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PubMed2004

Mobile gene cassettes: a fundamental resource for bacterial evolution.

Horizontal gene transfer increases genetic diversity in prokaryotes to a degree not allowed by the limitations of reproduction by binary fission. The integron/gene cassette system is one of the most recently characterized examples of a system that facilitates horizontal gene transfer. This system, discovered in the context of multidrug resistance, is recognized in a clinical context for its role in allowing pathogens to adapt to the widespread use of antibiotics. Recent studies suggest that gene cassettes are common and encode functions relevant to many adaptive traits. To estimate the diversity of mobile cassettes in a natural environment, a molecular technique was developed to provide representative distributions of cassette populations at points within a sampling area. Subsequently, statistical methods analogous to those used for calculating species diversity were employed to assess the diversity of gene cassettes within the sample area in addition to gaining an estimate of cassette pool size. Results indicated that the number of cassettes within a 5x10-m sample area was large and that the overall mobile cassette metagenome was likely to be orders of magnitude larger again. Accordingly, gene cassettes appear to be capable of mobilizing a significant genetic resource and consequently have a substantial impact on bacterial adaptability.

Adaptation, Physiological↗
PubMed1987

Structure, organization, and regulation of a hamster proline-rich protein gene. A multigene family.

Genomic DNA fragments bearing proline-rich protein (PRP) genes expressed specifically in hamster parotid glands have been isolated and characterized. Complete exonic sequences as well as intronic and a considerable portion of the flanking sequences are reported for a PRP gene, H29. H29 is interrupted by three intervening sequences, with consensus splice junctions, and it likely encodes the acidic hamster PRP Hp43a. Exceedingly high homology of the 5'-untranslated region and the sequence encoding the signal peptide is observed with other PRPs of all species studied. Significant homology was also detected among the repetitive sequences of the mature acidic PRPs from human, mouse, hamster, and rat. This conservation of the internal repeats of the PRPs suggested that proline-rich protein gene evolution involved intragenic duplication of internal repeats and gene duplication and conversion. Both hamster and mouse PRP genes (H29 and mouse proline-rich protein gene, respectively) share considerable sequence similarity in the 5'-flanking regions for about 100 base pairs upstream. The remainder of the upstream sequences were heterologous except for three oligonucleotide regions with 60-70% sequence conservation. These three regions are thought to be involved in the regulation of the tissue-specific PRP gene induction.

Amino Acids↗
PubMed2000

Comparative sequence analysis of the VHL tumor suppressor gene.

Comparative genome analysis may provide novel insights into gene evolution and function. To investigate the von Hippel-Lindau (VHL) disease tumor suppressor gene, we sequenced the VHL gene in seven primate species. Comparative analysis was performed for human, primate, and rodent VHL genes and for a putative Caenorhabditis elegans VHL homologue identified by database analysis. The VHL gene has two translation initiation sites (at codons 1 and 54); however, the relative importance of the full-length translation product (pVHL30) and that translated from the second internal translation initiation site (pVHL19) is unclear. The N-terminal sequence of pVHL30 contains eight copies of a GXEEX acidic repeat motif in human and higher primates, but only three copies were present in the marmoset, and only one copy was present in rodent VHL genes. Evolutionary analysis suggested that the N-terminal repetitive sequence in pVHL30 was of less functional importance than those regions present in both pVHL30 and pVHL19. The VHL gene product is reported to form complexes with various proteins including elongin B, elongin C, VBP-1, fibronectin, Spl, CUL2, and HIF-1. Although most of the regions in pVHL that had been implicated in binding specific proteins demonstrated evolutionary conservation, the carboxy-terminal putative VBP-1 binding site was less well conserved, suggesting that VBP-1 binding may have less functional significance. Although an amino acid substitution (K171T) close to the pVHL elongin binding region was found in baboon, analysis of the structure of human pVHL suggested that this substitution would not interfere with pVHL/elongin C interaction. In general, there was a good correlation between the pVHL domains that demonstrated most evolutionary conservation and those that were most frequently mutated in tumors. Analysis of human/C. elegans conservation and human germline and somatic mutation patterns identified a highly conserved mutation cluster region between codons 74 and 90. However, this region is likely to be important for the structural integrity of pVHL rather than representing an additional protein binding domain.

Amino Acid Sequence↗
PubMed2003

Genomic organization of ZP domain containing egg envelope genes in medaka (Oryzias latipes).

