SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
We have determined the nucleotide sequence of the Pelargonium x hortorum ORF2280 homolog, the largest gene in the plastid genome of most land plants, and compared it to published homologs from Nicotiana tabacum, Epifagus virginiana, Spinacia oleracea, and Marchantia polymorpha. Multiple alignment of protein sequences requires an extraordinary number of gaps, indicating a very high frequency of insertion/deletion events during the evolution of the protein; however, the overall predicted size of the protein varies relatively little among the five species. At 2,109 codons, the Pelargonium gene is smaller than other land plant ORF2280 homologs and exhibits a rate of nucleotide substitution several times higher relative to Nicotiana, Epifagus, and Spinacia. Southern-blot and restriction-mapping studies were carried out to uncover length variation in ORF2280 homologs from 279 species (representing 111 families) of angiosperms. In many independent angiosperm lineages, this gene has sustained deletions ranging in size from 200 bp to almost 6 kb. Based on the severity of deletions, we postulate that the chloroplast homolog of ORF2280 has become nonfunctional in at least four independent lineages of angiosperms.
The gene for bovine interphotoreceptor retinoid-binding protein (IRBP) has been cloned, and its nucleotide sequence has been determined. The IRBP gene is about 11.6 kilobase pairs (kb) and contains four exons and three introns. It transcribed into a large mRNA of approximately 6.4 kb and translated into a large protein of 145,000 daltons. To prove the identity of the genomic clone, we determined the protein sequence of several tryptic and cyanogen bromide fragments of purified bovine IRBP protein and localized them in the protein predicted from its nucleotide sequence. There is a 4-fold repeat structure in the protein sequence with 30-40% sequence identity and many conservative substitutions between any two of the four protein repeats. The third and fourth repeats are the most similar pair. All three of the introns in the IRBP gene fall in the fourth protein repeat. Two of the exons, the first and the fourth, are large, 3173 and 2447 bases, respectively. The introns are each about 1.5-2.2 kb long. The human IRBP gene has a sequence that is similar to one of the introns from the bovine gene. The unexpected gene structure and protein repeat structure in the bovine gene lead us to propose a model for the evolution of the IRBP gene.
Prion diseases are invariably fatal neurodegenerative diseases that affect some mammalian species, including humans. These diseases are caused by the misfolding of the cellular prion protein (PrPC) into a pathologic isoform (PrPSc). The prion protein is highly conserved across mammals. However, some species present lower susceptibility to prion diseases than others. This behavior is likely explained by the resistance of these animal species' prion proteins to acquire a pathological conformation. Therefore, the tertiary structure and interspecific variations encoded in the primary structure determine a PrP proneness to misfolding. For this reason, we studied the PRNP gene from a phylogenetic perspective, potentially unveiling evolutionary events related to prion diseases. We generated a database of mammalian PRNP sequences and constructed phylogenetic trees based on nucleotide sequence variations. We aligned 1146 PRNP gene sequences from 901 different mammalian species and built a PRNP gene-based phylogenetic tree. Classical phylogenetic orders tend to maintain their clustering in the PRNP gene tree. Nonetheless, the few differences found may shed some light on potential evolutionary constraints posed by prion disorders. Moreover, this phylogenetic study was combined with an in vitro misfolding study. Protein Misfolding Shaking Amplification (PMSA) was used to evaluate the tendency of many of these proteins to misfold. This comprehensive analysis spanned a wide range of mammalian prion protein sequences and included analysis of different variants with a focus on the human rs1799990 locus (c.385A > G, p.Met129Val). This variant, widely linked to prion disease susceptibility in humans, is explored in the context of its evolutionary origins. All in all, our PRNP gene-based tree, despite showing some topological differences with the reference species tree that could be in some cases related to prion disease susceptibility, is not significantly distinct. Indicating that the proneness of a PrP variant to misfold spontaneously has not shaped the evolution of this gene.
Mapping nucleotide sequences onto a "DNA walk" produces a novel representation of DNA that can then be studied quantitatively using techniques derived from fractal landscape analysis. We used this method to analyze 11 complete genomic and cDNA myosin heavy chain (MHC) sequences belonging to 8 different species. Our analysis suggests an increase in fractal complexity for MHC genes with evolution with vertebrate > invertebrate > yeast. The increase in complexity is measured by the presence of long-range power-law correlations, which are quantified by the scaling exponent alpha. We develop a simple iterative model, based on known properties of polymeric sequences, that generates long-range nucleotide correlations from an initially noncorrelated coding region. This new model-as well as the DNA walk analysis-both support the intron-late theory of gene evolution.
