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Bluetongue virus evolution: sequence analyses of the genomic S1 segments and major core protein VP7.

The S1 segments, encoding the group-specific antigen, VP7, from the five United States prototype BTV serotypes were cloned as full-length entities. The nucleotide and deduced amino acid sequences of segment S1 of BTV-2 were determined and compared with BTV-10, -11, -13, and -17, completing the sequencing of this cognate gene segment from all five US BTV serotypes. Each segment is 1156 bp long and contains an open reading frame encoding the 349-amino acid VP7 protein. Most (greater than 94%) of the amino acids of VP7 among the serotypes are conserved, including the location (position 255) of a single lysine residue. Secondary structure analyses of VP7 predict a putative eight-stranded beta-barrel between amino acid positions 150 and 250, a structure similar to that observed in ssRNA viruses. The S1 genes are flanked by conserved 5' and 3' noncoding regions. Stem-loop structures are predicted at the 3' end of each gene (nucleotide positions 1058-1097). The S1 segments of BTV-2, -10, -11, and -17 have greater than 93% of the nucleotides conserved, while less than 80% of their bases are identical with BTV-13. Analyses of nucleotide mismatches in each codon position of the VP7 open reading frame, transition frequencies, and evolutionary distances show that of the five, BTV-13 is the most distantly related and that BTV-10 and -17 are the most closely related serotypes. Evolutionary distance calculations of segment L2 from BTV-10, -11, and -17 concur with these observations. Comparison of this relationship with hybridization data of segment M3, which codes for VP5, suggests that BTV-17 has evolved by a combination of genetic drift and genomic reassortment. The data also indicate that the five US BTV serotypes are derived from two distinct gene pools. Evolution distances were used to estimate an evolution rate of 2.2 x 10(-3) nucleotide substitution/site/year for BTV segment S1. This rate is similar to the genes of retroviruses and implies an absence of RNA polymerase proofreading activity for dsRNA viruses.

Amino Acid Sequence↗

The hypercube structure of the genetic code explains conservative and non-conservative aminoacid substitutions in vivo and in vitro.

A representation of the genetic code as a six-dimensional Boolean hypercube is described. This structure is the result of the hierarchical order of the interaction energies of the bases in codon-anticodon recognition. In this paper it is applied to study molecular evolution in vivo and in vitro. In the first case we compared aligned positions in homologous protein sequences and found two different behaviors: (a) There are sites in which the different amino acids may be explained by one or two 'attractor nodes' (coding for the dominating amino acid(s)) and their one-bit neighbors in the codon hypercube; and (b) There are sites in which the amino acids correspond to codons located in closed paths in the hypercube. In the second case we studied the 'Sexual PCR'1 experiment described by Stemmer [Stemmer (1994)] and found that the success of this combination of usual PCR and recombination is in part due to the Gray code structure of the genetic code.

Amino Acids↗

Intergenic region typing (IRT): a rapid molecular approach to the characterization and evolution of Leishmania.

In the New World, Leishmania of the Viannia subgenus cause both cutaneous and mucocutaneous disease. These parasites show considerable intra-species genetic diversity and variation, which complicates taxonomic classification and epidemiology. We have used the variability of the transcribed noncoding regions between the small and large subunit rRNA genes to examine relationships in this group. In a method termed intergenic region typing (IRT), PCR amplification products were obtained for the rapidly evolving 1-1.2-kb internal transcribed spacers (ITS) between the SSU and LSU rRNAs, from 50 parasites isolated from different hosts and geographic areas. Amplified DNAs were digested with 10 different enzymes, and fragment patterns compared after acrylamide gel electrophoresis. High levels of intra- and inter-specific variation were observed, and quantitative similarity comparisons were used to associate different lineages. A complex evolutionary tree was obtained. Some species formed tight clusters (L. equatorensis, L. panamensis, L. guyanensis, L. shawi), while L. braziliensis was highly polymorphic and L. naiffi showed intraspecific distances comparable to the largest obtained within all Viannia. L. colombiensis, L. equatorensis and L. lainsoni clearly represent distinct lineages. Good agreement was obtained with molecular trees based upon isoenzyme or mini-exon repeat sequence comparisons. Overall, IRT appears to be a superb method for epidemiological and taxonomic studies of Leishmania, being sensitive, rapid and quantitative while simultaneously revealing considerable molecular diversity. IRT could also be applied to other nonconserved intergenic regions, including those separating protein-coding genes.