To provide insights into the diversity of egg envelope genes in teleosts, we determined the genomic organization and the map position of the medaka egg envelope genes expressed either in the oocytes or in the liver. There seems to be five classes of ZP domain containing egg envelope genes in vertebrates: zpa, zpax, zpb, zpc, and zpd. zpa, zpax, and zpb are much closely related than zpc. There is an expanded family of teleost-specific zpc genes. The duplication of the possible zpb/zpc cluster happened in the teleost lineage may be a cause of liver-specific ZP gene evolution in teleosts. The inconsistent presence of a repetitive amino acid domain among teleost zpb and zpc gene products suggests rapid evolution of this domain. In addition, relative abundance of E-boxes in putative promoters of medaka oocyte-specific ZP genes suggests their regulation by basic helix-loop-helix transcription factors, particularly by FIGalpha.

Amino Acid Sequence↗
PubMed1992

Genetic regulation of secondary metabolic pathways in Streptomyces.

Streptomyces species are (along with the fungi) the best-known antibiotic-producing organisms. Often, they make several different antibiotics. The biosynthesis of each antibiotic is encoded by a complex gene cluster that usually also contains regulatory and resistance genes. Typically, there may be more than one such pathway-specific regulatory gene per cluster. Both activator and repressor genes are known. Some of the regulatory genes for different pathways are related. In S. coelicolor, expression of several such biosynthetic gene clusters also depends on at least 11 globally acting genes, at least one of which is involved in the translation of a rare codon (UUA). A protein phosphorylation cascade also seems to be involved. Gene clusters closely similar to those for the biosynthesis of aromatic polyketide antibiotics determine spore pigment in some species. These genes show different regulation from antibiotic production genes. The evolution of gene clusters for polyketide antibiotics, and the possible adaptive benefits of secondary metabolism, are discussed.

Anti-Bacterial Agents↗
PubMed2000

Molecular cloning, characterization and evolution of the gene encoding a new group of short-chain alpha-neurotoxins in an Australian elapid, Pseudonaja textilis.

The structure and organization of five genes responsible for the synthesis of six isoforms of short-chain alpha-neurotoxins in Pseudonaja textilis venom are reported in this paper. This also forms the first report which describes the synthesis of two neurotoxin mRNA variants from one of these genes (Pt-sntx1) as a result of alternative splicing. Each gene consists of three exons which are separated by two introns and each has a functional promoter. The promoter activity was confirmed by both CAT assay and Real-Time PCR. A transcription initiation site, two putative TATA boxes, one CCAAT box and the transcription factor binding consensus sites for AP-1, GATA-2, c/EBPb were identified in the 5' non-coding region of each gene. Phylogenetic analysis showed that these five genes from P. textilis constituted a distinct group which has evolved by gene duplication followed by accelerated evolution from an ancestral gene.

Alternative Splicing↗
PubMed1998

Molecular evolution of an imprinted gene: repeatability of patterns of evolution within the mammalian insulin-like growth factor type II receptor.

The repeatability of patterns of variation in Ka/Ks and Ks is expected if such patterns are the result of deterministic forces. We have contrasted the molecular evolution of the mammalian insulin-like growth factor type II receptor (Igf2r) in the mouse-rat comparison with that in the human-cow comparison. In so doing, we investigate explanations for both the evolution of genomic imprinting and for Ks variation (and hence putatively for mutation rate evolution). Previous analysis of Igf2r, in the mouse-rat comparison, found Ka/Ks patterns that were suggested to be contrary to those expected under the conflict theory of imprinting. We find that Ka/Ks variation is repeatable and hence confirm these patterns. However, we also find that the molecular evolution of Igf2r signal sequences suggests that positive selection, and hence conflict, may be affecting this region. The variation in Ks across Igf2r is also repeatable. To the best of our knowledge this is the first demonstration of such repeatability. We consider three explanations for the variation in Ks across the gene: (1) that it is the result of mutational biases, (2) that it is the result of selection on the mutation rate, and (3) that it is the product of selection on codon usage. Explanations 2 and 3 predict a Ka-Ks correlation, which is not found. Explanation 3 also predicts a negative correlation between codon bias and Ks, which is also not found. However, in support of explanation 1 we do find that in rodents the rate of silent C --> T mutations at CpG sites does covary with Ks, suggesting that methylation-induced mutational patterns can explain some of the variation in Ks. We find evidence to suggest that this CpG effect is due to both variation in CpG density, and to variation in the frequency with which CpGs mutate. Interestingly, however, a GC4 analysis shows no covariance with Ks, suggesting that to eliminate methyl-associated effects CpG rates themselves must be analyzed. These results suggest that, in contrast to previous studies of intragenic variation, Ks patterns are not simply caused by the same forces responsible for Ka/Ks correlations.

Animals↗
PubMed2006

Tspy is nonfunctional in the Mongolian gerbil but functional in the Syrian hamster.