BACKGROUND: The potential adaptive significance of transposable elements (TEs) to the host genomes in which they reside is a topic that has been hotly debated by molecular evolutionists for more than two decades. Recent genomic analyses have demonstrated that TE fragments are associated with functional genes in plants and animals. These findings suggest that TEs may contribute significantly to gene evolution. RESULTS: We have analyzed two transposable elements associated with genes in the sequenced Drosophila melanogaster y; cn bw sp strain. A fragment of the Antonia long terminal repeat (LTR) retrotransposon is present in the intron of Chitinase 3 (Cht3), a gene located within the constitutive heterochromatin of chromosome 2L. Within the euchromatin of chromosome 2R a full-length Burdock LTR retrotransposon is located immediately 3' to cathD, a gene encoding cathepsin D. We tested for the presence of these two TE/gene associations in strains representing 12 geographically diverse populations of D. melanogaster. While the cathD insertion variant was detected only in the sequenced y; cn bw sp strain, the insertion variant present in the heterochromatic Cht3 gene was found to be fixed throughout twelve D. melanogaster populations and in a D. mauritiana strain suggesting that it maybe of adaptive significance. To further test this hypothesis, we sequenced a 685bp region spanning the LTR fragment in the intron of Cht3 in strains representative of the two sibling species D. melanogaster and D. mauritiana (approximately 2.7 million years divergent). The level of sequence divergence between the two species within this region was significantly lower than expected from the neutral substitution rate and lower than the divergence observed between a randomly selected intron of the Drosophila Alcohol dehydrogenase gene (Adh). CONCLUSIONS: Our results suggest that a 359 bp fragment of an Antonia retrotransposon (complete LTR is 659 bp) located within the intron of the Drosophila melanogaster Cht3 gene is of adaptive evolutionary significance. Our results are consistent with previous suggestions that the presence of TEs in constitutive heterochromatin may be of significance to the expression of heterochromatic genes.
The DAZ gene cluster on the human Y chromosome is a candidate for the Azoospermia Factor (AZFc). According to the current evolutionary model, the DAZ cluster derived from the autosomal homolog DAZL1 through duplications and rearrangements and is confined to Old World monkeys, apes and humans. To study functional and evolutionary aspects of this gene family we have isolated from a cynomolgus (Old World) monkey testis cDNA library the Y chromosomal cynDAZ and the autosomal cynDAZL1 cDNA. cynDAZL1 contains one DAZ repeat and displays high homology to human DAZL1. cynDAZ comprises 11 repeats, each consisting of exons 7 and 8, whereas the human DAZ cDNA repeat units contain predominantly exon 7. Genomic studies revealed the same amplific- ation events of a 2.4 kb genomic unit encompassing exons 7 and 8 in both species, indicating that after splitting of the two lineages, in the human mainly exon 8 was converted to a pseudoexon by splice site mutations. The structural features of cynDAZ reveal a more detailed model for the sequence of events leading to the present form of human DAZ. Thus, in a monkey species DAZ is present in a form more ancestral than that of the human. Studies on the immunolocalization of cynDAZ / DAZL1 in cynomolgus monkey testis revealed a biphasic expression pattern with proteins being detectable in A-pale to B-spermatogonia, late spermatocytes and spermatids, but not in early spermatocytes and late spermatids. In contrast, in the marmoset monkey, an animal lacking DAZ, DAZL1 protein was only expressed in late spermatocytes and early spermatids. These findings point to an additional function of cynDAZ / cynDAZL1 during spermato- genesis in the Old World monkey not needed in the New World monkey.
