and the absence of recombination on the W chromosome will generally imply that nonsynonymous substitutions accumulate faster on this chromosome than on the Z chromosome. The same should be true for the Y chromosome relative to the X chromosome in XY systems. Our data are compatible with a male-biased mutation rate, manifested by the faster rate of neutral evolution (synonymous substitutions) on the Z chromosome than on the female-specific W chromosome.

Amino Acid Sequence↗
PubMed2000

Molecular evolution of HCV genotype 2c persistent infection following mother-to-infant transmission.

The molecular evolution of HCV 2c in a case of vertical transmission was studied by comparing the virus quasispecies in the sera from the mother and from the child in a two-year follow-up. The positivity of HCV-RNA since the delivery accounted for an in-utero infection. The Core-E1 genome region (nt 928-1225) was amplified by polymerase chain reaction (PCR) from serum samples collected at delivery and at 3, 9, 18 and 24 months after birth. The RIBA pattern was characterised by isolated anti-c22 positivity in the serum from mother and in sera from the child during the first 9 months. Additional presence of anti-c33 was observed afterwards. Genetic relatedness among isolates and with a mother minor variant serum (Mo1. 13) was found (mean variability ranged between 0.79% and 1.20%). From phylogenetic analysis this variant was identified as the origin of one of the two main lineages that included all isolates from child sera at 9, 18 and 24 months. The variability analysis has shown that high viral heterogeneity is present in the child serum collected at birth (3.16%). In this phase the dn/ds index (1.26%) indicates the presence of strong selective pressures. The development of child specific immune response at 9th month was concurrent with the disappearance of two mutants at positions 11 and 104 of E1. This rare case of in-utero mother-to-infant transmission can be considered as a model to elucidate the HCV quasispecies diversification during the first stage of infection.

Adult↗
PubMed1996

Stereospecificity for the hydrogen transfer and molecular evolution of pyridoxal enzymes.

We here describe the stereochemical aspects of the reactions of pyridoxal 5'-phosphate (PLP)-dependent enzymes, and the relationship between the stereochemistry of the enzyme reaction and molecular evolution of the enzyme. The reactions of PLP-dependent enzymes proceed through the formation of an anionic Schiff base intermediate between the substrate and the coenzyme. Three stereochemical possibilities exist for the formation and cleavage of bonds in the intermediate: the reaction occurs stereospecifically on either the si- or the re-face of the planar intermediate, or alternatively, non-stereospecifically on both faces. The stereospecificities for hydrogen transfer between C-4' of the cofactor and substrate in the transamination catalyzed by various PLP-dependent enzymes have been studied. The stereospecificities reflect the active-site structures of the enzymes, especially the topographical situation of a coenzyme-substrate Schiff base and a catalytic base for the hydrogen transfer. The aminotransferases and other PLP-enzymes catalyzing the transamination as a side-reaction so far studied catalyze only the si-face specific hydrogen transfer. This suggests that these PLP enzymes have similar active-site structures and are evolved divergently from a common ancestral protein. We recently established a new method for the identification of stereospecificity for the hydrogen transfer, and found that D-amino acid aminotransferase and branched chain L-amino acid aminotransferase, which have significant sequence similarity to each other, catalyze the re-face hydrogen transfer on the intermediate. The X-ray crystallographic studies of D-amino acid aminotransferase showed that the relative arrangement of the catalytic base of the enzyme active center to the C4' of the bound cofactor is opposite to that of other aminotransferases catalyzing the si-face hydrogen transfer. The folding of D-amino acid aminotransferase is also different from those of the other aminotransferase so far studied. Therefore, the classifications of the aminotransferases based on their primary structures, three dimensional structures, and stereochemistry of their hydrogen transfer coincide with one another. We also found that PLP-dependent amino acid racemases, the primary structures of which are similar to none of the other PLP-enzymes, catalyze the non-stereospecific hydrogen transfer on both faces of the planar intermediate. Stereospecificities for the hydrogen transfer suggest convergent evolution of the PLP-dependent enzymes. The stereochemical aspects of the enzyme reactions give a clue to the molecular evolution of the enzymes as well as the primary structures and three-dimensional structures of the enzymes.

Amino Acids↗
PubMed2005

Size of the protein-coding genome and rate of molecular evolution.