Animals↗

Carbon - the first frontier of information processing.

Information is often encoded as an aperiodic chain of building blocks. Modern digital computers use bits as the building blocks, but in general the choice of building blocks depends on the nature of the information to be encoded. What are the optimal building blocks to encode structural information? This can be analysed by substituting the operations of addition and multiplication of conventional arithmetic with translation and rotation. It is argued that at the molecular level, the best component for encoding discretized structural information is carbon. Living organisms discovered this billions of years ago, and used carbon as the back-bone for constructing proteins that function according to their structure. Structural analysis of polypeptide chains shows that an efficient and versatile structural language of 20 building blocks is needed to implement all the tasks carried out by proteins. Properties of amino acids indicate that the present triplet genetic code was preceded by a more primitive one, coding for 10 amino acids using two nucleotide bases.

Amino Acid Sequence↗

Graphs in sequence spaces: a review of statistical geometry.

Statistical geometry is a method of comparative sequence analysis of genes. Based on the concept of the sequence space of nucleic acids it computes the geometries of sequence sets, mainly quartets, by combining both the vertical and horizontal information content of the sequences. The geometries can be used to deduce, for example, the degree of tree-likeness of the data set without any a priori assumption of an evolution model. Furthermore, statistical geometry allows to detect varying positional substitution rates in sequences. Applications of the method to tRNA sequences have provided an assessment for the age of the genetic code. Furthermore, applications of statistical geometry to homeoboxes as well as different virus families have helped to assign reliable kinship relationships. In addition, a lower bound for the age of the common ancestor of the human and simian immunodeficiency viruses has been established.

DNA, Viral↗

Gene duplication and other evolutionary strategies: from the RNA world to the future.

Beginning with a hypothetical RNA world, it is apparent that many evolutionary transitions led to the complexity of extant species. The duplication of genetic material is rooted in the RNA world. One of two major routes of gene amplification, retroposition, originated from mechanisms that facilitated the transition to DNA as hereditary material. Even in modern genomes the process of retroposition leads to genetic novelties including the duplication of protein and RNA coding genes, as well as regulatory elements and their juxtapositon. We examine whether and to what extent known evolutionary principles can be applied to an RNA-based world. We conclude that the major basic Neo-Darwinian principles that include amplification, variation and selection already governed evolution in the RNA and RNP worlds. In this hypothetical RNA world there were few restrictions on the exchange of genetic material and principles that acted as borders at later stages, such as Weismann's Barrier, the Central Dogma of Molecular Biology, or the Darwinian Threshold were absent or rudimentary. RNA was more than a gene: it had a dual role harboring, genotypic and phenotypic capabilities, often in the same molecule. Nuons, any discrete nucleic acid sequences, were selected on an individual basis as well as in groups. The performance and success of an individual nuon was markedly dependent on the type of other nuons in a given cell. In the RNA world the transition may already have begun towards the linkage of nuons to yield a composite linear RNA genome, an arrangement necessitating the origin of RNA processing. A concatenated genome may have curbed unlimited exchange of genetic material; concomitantly, selfish nuons were more difficult to purge. A linked genome may also have constituted the beginning of the phenotype/genotype separation. This division of tasks was expanded when templated protein biosynthesis led to the RNP world, and more so when DNA took over as genetic material. The aforementioned barriers and thresholds increased and the significance and extent of horizontal gene transfer fluctuated over major evolutionary transitions. At the dawn of the most recent transformation, a fast evolutionary transition that we will be witnessing in our life times, a form of Lamarckism is raising its head.

Animals↗

Clann: investigating phylogenetic information through supertree analyses.

