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PubMed1998

Evolution of the cytochrome P450 superfamily: sequence alignments and pharmacogenetics.

The evolution of the cytochrome P450 (CYP) superfamily is described, with particular reference to major events in the development of biological forms during geological time. It is noted that the currently accepted timescale for the elaboration of the P450 phylogenetic tree exhibits close parallels with the evolution of terrestrial biota. Indeed, the present human P450 complement of xenobiotic-metabolizing enzymes may have originated from coevolutionary 'warfare' between plants and animals during the Devonian period about 400 million years ago. A number of key correspondences between the evolution of P450 system and the course of biological development over time, point to a mechanistic molecular biology of evolution which is consistent with a steady increase in atmospheric oxygenation beginning over 2000 million years ago, whereas dietary changes during more recent geological time may provide one possible explanation for certain species differences in metabolism. Alignment between P450 protein sequences within the same family or subfamily, together with across-family comparisons, aid the rationalization of drug metabolism specificities for different P450 isoforms, and can assist in an understanding of genetic polymorphisms in P450-mediated oxidations at the molecular level. Moreover, the variation in P450 regulatory mechanisms and inducibilities between different mammalian species are likely to have important implications for current procedures of chemical safety evaluation, which rely on pure genetic strains of laboratory bred rodents for the testing of compounds destined for human exposure.

Amino Acid Sequence↗

PubMed2004

African Haplogroup L mtDNA sequences show violations of clock-like evolution.

A set of 96 complete mtDNA sequences that belong to the three major African haplogroups (L1, L2, and L3) was analyzed to determine if mtDNA has evolved as a molecular clock. Likelihood ratio tests (LRTs) were carried out with each of the haplogroups and with combined haplogroup sequence sets. Evolution has not been clock-like, neither for the coding region nor for the control region, in combined sets of African haplogroup L mtDNA sequences. In tests of individual haplogroups, L2 mtDNAs showed violations of a molecular clock under all conditions and in both the control and coding regions. In contrast, haplogroup L1 and L3 sequences, both for the coding and control regions, show clock-like evolution. In clock tests of individual L2 subclades, the L2a sequences showed a marked violation of clock-like evolution within the coding region. In addition, the L2a and L2c branch lengths of both the coding and control regions were shorter relative to those of the L2b and L2d sequences, a result that indicates lower levels of sequence divergence. Reduced median network analyses of the L2a sequences indicated the occurrence of marked homoplasy at multiple sites in the control region. After exclusion of the L2a and L2c sequences, African mtDNA coding region evolution has not significantly departed from a molecular clock, despite the results of neutrality tests that indicate the mitochondrial coding region has evolved under nonneutral conditions. In contrast, control region evolution is clock-like only at the haplogroup level, and it thus appears to have evolved essentially independently from the coding region. The results of the clock tests, the network analyses, and the branch length comparisons all caution against the use of simple mtDNA clocks.

Black or African American↗

PubMed1978

Instability of plasmid DNA sequences: macro and micro evolution of the antibiotic resistance plasmid R6-5.

Detailed examination of the structure of cloned DNA fragments of the R6-5 antibiotic resistance plasmid has revealed a substantial degree of polynucleotide sequence heterogeneity and indicates that sequence rearrangements in plasmids and possible other replicons occur more frequently than has hitherto been appreciated. The sequences changes in cloned R6-5 fragments were shown in some instances to have occurred prior to cloning, i.e. existing in the original population of R6-5 molecules that was obtained from a single bacterial clone and by several different criteria judged to be homogeneous, and in others to have occurred either during the cloning procedure or during subsequent propagation of hybrid molecules. The molecular changes that are described involved insertion/deletion of the previously characterized IS2 insertion element, formation of a new inverted repeat structure probably by duplication of a preexisting R6-5 DNA sequence, sequence inversion, and loss and gain of restriction endonuclease cleavage sites.

Anti-Bacterial Agents↗

PubMed2004

Rapid genome evolution revealed by comparative sequence analysis of orthologous regions from four triticeae genomes.