A family of 5 genes that evolved within the past 1.9 Myr in diploid wheat was characterized. The ancestral gene, ALP-A1, is on chromosome 1A and encodes an aci-reductone dioxygenase-like protein. The duplicated genes ALP-A2, ALP-A3, ALP-A4.1, and ALP-A4.2 acquired complete coding sequences but lost the original promoter. They are on chromosomes 4A, 2A, 6A and 6A, respectively, and evolved sequentially, the youngest duplicated gene always producing the next duplicate. It is shown that dispersed gene duplication rate consists of the primary rate (duplications of ancestral genes) and the secondary rate (duplications of genes that had been generated by recent duplications). The primary rate was 2.5 x 10(-3) gene(-1) Myr(-1) in diploid wheat. The secondary rate was 5.2 x 10(-2) gene(-1) Myr(-1) in the ALP family. The 20-fold acceleration of the secondary rate was caused by the insertion of the ALP-A2 gene into a novel type transposon. Only the ALP-A1 and ALP-A3 genes are transcribed. The transcription of ALP-A3 is directed by a promoter within a DNA fragment similar to a CACTA type of DNA transposons, making ALP-A3 a new gene. The ALP-A3 transcript is longer than that of the ALP-A1. The half-life of ALP duplicated genes was estimated to be 0.87 Myr. Strong purifying selection acting on the ancestral gene ALP-A1 was undiminished by the evolution of duplicated genes. The evolution of the ALP family shows that repeated elements facilitate both gene duplication and expression of duplicated genes and highlights their importance for the evolution of gene repertoire in large plant genomes.
Previously we found that minisatellite located on the 5'-flanking sequence far from the transcription start site of the human ABO blood group genes and containing four tandem repeats of a 43 base pair (bp) consensus sequence was an enhancer element for the transcription of the ABO genes. Concerning the number of tandem repeats in the minisatellite, there are at least three alleles: ABOU1*1, ABOU1*3, and ABOU1*4. Besides the variability of the minisatellite, another location of the 5'-flanking sequence has two alleles associated with the insertion of the 35 bp DNA segment: ABOU2*0 allele with an uneventful sequence and ABOU2*1 allele with the 35-bp insertion, respectively. Both of the DNA polymorphisms are closely associated with the common alleles of blood group ABO phenotypes. Namely, the 5'-flanking configuration consisting of the alleles ABOU1*1 and ABOU2*0 links up with the common A1 allele, whereas, the other 5'-flanking configuration consisting of the alleles ABOU1*4 and ABOU2*1 links up with common B and O alleles (abbreviated as 1-0-A1, 4-1-B and 4-1-O). In these linkages between three loci of alleles of 102 unrelated healthy individuals, two are not consistent with the rules described above. One is 3-1-O and the other is 4-1-A2. These findings suggest that the 3 or 4 times repeats of a 43 bp consensus sequence at ABOU1 locus and the 35 bp-insertion at ABOU2 locus found in 5'-flanking sequence of the B and O genes are incidental to the ABO gene evolution, subject to the ancestral A1 gene.
The major histocompatibility complex (MHC)-F class Ib locus shows a limited polymorphism, and the function of its mainly intracellular protein is not clear. We have identified human leucocyte antigen (HLA)-F orthologous DNA sequences in Pongidae in order to study the MHC-F gene evolution and its products' function. HLA-F orthologous cDNA transcripts are found in chimpanzee and in the new primate species studied (bonobo, gorilla and orangutan). Analyses of the predicted amino acid sequences and their comparison with other primate MHC-F proteins show that MHC-F may be a protein with a typical class I structure and that the key residues of the peptide-binding region (PBR) are highly conserved in MHC-F in all studied primates species. Thus, MHC-F conservation along the primate evolution suggests an important role in cellular physiology. It is possible that the MHC-F protein could be involved, together with MHC-G and MHC-E, in the natural killer (NK) cell activity regulation, although rhesus macaque does not express MHC-G and MHC-E orthologues. The evolutionary pathway of the six-base-pair deletion at exon 2 existing in some primates is put forward.
The genomic structure of the mouse 59-kDa keratin gene, a Type I intermediate filament (IF) gene is presented. A comparison of the organization of this gene with that of the human 67-kDa keratin, a Type II IF gene, and hamster vimentin, a Type III IF gene, suggests a common evolutionary origin for Type I, II, and III IF genes. Most introns in these three types of IF genes occur at similar positions within the region encoding sequences predicted to form coiled-coils, but do not delineate structural subdomains. Interestingly though, most of the introns interrupt at or near the beginning of the characteristic 7-residue (heptad) repeat of sequences which form the coiled-coil. These data suggest that the three types of IF genes arose from a common ancestor which may have been assembled from smaller units containing multiple heptad repeats. Subsequent duplication events may then have formed the three known alpha-helical types and each of their various members.
