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PubMed2002

Postgenomic chemical ecology: from genetic code to ecological interactions.

Environmental response genes are defined as those encoding proteins involved in interactions external to the organism, including interactions among organisms and between the organism and its abiotic environment. The general characteristics of environmental response genes include high diversity, proliferation by duplication events, rapid rates of evolution, and tissue- or temporal-specific expression. Thus, environmental response genes include those that encode proteins involved in the manufacture, binding, transport, and breakdown of semiochemicals. Postgenomic elucidation of the function of such genes requires an understanding of the chemical ecology of the organism and, in particular, of the "small molecules" that act as selective agents either by promoting survival or causing selective mortality. In this overview, the significance of several groups of environmental response genes is examined in the context of chemical ecology. Cytochrome P-450 monooxygenases provide a case in point; these enzymes are involved in the biosynthesis of furanocoumarins (furocoumarins), toxic allelochemicals, in plants, as well as in their detoxification by lepidopterans. Biochemical innovations in insects and plants have historically been broadly defined in a coevolutionary context. Considerable insight can be gained by defining with greater precision components of those broad traits that contribute to diversification. Molecular approaches now allow chemical ecologists to characterize specifically those biochemical innovations postulated to lead to adaptation and diversification in plant/insect interactions.

Animals↗

PubMed1995

41 kilobases of analyzed sequence from the pseudoautosomal and sex-determining regions of the short arm of the human Y chromosome.

Determination of 41.2 kb of Y chromosome genomic sequence has been made from a cosmid that spans the Yp pseudoautosomal boundary and includes 18.5 kb of sequence from the patient-defined sex-determining region of the Y chromosome. An AceDB database of the sequence and the analysis data have been produced as a resource for studies of the evolution and population genetics of the Y chromosome. Comparison of the 18.5 kb from the sex determining region to the sex determining region of mouse does not locate any areas of similarity outside SRY/Sry. Indeed, no coding regions other than those previously reported can be detected anywhere in the 41 kb. The Y-specific and pseudoautosomal portions of this sequence have different repeat sequence and GC contents: this may have relevance both to the events defining the pseudoautosomal boundary and to the course of sequence evolution in the absence of recombination.

Animals↗

PubMed2006

Birth of a chimeric primate gene by capture of the transposase gene from a mobile element.

The emergence of new genes and functions is of central importance to the evolution of species. The contribution of various types of duplications to genetic innovation has been extensively investigated. Less understood is the creation of new genes by recycling of coding material from selfish mobile genetic elements. To investigate this process, we reconstructed the evolutionary history of SETMAR, a new primate chimeric gene resulting from fusion of a SET histone methyltransferase gene to the transposase gene of a mobile element. We show that the transposase gene was recruited as part of SETMAR 40-58 million years ago, after the insertion of an Hsmar1 transposon downstream of a preexisting SET gene, followed by the de novo exonization of previously noncoding sequence and the creation of a new intron. The original structure of the fusion gene is conserved in all anthropoid lineages, but only the N-terminal half of the transposase is evolving under strong purifying selection. In vitro assays show that this region contains a DNA-binding domain that has preserved its ancestral binding specificity for a 19-bp motif located within the terminal-inverted repeats of Hsmar1 transposons and their derivatives. The presence of these transposons in the human genome constitutes a potential reservoir of approximately 1,500 perfect or nearly perfect SETMAR-binding sites. Our results not only provide insight into the conditions required for a successful gene fusion, but they also suggest a mechanism by which the circuitry underlying complex regulatory networks may be rapidly established.

Amino Acid Sequence↗

PubMed1991

Secondary structure as a constraint on the evolution of a plant viral satellite RNA.