Bread wheat (Triticum aestivum) is an allohexaploid species, consisting of three subgenomes (A, B, and D). To study the molecular evolution of these closely related genomes, we compared the sequence of a 307-kb physical contig covering the high molecular weight (HMW)-glutenin locus from the A genome of durum wheat (Triticum turgidum, AABB) with the orthologous regions from the B genome of the same wheat and the D genome of the diploid wheat Aegilops tauschii (Anderson et al., 2003; Kong et al., 2004). Although gene colinearity appears to be retained, four out of six genes including the two paralogous HMW-glutenin genes are disrupted in the orthologous region of the A genome. Mechanisms involved in gene disruption in the A genome include retroelement insertions, sequence deletions, and mutations causing in-frame stop codons in the coding sequences. Comparative sequence analysis also revealed that sequences in the colinear intergenic regions of these different genomes were generally not conserved. The rapid genome evolution in these regions is attributable mainly to the large number of retrotransposon insertions that occurred after the divergence of the three wheat genomes. Our comparative studies indicate that the B genome diverged prior to the separation of the A and D genomes. Furthermore, sequence comparison of two distinct types of allelic variations at the HMW-glutenin loci in the A genomes of different hexaploid wheat cultivars with the A genome locus of durum wheat indicates that hexaploid wheat may have more than one tetraploid ancestor.

Amino Acid Sequence↗

PubMed1976

Sequences of 5S ribosomal RNA from Xenopus mulleri and the evolution of 5S gene-coding sequences.

Sequences for 5S RNA from somatic cells and oocytes of Xenopus mulleri are presented. Comparison with sequences previously given for Xenopus laevis indicates that the somatic 5S RNA genes of each species are more closely related to each other than either is to its own set of oocyte genes, suggesting that somatic and oocyte genes within each species are evolving independently. However, detailed analysis of sequence variants in each species suggests that there is a mechanism which allows occasional genetic exchanges between somatic and oocyte-specific genes. Possible genetic mechanisms which allows such an exchange are discussed.

Animals↗

PubMed1985

The prokaryote-eukaryote interface.

Over the past 30 years the study of the sequences of proteins and nucleic acids has produced almost incredible amounts of information, new concepts, and new avenues of research. The beginning was slow: the first peptide hormones sequenced in the early 1950's, the first cytochrome c (horse) in 1961, the first bacterial ferredoxin in 1964, and the first transfer RNA (yeast alanine tRNA) in 1965. In the past 6 years, the rate of data accumulation has accelerated tremendously, primarily due to technological advances in nucleic acid sequencing techniques. For investigators of biological evolution, the sequence data and the new information on genetic mechanisms would prove to be the best evidence for elucidating relationships among the genomes of living organisms and for deducing phylogenetic history. In particular, they needed evidence to decide between the two hypotheses for the origin of eukaryotic cells. Now, less than 20 years since Margulis renewed the investigation of this problem, comparisons of protein and nucleic acid sequences, especially of the small subunit ribosomal RNAs, have answered this question in favor of the endosymbiotic origin of eukaryotic cells. After briefly discussing some of the concepts that helped resolve this controversy and the problems involved in using sequence data for evolutionary studies, we describe a few examples of useful evolutionary trees.

Amino Acid Sequence↗

PubMed1989

Sequence, organization, transcription and evolution of RNA polymerase subunit genes from the archaebacterial extreme halophiles Halobacterium halobium and Halococcus morrhuae.

The genes for the four largest subunits, A, B', B" and C, of the DNA-dependent RNA polymerase were cloned from the extreme halophile Halobacterium halobium and sequenced and their transcription was analyzed. The downstream half of this gene cluster from another extreme halophile Halococcus morrhuae was also cloned, sequenced and its transcription products characterized. The H. halobium genes were transcribed into a common transcript from an upstream promoter in the order B", B', A and C. They are flanked by, and co-transcribed with, two smaller genes coding for 75 and 139 amino acid residues, respectively. Immediately downstream from these genes were two open reading frames that are homologous to ribosomal proteins S12 and S7 from Escherichia coli. In both extreme halophiles these genes were transcribed from their own promoter, but in Hc. morrhuae there was also considerable read-through from the RNA polymerase genes. Sequence alignment studies showed that the combined B" + B' subunits are equivalent to the B subunits of the eukaryotic polymerases I and II and to the eubacterial beta subunit, while the combined A + C subunits correspond to the A subunits of eukaryotic RNA polymerases I, II and III and to the eubacterial beta' subunit. The sequence similarity to the eukaryotic subunits was always much higher than to the eubacterial subunits. Conserved sequence regions within the individual subunits were located which are likely to constitute functionally important domains; they include sites associated with rifampicin and alpha-amanitin binding and two possible zinc binding fingers. Phylogenetic analyses based on sequence alignments confirmed that the extreme halophiles belong to the archaebacterial kingdom.