The TSPY gene is conserved in placental mammals and encodes the testis-specific protein, Y encoded. Within the testis, TSPY expression is restricted to germ cells, and it is assumed that TSPY plays a role in the proliferation of germ cells. Since it was first discovered in humans, TSPY orthologous gene families have been subsequently characterized in many mammalian lineages. In contrast to the situation in cattle and primates, in which TSPY is organized in a moderately repetitive cluster, including functional members and pseudogenes, a peculiar situation is observed in rodents, in which Tspy has been become low or single copy and degenerated to a pseudogene in some species of the subgenus Mus. We have extended this approach and investigated Tspy gene evolution in the Syrian hamster (Mesocricetus auratus) and the Mongolian gerbil (Meriones unguiculatus). Whereas the Syrian hamster Tspy is functionally conserved, organized in multiple copies, and expressed only in testis, the closely related Mongolian gerbil possesses a single-copy pseudogene that is unable to generate a functional transcript. Thus, the Tspy locus has degenerated at least twice at different points of rodent evolution, strongly supporting the hypothesis that the decay of Y-chromosomal genes is an intrinsic evolutionary process. TSPY is the first example of a Y-chromosomal tandem repetitive gene whose decay could be studied in two independent mammalian lineages.

Animals↗
PubMed1984

Sea urchin actin gene subtypes. Gene number, linkage and evolution.

The actin gene family of the sea urchin Strongylocentrotus purpuratus was analyzed by the genome blot method, using subcloned probes specific to the 3' terminal non-translated actin gene sequence, intervening sequence and coding region probes. We define an actin gene subtype as that gene or set of genes displaying homology with a given 3' terminal sequence probe, when hybridized at 55 degrees C, 0.75 M-Na+. By determining the often polymorphic restriction fragment band pattern displayed in genome blots by each probe, all, or almost all of the actin genes in this species could be classified. Our evidence shows that the S. purpuratus genome probably contains seven to eight actin genes, and these can be assigned to four subtypes. Studies of the expression of the genes (Shott et al., 1983) show that the actin genes of three of these subtypes code for cytoskeletal actins (Cy), while the fourth gives rise to a muscle-specific actin (M). We denote the array of S. purpuratus actin genes indicated by our data as follows. There is a single CyI actin gene, two or possibly three CyII genes (CyIIa, CyIIb, and possibly CyIIc), three CyIII actin genes (CyIIIa, CyIIIb, CyIIIc), and a single M actin gene. Comparative studies were carried out on the actin gene families of five other sea urchin species. At least the CyIIa and CyIIb genes are also linked in the Strongylocentrotus franciscanus genome, and this species also has a CyI gene, an M actin gene and at least two CyIII actin genes. It is not clear whether it also possesses a CyIIc actin gene, or a CyIIIc actin gene. The genome of a more closely related congener, Strongylocentrotus dröbachiensis, includes 3' terminal sequences suggesting the presence of a CyIIc gene. In S. franciscanus and S. dröbachiensis the first intron of the CyI gene has remained homologous with intron sequences of both the CyIIa and CyIIb genes, indicating a common origin of these three linked cytoskeletal actin genes. Of the four S. purpuratus 3' terminal subtype probe sequences only the CyI 3' terminal sequence has been conserved sufficiently during evolution to permit detection outside of the genus Strongylocentrotus. An unexpected observation was that a sequence found only in the 3' untranslated region of the CyII actin gene in the DNA of S. dröbachiensis and S. purpuratus is represented as a large family of interspersed repeat sequences in the genome of S. franciscanus.

Actins↗
PubMed1984

The gene encoding the beta-subunit of rat luteinizing hormone. Analysis of gene structure and evolution of nucleotide sequence.

The nucleotide sequence of the gene encoding the beta-subunit of rat luteinizing hormone (LH beta) has been determined from a genomic DNA fragment cloned in lambda phage Charon 4A. Blot hybridization of restriction enzyme digests of rat genomic DNA indicates that the gene is present in a single copy. The transcriptional unit is 0.98 kilobase in size and contains three exons interrupted by two introns of 245 and 225 base pairs (bp). The locations of the exon/intron junctions at amino acid codons -16/-15 and +41/+42 have been conserved between the rat LH beta gene and the related genes, human LH beta and human chorionic gonadotropin beta. Using S1 nuclease mapping and oligonucleotide-primed reverse transcription of ovariectomized rat pituitary mRNA, the start of transcription was determined to be 7 bp upstream from the start of translation. Characteristic promoter elements are present in the 5'-flanking region of the gene, including the Goldberg-Hogness sequence, TATAAA, 31 bp, and the consensus CAAT box sequence, 167 bp upstream from the start of transcription, respectively. Within the proximal 200 bp flanking the 5'-region of the transcriptional unit, there is strong homology between the rat and human LH beta genes, suggesting that these regions include sequences which may be important for regulation of gene expression. Isolation and characterization of the rat LH beta gene further defines the evolution of glycoprotein hormone genes and will facilitate the study of cellular and molecular mechanisms which regulate LH beta gene expression.