The genetic variability and evolution of the satellite RNA (satRNA) of cucumber mosaic virus (CMV) was analyzed. Twenty-five CMV-satRNAs compared clustered into three main groups, and no correlation was found between genetic proximity and other characteristics (pathogenicity, geographical origin) of the satRNAs. Values for the number of nucleotide substitutions per site between any two satRNAs suggest that divergence is checked by functional constraints. The analysis of mutations relative to an ancestral sequence, and the number of substitutions per site at first, second and third positions of codons in putative open reading frames, show that the variation of CMV-satRNAs does not follow a pattern typical of coding sequences, and indicates that preservation of the sequence of encoded products is not a constraint to evolution. On the other hand, when the observed variation was analyzed relative to a secondary structure model proposed for CMV-satRNAs, several lines of evidence indicated that the maintenance of the secondary structure is a constraint to evolution: the number of substitutions per site, the number of point insertions and deletions and the number of base substitutions that would disrupt base-pairing were significantly higher for unpaired than for base-paired positions. Also, compensatory mutations at base-paired positions occurred more frequently than expected from random. The results suggest that CMV-satRNAs are non-coding, functional RNAs whose biology would be determined by their direct interaction with components of the host and/or the helper virus.

Base Composition↗

PubMed2003

Programming peptidomimetic syntheses by translating genetic codes designed de novo.

Although the universal genetic code exhibits only minor variations in nature, Francis Crick proposed in 1955 that "the adaptor hypothesis allows one to construct, in theory, codes of bewildering variety." The existing code has been expanded to enable incorporation of a variety of unnatural amino acids at one or two nonadjacent sites within a protein by using nonsense or frameshift suppressor aminoacyl-tRNAs (aa-tRNAs) as adaptors. However, the suppressor strategy is inherently limited by compatibility with only a small subset of codons, by the ways such codons can be combined, and by variation in the efficiency of incorporation. Here, by preventing competing reactions with aa-tRNA synthetases, aa-tRNAs, and release factors during translation and by using nonsuppressor aa-tRNA substrates, we realize a potentially generalizable approach for template-encoded polymer synthesis that unmasks the substantially broader versatility of the core translation apparatus as a catalyst. We show that several adjacent, arbitrarily chosen sense codons can be completely reassigned to various unnatural amino acids according to de novo genetic codes by translating mRNAs into specific peptide analog polymers (peptidomimetics). Unnatural aa-tRNA substrates do not uniformly function as well as natural substrates, revealing important recognition elements for the translation apparatus. Genetic programming of peptidomimetic synthesis should facilitate mechanistic studies of translation and may ultimately enable the directed evolution of small molecules with desirable catalytic or pharmacological properties.

Base Sequence↗

PubMed2006

An analytical model of gene evolution with 9 mutation parameters: an application to the amino acids coded by the common circular code.

We develop here an analytical evolutionary model based on a trinucleotide mutation matrix 64 x 64 with nine substitution parameters associated with the three types of substitutions in the three trinucleotide sites. It generalizes the previous models based on the nucleotide mutation matrices 4 x 4 and the trinucleotide mutation matrix 64 x 64 with three and six parameters. It determines at some time t the exact occurrence probabilities of trinucleotides mutating randomly according to these nine substitution parameters. An application of this model allows an evolutionary study of the common circular code [Formula: see text] of eukaryotes and prokaryotes and its 12 coded amino acids. The main property of this code [Formula: see text] is the retrieval of the reading frames in genes, both locally, i.e. anywhere in genes and in particular without a start codon, and automatically with a window of a few nucleotides. However, since its identification in 1996, amino acid information coded by [Formula: see text] has never been studied. Very unexpectedly, this evolutionary model demonstrates that random substitutions in this code [Formula: see text] and with particular values for the nine substitutions parameters retrieve after a certain time of evolution a frequency distribution of these 12 amino acids very close to the one coded by the actual genes.

Amino Acids↗

PubMed1991

Proto-splice site model of intron origin.