Archaea↗

PubMed1991

Genomic organization of adrenergic and serotonin receptors in the mouse: linkage mapping of sequence-related genes provides a method for examining mammalian chromosome evolution.

Five sequence-related genes encoding four adrenergic receptors and a serotonin receptor were localized to specific regions of four mouse chromosomes with respect to 11 other genetic markers. Linkage was established by the analysis of the haplotypes of 114 interspecific backcross mice. Adra2r (alpha 2-C10) and Adrb1r (beta 1) receptors mapped to the distal region of mouse chromosome 19. These genes were separated by 2.6 +/- 1.5 cM in a segment of mouse chromosome 19 that has a similar organization of these genes on the long arm of human chromosome 10. The Adra1r (alpha 1B), Adrb2r (beta 2), and Htra1 (5HT1A) genes mapped to proximal mouse chromosome 11, proximal mouse chromosome 18, and distal mouse chromosome 13, respectively. The organization of genes linked to these loci on regions of the three mouse chromosomes is consistent with the organization of homologous human genes on human chromosome 5. These findings further define the relationship of linkage groups conserved during the evolution of the mouse and human genomes. We have identified a region that may have been translocated during evolution and suggest that the human genomic organization of adrenergic receptors more closely resembles that of a putative primordial ancestor.

Animals↗

PubMed1996

Origin and evolution of homologous repeated sequences in the mitochondrial DNA control region of shrews.

The complete mitochondrial DNA (mtDNA) control region was amplified and directly sequenced in two species of shrew, Crocidura russula and Sorex araneus (Insectivora, Mammalia). The general organization is similar to that found in other mammals: a central conserved region surrounded by two more variable domains. However, we have found in shrews the simultaneous presence of arrays of tandem repeats in potential locations where repeats tend to occur separately in other mammalian species. These locations correspond to regions which are associated with a possible interruption of the replication processes, either at the end of the three-stranded D-loop structure or toward the end of the heavy-strand replication. In the left domain the repeated sequences (R1 repeats) are 78 bp long, whereas in the right domain the repeats are 12 bp long in C. russula and 14 bp long in S. araneus (R2 repeats). Variation in the copy number of these repeated sequences results in mtDNA control region length differences. Southern blot analysis indicates that level of heteroplasmy (more than one mtDNA form within an individual) differs between species. A comparative study of the R2 repeats in 12 additional species representing three shrew subfamilies provides useful indications for the understanding of the origin and the evolution of these homologous tandemly repeated sequences. An asymmetry in the distribution of variants within the arrays, as well as the constant occurrence of shorter repeated sequences flanking only one side of the R2 arrays, could be related to asymmetry in the replication of each strand of the mtDNA molecule. The pattern of sequence and length variation within and between species, together with the capability of the arrays to form stable secondary structures, suggests that the dominant mechanism involved in the evolution of these arrays in unidirectional replication slippage.

Animals↗

PubMed2004

Evolution of an arbitrary sequence in solubility.

We have investigated the evolvability of an insoluble random polypeptide, RP3-34, to a soluble form through iterative mutation and selection with the aid of the green fluorescent protein (GFP) folding reporter. To assess the solubility of the polypeptides in the selected clones of each generation, the polypeptide genes were detached from the GFP fusions and expressed with a His(6) tag. The solubility of the variant random polypeptides increased in each generation within the scope of the evolutionary process, and the polypeptides assumed a soluble form from the fourth generation. Analysis of the synonymous and nonsynonymous mutations found in the deduced amino acid sequence of the selected polypeptides revealed that selection had accelerated the evolutionary rate. The solubility and hydrophobicity of the polypeptides and the 25 arbitrarily chosen random polypeptides found in a previously prepared library were determined, analyzed, and interpreted from the landscape on the protein sequence space. This study showed the evolvability of an insoluble arbitrary sequence toward a soluble one, hence, it provides a new perspective on the field of artificial evolution.

Amino Acid Sequence↗

PubMed1982

Computer-assisted sequencing, interval graphs, and molecular evolution.