UNLABELLED: Clann has been developed in order to provide methods of investigating phylogenetic information through the application of supertrees. AVAILABILITY: Clann has been precompiled for Linux, Apple Macintosh and Windows operating systems and is available from http://bioinf.may.ie/software/clann. Source code is available on request from the authors. SUPPLEMENTARY INFORMATION: Clann has been written in the C programming language. Source code is available on request.

Algorithms↗

In silico search for functionally similar proteins involved in meiosis and recombination in evolutionarily distant organisms.

Evolutionarily distant organisms have not only orthologs, but also nonhomologous proteins that build functionally similar subcellular structures. For instance, this is true with protein components of the synaptonemal complex (SC), a universal ultrastructure that ensures the successful pairing and recombination of homologous chromosomes during meiosis. We aimed at developing a method to search databases for genes that code for such nonhomologous but functionally analogous proteins. Advantage was taken of the ultrastructural parameters of SC and the conformation of SC proteins responsible for these. Proteins involved in SC central space are known to be similar in secondary structure. Using published data, we found a highly significant correlation between the width of the SC central space and the length of rod-shaped central domain of mammalian and yeast intermediate proteins forming transversal filaments in the SC central space. Basing on this, we suggested a method for searching genome databases of distant organisms for genes whose virtual proteins meet the above correlation requirement. Our recent finding of the Drosophila melanogaster CG17604 gene coding for synaptonemal complex transversal filament protein received experimental support from another lab. With the same strategy, we showed that the Arabidopsis thaliana and Caenorhabditis elegans genomes contain unique genes coding for such proteins.

Animals↗

Prebiotic co-evolution of self-replication and translation or RNA world?

A prebiotic scenario is proposed, based on the recent "domain hypothesis" model (Lahav, 1989, J. molec. Evol. 29, 475-479), suggested for domain propagation of RNA-like molecules in a fluctuating environment. The same system is suggested now not only for the evolution of ribozymes, but also for the evolution of directed peptide synthesis, as follows: Short, self-structured strands (termed prebioectons), each possessing a templatable domain which is chargeable by an amino acid, are the predecessors of tRNA (proto-tRNA). Complementary domains are formed on these prebioectons during an environmental cycle such as wetting-drying, followed by their dissociation from their template domain and ligation, to form the predecessor of mRNA (proto-mRNA). The evolution of directed peptide synthesis is suggested to be based on the ability of the charged prebioectons to attach preferentially to their complementary domains on the proto-mRNA. Two stages of this process are envisioned, namely: (a) Template-directed, random peptide synthesis taking place when non-specifically-charged prebioectons are sequentially attached each to its complementary domain on the proto-mRNA, followed by peptide bond formation. (b) Template-and-sequence-directed peptide synthesis, which can be realized after the "invention" of a catalytic molecule capable of specifically charging a proto-tRNA by an amino acid; this is the crucial evolutionary stage, where a crude genetic code becomes functional. Gradually, catalytic peptides and ribozymes are selected for their functions and evolve, while being encoded in the primitive "memory" of the emerging system. Thus, rather than the RNA monopoly postulated by the RNA World hypothesis, an early co-evolution of primitive enzymes and ribozymes is suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Population genetic implications from sequence variation in four Y chromosome genes.

Some insight into human evolution has been gained from the sequencing of four Y chromosome genes. Primary genomic sequencing determined gene SMCY to be composed of 27 exons that comprise 4,620 bp of coding sequence. The unfinished sequencing of the 5' portion of gene UTY1 was completed by primer walking, and a total of 20 exons were found. By using denaturing HPLC, these two genes, as well as DBY and DFFRY, were screened for polymorphic sites in 53-72 representatives of the five continents. A total of 98 variants were found, yielding nucleotide diversity estimates of 2.45 x 10(-5), 5. 07 x 10(-5), and 8.54 x 10(-5) for the coding regions of SMCY, DFFRY, and UTY1, respectively, with no variant having been observed in DBY. In agreement with most autosomal genes, diversity estimates for the noncoding regions were about 2- to 3-fold higher and ranged from 9. 16 x 10(-5) to 14.2 x 10(-5) for the four genes. Analysis of the frequencies of derived alleles for all four genes showed that they more closely fit the expectation of a Luria-Delbrück distribution than a distribution expected under a constant population size model, providing evidence for exponential population growth. Pairwise nucleotide mismatch distributions date the occurrence of population expansion to approximately 28,000 years ago. This estimate is in accord with the spread of Aurignacian technology and the disappearance of the Neanderthals.