It is proposed that nuclear pre-mRNA introns (classical introns) were first generated as by-products during the evolution of alternative splicing. They were formed whenever two splice sites within the coding sequence of ancestral genes were used at a frequency that removed the coding constraint from the intervening sequence. Once introns had evolved, it is suggested that they were spread by the splicing machinery which inserted them into proto or cryptic-splice sites of other genes by reverse splicing, so giving rise to genes that have introns yet are not alternatively spliced. It is argued that 5' and 3' splice sites evolved from common ancestral splice sites, referred to as proto-splice sites, that were bidirectional and had a core consensus sequence of C or A, A, G, R, which remains today as the immediate flanking sequence of most introns. The ancestral splicing machinery, although inefficient, would have been capable of generating vast mRNA diversity by splicing between proto-splice sites. Natural selection would be expected to have preserved mutations that increased the amounts of advantageously spliced mRNA. It is argued that this process drove the evolution of present 5' and 3' splice sites from a subset of proto-splice sites and also drove the evolution of a more efficient splicing machinery. The positions of most introns that evolved directly from the coding sequence would be expected to correlate with protein structure.

Animals↗

PubMed2006

Informational structure of two closely related eukaryotic genomes.

Attempts to identify a species on the basis of its DNA sequence on purely statistical grounds have been formulated for more than a decade. The most prominent of such genome signatures relies on neighborhood correlations (i.e., dinucleotide frequencies) and, consequently, attributes species identification to mechanisms operating on the dinucleotide level (e.g., neighbor-dependent mutations). For the examples of Mus musculus and Rattus norvegicus we analyze short- and intermediate-range statistical correlations in DNA sequences. These correlation profiles are computed for all chromosomes of the two species. We find that with increasing range of correlations the capacity to distinguish between the species on the basis of this correlation profile is getting better and requires ever shorter sequence segments for obtaining a full species separation. This finding suggests that distinctive traits within the sequence are situated beyond the level of few nucleotides. The large-scale statistical patterning of DNA sequences on which such genome signatures are based is thus substantially determined by mobile elements (e.g., transposons and retrotransposons). The study and interspecies comparison of such correlation profiles can, therefore, reveal features of retrotransposition, segmental duplications, and other processes of genome evolution.

Animals↗

PubMed2002

Ratios of radical to conservative amino acid replacement are affected by mutational and compositional factors and may not be indicative of positive Darwinian selection.

The ratio of radical to conservative amino acid replacements is frequently used to infer positive Darwinian selection. This method is based on the assumption that radical replacements are more likely than conservative replacements to improve the function of a protein. Therefore, if positive selection plays a major role in the evolution of a protein, one would expect the radical-conservative ratio to exceed the expectation under neutrality. Here, we investigate the possibility that factors unrelated to selection, i.e., transition-transversion ratio, codon usage, genetic code, and amino acid composition, influence the radical-conservative replacement ratio. All factors that have been studied were found to affect the radical-conservative replacement ratio. In particular, amino acid composition and transition-transversion ratio are shown to have the most profound effects. Because none of the studied factors had anything to do with selection (positive or otherwise) and also because all of them (singly or in combination) affected a measure that was supposed to be indicative of positive selection, we conclude that selectional inferences based on radical-conservative replacement ratios should be treated with suspicion.

Amino Acid Substitution↗

PubMed2003

Identification and genomic distribution of gypsy like retrotransposons in Citrus and Poncirus.

Transposable elements might be importantly involved in citrus genetic instability and genome evolution. The presence of gypsy like retrotransposons, their heterogeneity and genomic distribution in Citrus and Poncirus, have been investigated. Eight clones containing part of the POL coding region of gypsy like retrotransposons have been isolated from a commercial variety of Citrus clementina, one of the few sexual species in Citrus. Four of the eight clones might correspond to active elements given that they present all the conserved motifs described in the literature as essential for activity, no in-frame stop codon and no frame-shift mutation. High homology has been found between some of these citrus elements and retroelements within a resistance-gene cluster from potato, another from Poncirus trifoliata and two putative resistance polyproteins from rice. Nested copies of gypsy like elements are scattered along the Citrus and Poncirus genomes. The results on genomic distribution show that these elements were introduced before the divergence of both genera and evolved separately thereafter. IRAPs based on gypsy and copia types of retrotransposons seem to distribute differently, therefore gypsy based IRAPs prove a new, complementary set of molecular markers in Citrus to study and map genetic variability, especially for disease resistance. Similarly to copia-derived IRAPs, the number of copies and heterozygosity values found for gypsy derived IRAPs are lower in Poncirus than in Citrus aurantium, which is less apomictic and the most usual rootstock for clementines until 1970.