In 1945, Fox developed the strategy for sequencing long proteins by using overlapping fragments. We show how the formal mathematical technique for the construction of interval graphs (Gilmore and Hoffman, 1964) is useful both pedagogically for understanding the underlying logic of sequencing linear molecules and is more amenable to automation because of its algorithmic nature. We also present a computer program, that employs the interval graph algorithm, which can be used to sequence proteins when given digest data. An example is given to illustrate all the steps involved in the algorithmic processing of the data. The need for such developments with respect to molecular evolution is discussed.

Amino Acid Sequence↗

PubMed2006

Phylogenetic analysis of honey bee behavioral evolution.

DNA sequences from three mitochondrial (rrnL, cox2, nad2) and one nuclear gene (itpr) from all 9 known honey bee species (Apis), a 10th possible species, Apis dorsata binghami, and three outgroup species (Bombus terrestris, Melipona bicolor and Trigona fimbriata) were used to infer Apis phylogenetic relationships using Bayesian analysis. The dwarf honey bees were confirmed as basal, and the giant and cavity-nesting species to be monophyletic. All nodes were strongly supported except that grouping Apis cerana with A. nigrocincta. Two thousand post-burnin trees from the phylogenetic analysis were used in a Bayesian comparative analysis to explore the evolution of dance type, nest structure, comb structure and dance sound within Apis. The ancestral honey bee species was inferred with high support to have nested in the open, and to have more likely than not had a silent vertical waggle dance and a single comb. The common ancestor of the giant and cavity-dwelling bees is strongly inferred to have had a buzzing vertical directional dance. All pairwise combinations of characters showed strong association, but the multiple comparisons problem reduces the ability to infer associations between states between characters. Nevertheless, a buzzing dance is significantly associated with cavity-nesting, several vertical combs, and dancing vertically, a horizontal dance is significantly associated with a nest with a single comb wrapped around the support, and open nesting with a single pendant comb and a silent waggle dance.

Animals↗

PubMed1985

Plant transposable elements generate the DNA sequence diversity needed in evolution.

Two germinal and 16 somatic reversion events induced by the Enhancer (En) transposable element system at the wx-8::Spm-I8 allele of Zea mays were cloned and studied by sequence analysis. Excision of the Spm-I8 receptor element from the wx gene results in various mutant DNA sequences. This leads to altered gene products, some of which are still capable of restoring the wild-type phenotype. Possible 'foot-print' sequences that may have arisen by the excision of transposable elements were observed when intron sequences of the wild-type (wx+) and mutant (wx-m8) alleles of the wx gene were compared. The sequence divergence generated by visitation of a locus by plant transposable elements is discussed with respect to the molecular evolution of the new gene functions.

Base Sequence↗

PubMed1994

Acquisition and rearrangement of sequence motifs in the evolution of bacteriophage tail fibres.

Molecular analysis reveals a surprising sharing of short gene segments among a variety of large double-stranded DNA bacteriophages of enteric bacteria. Ancestral genomes from otherwise unrelated phages, including lambda, Mu, P1, P2 and T4, must have exchanged parts of their tail-fibre genes. Individual genes appear as mosaics with parts derived from a common gene pool. Therefore, horizontal gene transfer emerges as a major factor in the evolution of a specific part of phage genomes. Current concepts of homologous recombination cannot account for the formation of such chimeric genes and the recombinational mechanisms responsible are not known. However, recombination sites for DNA invertases and recombination site-like sequences are present at the boundaries of gene segments conferring the specificity for the host receptor. This, together with the properties of the DNA inversion mechanism, suggests that these site-specific recombination enzymes could be responsible for the exchange of host-range determinants.

Base Sequence↗

PubMed2002

Evolution of Ig DNA sequence to target specific base positions within codons for somatic hypermutation.

Ig variable (V) region genes are subjected to a somatic hypermutation process as B lymphocytes participate in immune reactions to protein Ags. Although little is known regarding the mechanism of mutagenesis, a consistent hierarchy of trinucleotide target preferences is evident. Analysis of trinucleotide regional distributions predicted and we now empirically confirm the surprising finding that the framework 2 region of kappa V region genes is highly mutable despite its importance to the structural integrity and function of the Ab molecule. Interestingly, much of this mutability appears to be focused on the third codon position where synonymous substitutions are most likely to occur. We also observed a trend for high predicted mutability for codon positions 1 and 2 in complementarity-determining regions. Consequently, amino acid replacements should occur at a higher rate in complementarity-determining regions than in framework regions due to the distribution and subsequent targeting of microsequences by the mutation mechanism. Our results reveal a subtle tier of V region gene evolution in which DNA sequence has been molded to direct mutations to specific base positions within codons in a manner that minimizes damage and maximizes the benefits of the somatic hypermutation process.