Aged↗

A single amino acid mutation contributes to adaptive beach mouse color pattern.

Natural populations of beach mice exhibit a characteristic color pattern, relative to their mainland conspecifics, driven by natural selection for crypsis. We identified a derived, charge-changing amino acid mutation in the melanocortin-1 receptor (Mc1r) in beach mice, which decreases receptor function. In genetic crosses, allelic variation at Mc1r explains 9.8% to 36.4% of the variation in seven pigmentation traits determining color pattern. The derived Mc1r allele is present in Florida's Gulf Coast beach mice but not in Atlantic coast mice with similar light coloration, suggesting that different molecular mechanisms are responsible for convergent phenotypic evolution. Here, we link a single mutation in the coding region of a pigmentation gene to adaptive quantitative variation in the wild.

Adaptation, Biological↗

Developmental patterning and evolution of the mammalian viscerocranium: genetic insights into comparative morphology.

The vertebrate cranium is generally classified into the neurocranium and the viscerocranium. The latter is derived from the neural crest and so is the prechordal portion of the neurocranium. A view we favor considers the prechordal neurocranium as the premandibular component of the viscerocranium, and the vertebrate skull to consist of the neural crest-derived viscerocranium and the mesodermal neurocranium. Of these developmental units, only the viscerocranium appears to have completely segmented metamerical organization. The Hox code which is known to function in specification of the viscerocranium does not extend rostrally into the mandibular and premandibular segments. By genetic manipulation of rostrally expressed non-Hox homeobox genes, the patterning mechanism of the head is now demonstrated to be more complicated than isomorphic registration of the Hox code to pharyngeal arches. The phenotype by haplo-insufficiency of Otx2 gene, in particular, implies the premandibular cranium shares a common specification mechanism with the mandibular arch. Our interpretation of the metamerical plan of the viscerocranium offers a new scheme of molecular codes associated with the vertebrate head evolution.

Animals↗

Evidence of selection on silent site base composition in mammals: potential implications for the evolution of isochores and junk DNA.

It has been suggested that mutation bias is the major determinant of base composition bias at synonymous, intron, and flanking DNA sites in mammals. Here I test this hypothesis using population genetic data from the major histocompatibility genes of several mammalian species. The results of two tests are inconsistent with the mutation hypothesis in coding, noncoding, CpG-island, and non-CpG-island DNA, but are consistent with selection or biased gene conversion. It is argued that biased gene conversion is unlikely to affect silent site base composition in mammals. The results therefore suggest that selection is acting upon silent site G + C content. This may have broad implications, since silent site base composition reflects large-scale variation in G + C content along mammalian chromosomes. The results therefore suggest that selection may be acting upon the base composition of isochores and large sections of junk DNA.

Alleles↗

Genomic exploration of the hemiascomycetous yeasts: 3. Methods and strategies used for sequence analysis and annotation.

The primary analysis of the sequences for our Hemiascomycete random sequence tag (RST) project was performed using a combination of classical methods for sequence comparison and contig assembly, and of specifically written scripts and computer visualization routines. Comparisons were performed first against DNA and protein sequences from Saccharomyces cerevisiae, then against protein sequences from other completely sequenced organisms and, finally, against protein sequences from all other organisms. Blast alignments were individually inspected to help recognize genes within our random genomic sequences despite the fact that only parts of them were available. For each yeast species, validated alignments were used to infer the proper genetic code, to determine codon usage preferences and to calculate their degree of sequence divergence with S. cerevisiae. The quality of each genomic library was monitored from contig analysis of the DNA sequences. Annotated sequences were submitted to the EMBL database, and the general annotation tables produced served as a basis for our comparative description of the evolution, redundancy and function of the Hemiascomycete genomes described in other articles of this issue.

Amino Acid Sequence↗