In diploid populations of size N, there will be 2 Nmu mutations per nucleotide (nt) site (or per locus) per generation (mu stands for mutation rate). If either the population or the coding genome double in size, one expects 4 Nmu mutations. What is important is not the population size per se but the number of genes (coding sites), the two being often interconverted. Here we compared the total physical length of protein-coding genomes (n) with the corresponding absolute rates of synonymous substitution (K(S)), an empirical neutral reference. In the classical occupancy problem and in the coupons collector (CC) problem, n was expressed as the mean rate of change (K(CC)). Despite inherently very low power of the approaches involving averaging of rates, the mode of molecular evolution of the total size phenotype of the coding genome could be evidenced through differences between the genomic estimates of K(CC) [K(CC)=1/(ln n + 0.57721) n] and rate of molecular evolution, K(S). We found that (1) the estimates of n and K(S) are reciprocally correlated across taxa (r=0.812; p<< 0.001); (2) the gamete-cell division hypothesis (Chang et al. Proc Natl Acad Sci USA 91:827-831, 1994) can be confirmed independently in terms of K(CC)/K(S) ratios; (3) the time scale of molecular evolution changes with change in mutation rate, as previously shown by Takahata (Proc Natl Acad Sci USA 87:2419-2423, 1990), Takahata et al. (Genetics 130:925-938, 1992), and Vekemans and Slatkin (Genetics 137:1157-1165, 1994); (4) the generation time and population size (Lynch and Conery, Science 302:1401-1404, 2003) effects left their "signatures" at the level of the size phenotype of the protein-coding genome.

Codon↗
PubMed2002

Contrasting rates of mitochondrial molecular evolution in parasitic Diptera and Hymenoptera.

We investigated the putative association between the parasitic lifestyle and an accelerated rate of mt genetic divergence, compositional bias, and gene rearrangement, employing a range of parasitic and nonparasitic Diptera and Hymenoptera. Sequences were obtained for the cox1, cox2, 16S, 28S genes, the regions between the cox2 and atp8 genes, and between the nad3 and nad5 genes. Relative rate tests indicated generally that the parasitic lifestyle was not associated with an increased rate of genetic divergence in the Diptera but reaffirmed that it was in the Hymenoptera. Similarly, a departure from compositional stationarity was not associated with parasitic Diptera but was in parasitic Hymenoptera. Finally, mitochondrial (mt) gene rearrangements were not observed in any of the dipteran species examined. The results indicate that these genetic phenomena are not accelerated in parasitic Diptera compared with nonparasitic Diptera. A possible explanation for the differences in the rate of mt molecular evolution in parasitic Diptera and Hymenoptera is the extraordinary level of radiation that has occurred within the parasitic Hymenoptera but not in any of the dipteran parasitic lineages. If speciation events in the parasitic Hymenoptera are associated with founder events, a faster rate of molecular evolution is expected. Alternatively, biological differences between endoparasitic Hymenoptera and endoparasitic Diptera may also account for the differences observed in molecular evolution.

Animals↗
PubMed1995

Molecular evolution of viruses: an interim summary.

The origin and molecular evolution of viruses in this issue is dealt with at two levels: (1) tracing the past evolutionary pathways of viruses belonging to RNA virus families, retroviruses, and small and large DNA viruses; (2) tracing current changes in the RNA and DNA viral genomes that lead to the evolution of new virus mutants. In this interim summary, a time scale for the evolutionary processes is given, based on the accumulated published knowledge concerning the postulated origins of life on planet Earth, and the hypothesis that living cells with RNA genomes may have emerged (the "RNA world hypothesis") that then developed into cells with DNA genomes in eukaryotic and prokaryotic cells (1-3). The ideas about the evolution of RNA and DNA viruses from ancient cellular RNA and DNA molecules over a period of 3.5 billion years are discussed. It may be possible that by studying virus genes and molecular processes in virus-infected cells, and their involvement in the shaping of the genomes of bacteria, yeast, plants, insects, mammals, and humans, it will be possible to understand the importance of viruses in past evolution and to predict their possible impact on current and future evolutionary trends in biology.

DNA, Viral↗
PubMed2003

Why do paralogs persist? Molecular evolution of CYCLOIDEA and related floral symmetry genes in Antirrhineae (Veronicaceae).