Most of a 9 kb region of the Drosophila genome containing genes for several cuticle proteins has been sequenced. Five cuticle-gene-like sequences have been identified and mapped. Amino acid sequences of four of the five major third instar cuticle proteins have been determined. These four sequences are identical with those predicted from the sequences of four of the five genes. Two cuticle genes are transcribed in one direction and two in the opposite direction. The fifth cuticle-like gene is judged to be a pseudogene because several features of its structure and the absence of detectable transcripts suggest it is nonfunctional. Sequence comparisons indicate that it arose by an unequal crossing-over event involving two closely related and adjacent cuticle genes. Each of the four cuticle genes contains a signal peptide coding sequence interrupted by a short intervening sequence (about 60 bp) at a conserved site. Conserved sequences occur in the 5' mRNA untranslated region, in the adjacent 35 bp of upstream flanking sequence and at -200 bp from the mRNA start position in each of the cuticle genes. We discuss the structure, organization and evolution of these cuticle genes as a model small gene family.
Overlapping cDNAs derived from the chicken alpha-fibrinogen mRNA have been sequenced, beginning from within the coding region for the signal peptide of this subunit and terminating within the poly(A) extension. The predicted size of chicken alpha-fibrinogen is 54,187 daltons, which is the smallest of any alpha chain reported; the oligopeptide repeats that characterize the central regions of the other alpha subunits were conspicuously absent. A further unexpected finding was the presence on the mRNA of a separate, long open reading frame (752 nucleotides), beginning 312 nucleotides downstream from the alpha-fibrinogen coding sequence and containing intron-like features near its 5' end. The protein sequence predicted from this second open reading frame lacks an initiating methionine but is homologous to the C-terminal regions of all known beta- and gamma-fibrinogens as well as the C termini of two nonfibrinogen proteins: cytotactin (tenascin), an extracellular matrix protein, and pT49, a putative protein specific to cytotoxic T cells. The intron-like features of the second open reading frame immediately precede the region of common homology, and the beginnings of the corresponding homologous segments in the beta- and gamma-fibrinogen sequences are marked by aligned intron positions. Based on these findings, it is proposed that fibrinogen gene evolution included a fusion of two distinct ancestral genes.
Publicly available protein sequences represent only a small fraction of the full catalog of genes encoded by the genomes of different plants, such as green algae, mosses, gymnosperms, and angiosperms. By contrast, an enormous amount of expressed sequence tags (ESTs) exists for a wide variety of plant species, representing a substantial part of all transcribed plant genes. Integrating protein and EST sequences in comparative and evolutionary analyses is not straightforward because of the heterogeneous nature of both types of sequence data. By combining information from publicly available EST and protein sequences for 32 different plant species, we identified more than 250,000 plant proteins organized in more than 12,000 gene families. Approximately 60% of the proteins are absent from current sequence databases but provide important new information about plant gene families. Analysis of the distribution of gene families over different plant species through phylogenetic profiling reveals interesting insights into plant gene evolution, and identifies species- and lineage-specific gene families, orphan genes, and conserved core genes across the green plant lineage. We counted a similar number of approximately 9,500 gene families in monocotyledonous and eudicotyledonous plants and found strong evidence for the existence of at least 33,700 genes in rice (Oryza sativa). Interestingly, the larger number of genes in rice compared to Arabidopsis (Arabidopsis thaliana) can partially be explained by a larger amount of species-specific single-copy genes and species-specific gene families. In addition, a majority of large gene families, typically containing more than 50 genes, are bigger in rice than Arabidopsis, whereas the opposite seems true for small gene families.
Comparison of the gene-expression profiles between adults of Drosophila melanogaster and Drosophila simulans has uncovered the evolution of genes that exhibit sex-dependent regulation. Approximately half the genes showed differences in expression between the species, and among these, approximately 83% involved a gain, loss, increase, decrease, or reversal of sex-biased expression. Most of the interspecific differences in messenger RNA abundance affect male-biased genes. Genes that differ in expression between the species showed functional clustering only if they were sex-biased. Our results suggest that sex-dependent selection may drive changes in expression of many of the most rapidly evolving genes in the Drosophila transcriptome.