Amino Acid Sequence↗

PubMed1987

The evolution of nonhuman primate social behavior.

A review of the recent literature concerning evolutionary mechanisms and possible genetic contributions to social behavior reveals a concentration on function rather than mechanism. Although functional consequences may influence future genetic changes in a population, they do not necessarily reflect evolutionary history. More important, genes cannot code for functions. Only when the anatomical structures and behavioral patterns of individuals are described can we study genetic contributions to social organization. Discussions of function in the abstract, without specification of mechanism, do not fall within the realm of scientific testing.

Animals↗

PubMed2004

A chromosome bin map of 2148 expressed sequence tag loci of wheat homoeologous group 7.

The objectives of this study were to develop a high-density chromosome bin map of homoeologous group 7 in hexaploid wheat (Triticum aestivum L.), to identify gene distribution in these chromosomes, and to perform comparative studies of wheat with rice and barley. We mapped 2148 loci from 919 EST clones onto group 7 chromosomes of wheat. In the majority of cases the numbers of loci were significantly lower in the centromeric regions and tended to increase in the distal regions. The level of duplicated loci in this group was 24% with most of these loci being localized toward the distal regions. One hundred nineteen EST probes that hybridized to three fragments and mapped to the three group 7 chromosomes were designated landmark probes and were used to construct a consensus homoeologous group 7 map. An additional 49 probes that mapped to 7AS, 7DS, and the ancestral translocated segment involving 7BS also were designated landmarks. Landmark probe orders and comparative maps of wheat, rice, and barley were produced on the basis of corresponding rice BAC/PAC and genetic markers that mapped on chromosomes 6 and 8 of rice. Identification of landmark ESTs and development of consensus maps may provide a framework of conserved coding regions predating the evolution of wheat genomes.

Chromosome Mapping↗

PubMed1996

Primary and secondary structure analyses of the rDNA group-I introns of the Zygnematales (Charophyta).

The Zygnematales (Charophyta) contain a group-I intron (subgroupIC1) within their nuclear-encoded small subunit ribosomal DNA (SSU rDNA) coding region. This intron, which is inserted after position 1506 (relative to the SSU rDNA of Escherichia coli), is proposed to have been vertically inherited since the origin of the Zygnematales approximately 350-400 million years ago. Primary and secondary structure analyses were carried out to model group-I intron evolution in the Zygnematales. Secondary structure analyses support genetic data regarding sequence conservation within regions known to be functionally important for in vitro self-splicing of group-I introns. Comparisons of zygnematalean group-I intron secondary structures also provided some new insights into sequences that may have important roles in in vivo RNA splicing. Sequence analyses showed that sequence divergence rates and the nucleotide compositions of introns and coding regions within any one taxon varied widely, suggesting that the "1506" group-I introns and rDNA coding regions in the Zygnematales evolve independently.

Base Composition↗

PubMed1995

Were RNA replication and translation directly coupled in the RNA (+protein?) World?

The ribosome is proposed to have evolved from an ancestor that simultaneously replicated and translated template RNA. At its decoding site, this ancestor to the ribosome carried a ribozyme that assembled product RNA by sequentially ligating anticodon triplets excised from tRNAs. This ribozyme was the ancestor of the Group I introns, which are still present on some ribosomal RNA precursors. Coupling of reversible RNA replication by transesterification with the thermodynamically favourable process of transpeptidation provides a rationale for the evolution of the complete ribosome as a replicase for large RNAs in the RNA (+protein?) world. A detailed and experimentally verifiable mechanism can be proposed for simultaneous replication and translation. Sequence requirements for recognition of the decoding complex as a substrate helix by these ribozymes are consistent with earlier models for the origin of the genetic code, but require an indirect mode for ribosomal self-replication. This proposal has the potential to explain the location of Group I introns in the anticodon loops of some tRNAs.

Animals↗

PubMed2000

Concurrent neutral evolution of mRNA secondary structures and encoded proteins.