CYCLOIDEA (CYC) and DICHOTOMA (DICH) are paralogous genes that determine adaxial (dorsal) flower identity in the bilaterally symmetric flowers of Antirrhinum majus (snapdragon). We show here that the duplication leading to the existence of both CYC and DICH in Antirrhinum occurred before the radiation of the Antirrhineae (the tribe to which snapdragon belongs). We find no additional gene duplications within Antirrhineae. Using explicit codon-based models of evolution in a likelihood framework, we show that patterns of molecular evolution after the duplication that gave rise to CYC and DICH are consistent with purifying selection acting at both loci, despite their known functional redundancy in snapdragon. However, for specific gene regions, purifying selection is significantly relaxed across DICH lineages, relative to CYC lineages. In addition, we find evidence for relaxed purifying selection along the lineage leading to snapdragon in one of two putative functional domains of DICH. A model of selection accounting for the persistence of paralogous genes in the absence of diversifying selection is presented. This model takes into account differences in the degree of purifying selection acting at the two loci and is consistent with subfunctionalization models of paralogous gene evolution.

Antirrhinum↗
PubMed2005

Molecular evolution of FLORICAULA/LEAFY orthologs in the Andropogoneae (Poaceae).

Members of the grass family (Poaceae) exhibit a broad range of inflorescence structures and other morphologies, making the grasses an interesting model system for studying the evolution of development. Here we present an analysis of the molecular evolution of FLORICAULA/LEAFY-like genes, which are important developmental regulatory loci known to affect inflorescence development in a wide range of flowering plant species. We have focused on sequences from the Andropogoneae, a tribe within the grass family that includes maize (Zea mays ssp. mays) and Sorghum (Sorghum bicolor). The FLORICAULA/LEAFY gene phylogeny we generated largely agrees with previously published phylogenies for the Andropogoneae using other nuclear genes but is unique in that it includes both members of one of the many duplicate gene sets present in maize. The placement of these sequences in the phylogeny suggests that the duplication of the maize FLORICAULA/LEAFY orthologs, zfl1 and zfl2, is a consequence of a proposed tetraploidy event that occurred in the common ancestor of Zea and a closely related genus, Tripsacum. Our data are consistent with the hypothesis that the transcribed regions of the FLORICAULA/LEAFY-like genes in the Andropogoneae are functionally constrained at both nonsynonymous and synonymous sites and show no evidence of directional selection. We also examined conservation of short noncoding sequences in the first intron, which may play a role in gene regulation. Finally, we investigated the genetic diversity of one of the two maize FLORICAULA/LEAFY orthologs, zfl2, in maize and its wild ancestor, teosinte (Z. mays ssp. parviglumis), and found no evidence for selection pressure resulting from maize domestication within the zfl2-coding region.

Base Sequence↗
PubMed2001

HIV-1 and HIV-2 LTR nucleotide sequences: assessment of the alignment by N-block presentation, "retroviral signatures" of overrepeated oligonucleotides, and a probable important role of scrambled stepwise duplications/deletions in molecular evolution.

Previous analyses of retroviral nucleotide sequences, suggest a so-called "scrambled duplicative stepwise molecular evolution" (many sectors with successive duplications/deletions of short and longer motifs) that could have stemmed from one or several starter tandemly repeated short sequence(s). In the present report, we tested this hypothesis by focusing on the long terminal repeats (LTRs) (and flanking sequences) of 24 human and 3 simian immunodeficiency viruses. By using a calculation strategy applicable to short sequences, we found consensus overrepresented motifs (often containing CTG or CAG) that were congruent with the previously defined "retroviral signature." We also show many local repetition patterns that are significant when compared with simply shuffled sequences. First- and second-order Markov chain analyses demonstrate that a major portion of the overrepresented oligonucleotides can be predicted from the dinucleotide compositions of the sequences, but by no means can biological mechanisms be deduced from these results: some of the listed local repetitions remain significant against dinucleotide-conserving shuffled sequences; together with previous results, this suggests that interspersed and/or local mononucleotide and oligonucleotide repetitions could have biased the dinucleotide compositions of the sequences. We searched for suggestive evolutionary patterns by scrutinizing a reliable multiple alignment of the 27 sequences. A manually constructed alignment based on homology blocks was in good agreement with the polypeptide alignment in the coding sectors and has been exhaustively assessed by using a multiplied alphabet obtained by the promising mathematical strategy called the N-block presentation (taking into account the environment of each nucleotide in a sequence). Sector by sector, we hypothesize many successive duplication/deletion scenarios that fit our previous evolutionary hypotheses. This suggests an important duplication/deletion role for the reverse transcriptase, particularly in inducing stuttering cryptic simplicity patterns.