Teleost fish, which roughly make up half of the extant vertebrate species, exhibit an amazing level of biodiversity affecting their morphology, ecology and behaviour as well as many other aspects of their biology. This huge variability makes fish extremely attractive for the study of many biological questions, particularly of those related to evolution. New insights gained from different teleost species and sequencing projects have recently revealed several peculiar features of fish genomes that might have played a role in fish evolution and speciation. There is now substantial evidence that a round of tetraploidization/rediploidization has taken place during the early evolution of the ray-finned fish lineage, and that hundreds of duplicate pairs generated by this event have been maintained over hundreds of millions of years of evolution. Differential loss or subfunction partitioning of such gene duplicates might have been involved in the generation of fish variability. In contrast to mammalian genomes, teleost genomes also contain multiple families of active transposable elements, which might have played a role in speciation by affecting hybrid sterility and viability. Finally, the amazing diversity of sex determination systems and the plasticity of sex chromosomes observed in teleost might have been involved in both pre- and postmating reproductive isolation. Comparison of data generated by current and future genome projects as well as complementary studies in other species will allow one to approach the molecular and evolutionary mechanisms underlying genome diversity in fish, and will certainly significantly contribute to our understanding of gene evolution and function in humans and other vertebrates.
Human alpha-N-acetylgalactosaminidase (alpha-GalNAc; EC 3.2.1.49), the lysosomal glycohydrolase that cleaves alpha-N-acetylgalactosaminyl moieties in glycoconjugates, is encoded by a gene localized to chromosome 22q13----qter. The deficient activity of this enzyme results in Schindler disease, an autosomal recessive disorder characterized by the increased urinary excretion of glycopeptides and oligosaccharides containing alpha-N-acetylgalactosaminyl moieties. Recently, the 3.6-kb full-length alpha-GalNAc cDNA sequence was isolated and found to have remarkable nucleotide and predicted amino acid homology (55.8 and 46.9%, respectively) with the human alpha-galactosidase A (alpha-Gal A) cDNA. To investigate the possible evolutionary relatedness of the two glycosidases, the alpha-GalNAc chromosomal gene was isolated and characterized. Screening of a human genomic DNA cosmid library resulted in the identification of a clone, gAGB-1, with an approximately 35-kb insert that contained the entire alpha-GalNAc gene. A single approximately 15-kb EcoRI fragment of gAGB-1, which contained the complete 3.6-kb cDNA sequence, was digested and the subcloned fragments were sequenced in both orientations. The 13,709-bp alpha-GalNAc gene had nine exons ranging from 95 to 2028 bp and intronic sequences of 304 to 2684 bp. All exon/intron junctions conformed to the GT/AG consensus rule. Analysis of 1.4 kb of 5' flanking sequence revealed three Sp1 and two CAAT-like promoter elements. This region was GC-rich (56%), but no HTF island was identified. The gene contained six Alu-repetitive elements, all in the reverse orientation. Comparison of the structural organization of the alpha-GalNAc and the alpha-Gal A genes revealed that all six alpha-Gal A introns were identically positioned in the homologous alpha-GalNAc exonic sequence. Two additional introns, 1 and 8, were identfied in the alpha-GalNAc gene. The predicted amino acid sequences of alpha-GalNAc exons 2 through 7 and those of corresponding alpha-Gal A exons 1 through 6 were 46.2 to 62.7% identical. In contrast, there was little, if any, similarity between the deduced amino acid sequences of alpha-Gal A exon 7 and alpha-GalNAc exons 8 and 9. The remarkable amino acid identity and the identical exonic interruption by six introns of the alpha-GalNAc and alpha-Gal A genes suggest that this region in both genes is evolutionarily related and arose through duplication and divergence from a common ancestral gene.
Multiple copies of a given ribosomal RNA gene family undergo concerted evolution such that sequences of all gene copies are virtually identical within a species although they diverge normally between species. In eukaryotes, gene conversion and unequal crossing over are the proposed mechanisms for concerted evolution of tandemly repeated sequences, whereas dispersed genes are homogenized by gene conversion. However, the homogenization mechanisms for multiple-copy, normally dispersed, prokaryotic rRNA genes are not well understood. Here we compared the sequences of multiple paralogous rRNA genes within a genome in 12 prokaryotic organisms that have multiple copies of the rRNA genes. Within a genome, putative sequence conversion tracts were found throughout the entire length of each individual rRNA genes and their immediate flanks. Individual conversion events convert only a short sequence tract, and the conversion partners can be any paralogous genes within the genome. Interestingly, the genic sequences undergo much slower divergence than their flanking sequences. Moreover, genomic context and operon organization do not affect rRNA gene homogenization. Thus, gene conversion underlies concerted evolution of bacterial rRNA genes, which normally occurs within genic sequences, and homogenization of flanking regions may result from co-conversion with the genic sequence.