Amino Acid Sequence↗
PubMed1987

On the evolution of ribosomal RNA.

Despite the availability of a rapidly growing ribosomal RNA database that now includes organisms in all three primary lines of descent (eubacteria, archaebacteria, and eukaryotes), theoretical treatment of the evolution of the ribosomal RNAs has lagged behind that of the protein genes. In this paper a theory is developed that applies current views of protein gene evolution to the ribosomal RNAs. The major topics addressed are the variability in size, gene arrangement, and processing of the rRNAs among the three primary lines of descent. Among the conclusions are that the rRNAs of eukaryotes retain some primitive features that were probably present in the rRNAs of the earliest cell (the progenote) and that the genes coding for the three major rRNA species were probably originally unlinked.

Animals↗
PubMed2000

The evolution of duplicated genes considering protein stability constraints.

We model the evolution of duplicated genes by assuming that the gene's protein message, if transcribed and translated, must form a stable, folded structure. We observe the change in protein structure over time in an evolving population of lattice model proteins. We find that selection of stable proteins conserves the original structure if the structure is highly designable, that is, if a large fraction of all foldable sequences form that structure. This effect implies the relative number of pseudogenes can be less than previously predicted with neutral evolution models. The data also suggests a reason for lower than expected ratios of non-synonymous to synonymous substitutions in pseudogenes.

Computer Simulation↗
PubMed2006

Paleopolyploidy and gene duplication in soybean and other legumes.

Two of the most important observations from whole-genome sequences have been the high rate of gene birth and death and the prevalence of large-scale duplication events, including polyploidy. There is also a growing appreciation that polyploidy is more than the sum of the gene duplications it creates, in part because polyploidy duplicates the members of entire regulatory networks. Thus, it may be important to distinguish paralogs that are produced by individual gene duplications from the homoeologous sequences produced by (allo)polyploidy. This is not a simple task, for several reasons, including the chromosomally cryptic nature of many duplications and the variable rates of gene evolution. Recent progress has been made in understanding patterns of gene and genome duplication in the legume family, specifically in soybean.

Biological Evolution↗
PubMed2005

Pack-MULEs: theft on a massive scale.

It has been known for some time that plant transposons can capture and mobilize cellular genes. Recent work by Jiang and coworkers((1)) has revealed that this process has happened on a massive scale. They found that portions of more than 1000 genes in rice have been captured and mobilized by members of the MULE family of transposons. In rice, and perhaps other plants as well, it appears that thousands of genes and portions of genes have been duplicated, transposed and rearranged. These results have fascinating implications for our understanding of the mode and tempo of gene evolution in plants.

Biological Evolution↗
PubMed1994

The alphaviruses: gene expression, replication, and evolution.

The alphaviruses are a genus of 26 enveloped viruses that cause disease in humans and domestic animals. Mosquitoes or other hematophagous arthropods serve as vectors for these viruses. The complete sequences of the +/- 11.7-kb plus-strand RNA genomes of eight alphaviruses have been determined, and partial sequences are known for several others; this has made possible evolutionary comparisons between different alphaviruses as well as comparisons of this group of viruses with other animal and plant viruses. Full-length cDNA clones from which infectious RNA can be recovered have been constructed for four alphaviruses; these clones have facilitated many molecular genetic studies as well as the development of these viruses as expression vectors. From these and studies involving biochemical approaches, many details of the replication cycle of the alphaviruses are known. The interactions of the viruses with host cells and host organisms have been exclusively studied, and the molecular basis of virulence and recovery from viral infection have been addressed in a large number of recent papers. The structure of the viruses has been determined to about 2.5 nm, making them the best-characterized enveloped virus to date. Because of the wealth of data that has appeared, these viruses represent a well-characterized system that tell us much about the evolution of RNA viruses, their replication, and their interactions with their hosts. This review summarizes our current knowledge of this group of viruses.

Alphavirus↗
PubMed2006

Gene nutrient interactions and evolution.

Nutritional requirements are not the same for all individuals. While there is generally a common requirement for the types of nutrients needed for survival, the quantities needed vary. In several instances, the differences in nutrient requirements can be attributed to specific genetic differences among individuals. When higher nutrient needs associated with certain genotypes are not met, there will be selection against those genotypes in the population. When these needs are met, the selection against such genotypes will be lifted and the alleles that confer high nutrient requirements can persist in the population. In cases where these alleles confer some selective advantage, high levels of the required nutrient can actually lead to an expanded frequency of those alleles in a population. In such cases, nutrient availability can provide a selective pressure that drives genotypic shifts in a population. Some of the data demonstrating the potential of nutrient levels to affect genetic evolution of a population are reviewed here.

Alleles↗