Algorithms↗
PubMed1997

Molecular evolution and optimization.

Microbial populations (and life) not only evolve, they optimize. The transition from a random, unorganized, lifeless Earth to the present situation, where the Earth is virtually covered with nucleic acids and diverse and complex species, required numerous molecular changes and the integration of metabolic pathways over billions of years. Primitive prokaryotic life was dependent on and constrained by the physical-chemical conditions on the Earth, while slowly reshaping conditions present. In this review, molecular evolution and molecular optimization are examined with an emphasis on the order in which evolutionary events occurred.

Cells↗
PubMed1999

Naturalists, molecular biologists, and the challenges of molecular evolution.

Biologists and historians often present natural histoy and molecular biology as distinct, perhaps conflicting, fields in biological research. Such accounts, although supported by abundant evidence, overlook important areas of overlap between these areas. Focusing upon examples drawn particularly from systematics and molecular evolution, I argue that naturalists and molecular biologists often share questions, methods, and forms of explanation. Acknowledging these interdisciplinary efforts provides a more balanced account of the development of biology during the post-World War II era.

Biological Evolution↗
PubMed2003

Comparative physiology and molecular evolution of carbonic anhydrase in the erythrocytes of early vertebrates.

The different isozymes of carbonic anhydrase (CA) have been the subject of intensive study in mammals, but there is still much to be learned about the early evolution of this enzyme in vertebrates. Erythrocyte CA plays an essential role in the respiratory processes of most vertebrates and is probably the most well studied CA isozyme. The available evidence indicates that there has been a progressive increase in the efficiency of erythrocyte CA during the early evolution of vertebrates. There also appears to be a substantial increase in erythrocyte CA activity during development in some species. At the present time, however, the selective pressures that may be influencing the properties of erythrocyte CA during vertebrate evolution and development have not been clearly determined. When the available molecular sequence information is examined, it is evident that the erythrocyte CAs of early vertebrates have active sites that are more similar to those of mammalian CA VII and II, rather than CA I. We can now also begin to examine the phylogenetic relationships between the different rbc CAs in vertebrates, but more CA sequence information is clearly required from different groups of vertebrates before we have a complete picture of the molecular evolution of erythrocyte CA.

Animals↗
PubMed2003

Detecting adaptive molecular evolution: additional tools for the parasitologist.

It is likely that infectious diseases have shaped the evolution of many vertebrates, including humans. The etiological agents of disease continuously strive to evade the immune response and the immune response, in turn, seeks to change in order to keep pace with the invaders. This 'arms race' may be characterized by the selection for new variant hosts and new variant parasites. Here we discuss the utility of phylogenetics in detecting adaptive evolution at the molecular level and, for illustration, we concentrate on a family of surface-exposed proteins (the rifins) found in the recently sequenced genome of Plasmodium falciparum. We employed phylogeny-based methods in order to characterize adaptive evolution in these proteins. We found evidence for adaptive evolution in many of the amino acid residues in at least one lineage. These results indicate that there has been selection for those strains of P. falciparum that contain the new genotypes. These proteins are likely to be of great importance for the survival of the parasite. Studies of the interaction of these proteins with the antigen-presenting cells of the immune system should lead to a better understanding of malarial infection.

Adaptation, Physiological↗
PubMed2001

PAL: an object-oriented programming library for molecular evolution and phylogenetics.

Phylogenetic Analysis Library (PAL) is a collection of Java classes for use in molecular evolution and phylogenetics. PAL provides a modular environment for the rapid construction of both special-purpose and general analysis programs. PAL version 1.1 consists of 145 public classes or interfaces in 13 packages, including classes for models of character evolution, maximum-likelihood estimation, and the coalescent, with a total of more than 27000 lines of code. The PAL project is set up as a collaborative project to facilitate contributions from other researchers. AVAILIABILTY: The program is free and is available at http://www.pal-project.org. It requires Java 1.1 or later. PAL is licensed under the GNU General Public License.

Computational Biology↗
PubMed2001

Sequence diversity and molecular evolution of the leukotoxin (lktA) gene in bovine and ovine strains of Mannheimia (Pasteurella) haemolytica.