Animals↗

PubMed1989

Nucleotide sequence, genomic organization and evolution of a major repetitive DNA family in tilapia (Oreochromis mossambicus/hornorum).

A highly repetitive DNA sequence from tilapia (Oreochromis mossambicus/hornorum) has been cloned and sequenced. It is a tandemly arrayed sequence of 237 bp and constitutes 7% of the fish genome. The copy number of the repeat is approximately 3 x 10(5) per haploid genome. DNA sequence analysis of 7 cloned repeats revealed a high degree of conservation of the monomeric unit. Within the monomeric unit, a 9 bp AT rich motif is regularly spaced approximately 30 bp apart and may represent the progenitor of the amplified sequence. One cloned repeat, Ti-14, contained a 30 bp deletion at a position flanked by a 7 bp direct repeat. The Ti-14 sequence appears to have been amplified independently of the major 237 bp tandem array. A higher-order repeat unit, defined by longer-range periodicities revealed by restriction endonuclease digestion, is further imposed on the tandem array.

Animals↗

PubMed1999

Multiple substitutions affect the phylogenetic utility of cytochrome b and 12S rDNA data: examining a rapid radiation in leporid (Lagomorpha) evolution.

Partial sequences of two mitochondrial genes, the 12S ribosomal gene (739 bp) and the cytochrome b gene (672 bp), were analyzed in hopes of reconstructing the evolutionary relationships of 11 leporid species, representative of seven genera. However, partial cytochrome b sequences were of little phylogenetic value in this study. A suite of pairwise comparisons between taxa revealed that at the intergeneric level, the cytochrome b gene is saturated at synonymous coding positions due to multiple substitution events. Furthermore, variation at the nonsynonymous positions is limited, rendering the cytochrome b gene of little phylogenetic value for assessing the relationships between leporid genera. If the cytochrome b data are analyzed without accounting for these two classes of nucleotides (i.e., synonymous and nonsynonymous sites), one may incorrectly conclude that signal exists in the cytochrome b data. The mitochondrial 12S rRNA gene, on the other hand, has not experienced excessive saturation at either stem or loop positions. Phylogenies reconstructed from the 12S rDNA data support hypotheses based on fossil evidence that African rock rabbits (Pronolagus) are outside of the main leporid stock and that leporids experienced a rapid radiation. However, the molecular data suggest that this radiation event occurred in the mid-Miocene several millions of years earlier than the Pleistocene dates suggested by paleontological evidence.

Animals↗

PubMed2005

Origin and evolution of viruses: escaped DNA/RNA sequences as evolutionary accelerators and natural biological weapons.

Knowledge of the origin and evolution of viruses could provide a better understanding of a number of phenomena in the field of evolution such as the origin and development of multi-cellular organisms, the rapid diversification of species over the last 600-700 million years and the lack of transitional forms in the evolution of species ("missing links") etc. One of the possible effects of escaped DNA/RNA sequences or viruses on the evolution of multi-cellular organisms, especially vertebrates, could be the phenomenon of horizontal transmission and dissemination of genes. Interestingly, if so, this effect could be considered as a model of primeval and natural genetic engineering. Other possible links between the evolution of multi-cellular organisms and viruses are connected with the fact that viruses represent the source of different forms of selective pressure such as epidemics of infectious diseases, autoimmunity, malignant alteration, reproductive efficiency, etc. At the same time, these two models of "long-term evolutionary relations" could represent "key factors" in the evolution between viruses and multi-cellular organisms. The capability of a genome to produce and emit DNA/RNA sequences or de novo created viruses which can be a vector of genes horizontal transmission and/or cause selective pressure on concurrent or predator species gives a new characteristic to viruses--the possibility of their acting as natural biological weapons. Finally, possibly evolutionary advantages of this genome capability could be one of explanations for the phenomena such as genome instability and its ability to emit DNA/RNA sequences and/or de novo created viruses, as well as evolutionary conservation of this unique phenomena.

Animals↗