Messenger RNA sequences often have to preserve functional secondary structure elements in addition to coding for proteins. We present a statistical analysis of retroviral mRNA which supports the hypothesis that the natural genetic code is adapted to such complementary coding. These sequences are still able to explore efficiently the space of possible proteins by point mutations. This is borne out by the observation that, in stem regions of retroviral mRNA foldings, silent mutations on one strand are preferentially accompanied by conservative mutations on the other. Distances between amino acids based on physicochemical properties are used to quantify the conservation of protein function under the constraint of maintained RNA secondary structure. We find that preservation of RNA secondary structure by compensatory mutations is evolutionary compatible with the efficient search for new variants on the protein level.

Base Sequence↗

PubMed2001

Genetic conflict, genomic imprinting and establishment of the epigenotype in relation to growth.

Genomic imprinting is the process that differentially modifies the parental alleles at certain genetic loci in the parental germlines. Such modifications of DNA and chromatin are somatically heritable and cause unequal expression of the parental alleles during subsequent development. In mammals, imprinted genes encode a relatively small number of functionally heterogeneous proteins. Nevertheless, imprinted genes exert important effects, primarily on fetal development, and their deregulation is implicated in a variety of pathologies including sporadic, inherited and induced growth disorders. Imprinted loci show several unusual structural and functional characteristics that may be related to mechanistic aspects of mono-allelic expression or to modes of evolution of imprinted genetic loci. Typically, imprinted genes are clustered in certain genomic regions and have relatively reduced intronic DNA content relative to non-imprinted genes. In addition, their regulatory regions frequently contain a combination of features including tandem repeats associated with differentially methylated CpG islands and overlapping transcription of coding or non-coding RNAs. The evolution of imprinting can be understood as the stable outcome of sexual selection acting differently on the parental alleles of genes that influence parental investment in offspring. Consistent with this explanation, imprinted genes are expressed predominantly during embryonic and postnatal development in mammals and in the developing endosperm of plants, and maternal or paternal expression at imprinted loci is associated with reduced or increased parental investment, respectively. Such selective forces have implications for understanding mechanistic aspects of genome reprogramming in the early mammalian embryo.

Animals↗

PubMed1992

Intron evolution: a statistical comparison of two models.

The two most frequently occurring explanations for the existence and distribution of introns in the genes of different species are: (1) introns are remnants of the original genetic material. (2) Introns were introduced during evolution. We construct mathematical models corresponding to these two explanations, and calculate the probabilities that the intron distribution in genes from different species coding for actin, alpha-tubulin, triosephosphate isomerase and superoxide dismutase are described by these models. In both models, the branch lengths as well as the structure of the corresponding evolutionary tree is taken into account. Every branch in the evolutionary tree is assumed to have its own individual rate of loss of introns for the first model and rate of gain of introns for the second model. These rate constants are estimated from the actual number of introns. Using the rate constants we stimulate the intron evolution and calculate the probabilities that the actual intron arrangements are produced. The results for actin and alpha-tubulin, which are the two genes we have the most data for, favor the model corresponding conjecture (1), i.e. the idea that introns are old. This contradicts the results from an earlier attempt to model intron evolution where almost the same data was used (Dibb & Newman, 1989, EMBO J. 8, 2015-2021).

Actins↗

PubMed1999

Directed molecular evolution.

We propose the existence of a relationship of stereochemical complementarity between gene sequences that code for interacting components: nucleic acid-nucleic acid, protein-protein and protein-nucleic acid. Such a relationship would impose evolutionary constraints on the DNA sequences themselves, thus retaining these sequences and governing the direction of the evolutionary process. Therefore, we propose that prebiotic, template-directed autocatalytic synthesis of mutally cognate peptides and polynucleotides resulted in their amplification and evolutionary conservation in contemporary prokaryotic and eukaryotic organisms as a genetic regulatory apparatus. If this proposal is correct, then the relationships between the sequences in DNA coding for these interactions constitute a life code of which the genetic code is only one aspect of the many related interactions encoded in DNA.

Base Sequence↗