The molecular evolution of the leukotoxin structural gene (lktA) of Mannheimia (Pasteurella) haemolytica was investigated by nucleotide sequence comparison of lktA in 31 bovine and ovine strains representing the various evolutionary lineages and serotypes of the species. Eight major allelic variants (1.4 to 15.7% nucleotide divergence) were identified; these have mosaic structures of varying degrees of complexity reflecting a history of horizontal gene transfer and extensive intragenic recombination. The presence of identical alleles in strains of different genetic backgrounds suggests that assortative (entire gene) recombination has also contributed to strain diversification in M. haemolytica. Five allelic variants occur only in ovine strains and consist of recombinant segments derived from as many as four different sources. Four of these alleles consist of DNA (52.8 to 96.7%) derived from the lktA gene of the two related species Mannheimia glucosida and Pasteurella trehalosi, and four contain recombinant segments derived from an allele that is associated exclusively with bovine or bovine-like serotype A2 strains. The two major lineages of ovine serotype A2 strains possess lktA alleles that have very different evolutionary histories and encode divergent leukotoxins (5.3% amino acid divergence), but both contain segments derived from the bovine allele. Homologous segments of donor and recipient alleles are identical or nearly identical, indicating that the recombination events are relatively recent and probably postdate the domestication of cattle and sheep. Our findings suggest that host switching of bovine strains from cattle to sheep, together with inter- and intraspecies recombinational exchanges, has played an important role in generating leukotoxin diversity in ovine strains. In contrast, there is limited allelic diversity of lktA in bovine strains, suggesting that transmission of strains from sheep to cattle has been less important in leukotoxin evolution.

Alleles↗
PubMed2002

[Molecular evolution of tandem heterochromatic repeats in connection with their function in the genome of Drosophila melanogaster].

Molecular evolution and divergence of paralogous tandem heterochromatic repeats Stellate and Su(Ste) located on the X and Y chromosomes, respectively, are discussed. These repeats appear to emerge as a result of amplification of a unique autosomal euchromatic gene encoding the regulatory beta-subunit of the CK2 protein kinase. The autosomal gene and the clusters of heterochromatic repeats are transcribed in testes. A high level of the Stellate expression leads to partial male sterility and disturbed meiosis. The Stellate expression and its adverse effects are suppressed by homologous Su(Ste) repeats. In genome evolution, the open reading frames (ORF) of Stellate and Su(Ste) putative ancestor were maintained by translational selection. Then the coding Su(Ste) function had been damaged and switched to a new one related to antisense Su(Ste) transcription and suppression of the Stellate genes. Symmetrical (sense and antisense) Su(Ste) transcription causes the formation of a double-strand RNA, which by interference (selective switching off the homologous gene expression) suppresses the Stellate genes. The biological significance and the driving forces of evolution of the species-specific balanced interaction of Stellate and Su(Ste) repeats remain mysterious.

Amino Acid Sequence↗
PubMed2004

[Studies on the nucleotides sequences of extended-spectrum-beta-lactamases encoding genes of Escherichia coli and Klebsiella pneumoniae and the related molecular evolution].

OBJECTIVE: To identify TEM-type and SHV-type ESBLs encoding genes of ESBLs-producing Klebsiella pneumoniae and Escherichia coli isolated from clinical species in West China Hospital of Sichuan University and study the molecular evolution of the ESBLs. METHODS: The nucleotide sequences of TEM-type and SHV-type ESBLs encoding genes amplified by PCR were detected by automatic sequencer, and the subtypes of the encoding genes were determined by Blastx searching. The molecular evolution of ESBLs was studied by means of bioinformatics. RESULTS: In this study, the subtypes of ESBLs were SHV-2 and TEM-19, the distribution of silent mutation in ten bla(SHV-2) was identical, and that of two bla(TEM-19) was the same; the distribution of silent mutation of bla(TEM-19) was the same as that of bla(TEM-1). The distribution of silent mutation of bla(SHV-2) observed here was different from that observed in other countries. CONCLUSION: SHV-2 was the main ESBLs in this study. The bla(SHV-2) and bla(TEM-19) in this study originated from the same transferable variants respectively. The prevalent SHV-2 in different countries resulted from convergent evolution. It seems possible that the bla(TEM-19) identified by this study might originate directly from the transferable bla(TEM-1) identified in this study.

DNA, Bacterial↗