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PubMed1995

Localization of the alpha 7 integrin gene (ITGA7) on human chromosome 12q13: clustering of integrin and Hox genes implies parallel evolution of these gene families.

Expression of the alpha 7 integrin gene (ITGA7) is developmentally regulated during the formation of skeletal muscle. Increased levels of expression and production of isoforms containing different cytoplasmic and extracellular domains accompany myogenesis. To determine whether a single or multiple alpha 7 genes underlie the structural diversity in this alpha chain that accompanies development, we have examined the rat and human genomes by Southern blotting and in situ hybridization. Our results demonstrate that there is only one alpha 7 gene in both the rat and the human genomes. In the human, ITGA7 is present on chromosome 12q13. Phylogenetic analysis of the integrin alpha chain sequences suggests that the early integrin genes evolved in two pathways to form the I-integrins and the non-I-integrins. The I-integrin alpha chains contain an additional sequence of approximately 180 amino acids and arose as a result of an early insertion into the non-I-gene. The I-chain subfamily further evolved by duplications within the same chromosome. The non-I-integrin alpha chain genes are localized in clusters on chromosomes 2, 12, and 17, and this closely coincides with the localization of the human homeobox gene clusters. Non-I-integrin alpha chain genes appear to have evolved in parallel and in proximity to the Hox clusters. Thus, the Hox genes that underlie the design of body structure and the Integrin genes that underlie informed cell-cell and cell-matrix interactions appear to have evolved in parallel and coordinate fashions.

Amino Acid Sequence↗
PubMed2000

High-resolution FISH mapping of the rat alpha2u-globulin multigene family.

The rat alpha2u-globulins are a group of similar proteins that are encoded by a family of approximately 20 genes located a single locus of < or =880 kbp on Chromosome (Chr) 5q. Individual members of this gene family demonstrate complex tissue, hormonal, and developmental expression patterns despite a high degree of sequence similarity among the members and consequently provide an interesting system for studying the evolution of differential gene expression. Hybridization analysis indicated that gene classes, similar to those identified at the homologous MUP locus in the mouse, do not exist within the rat alpha2u-globulin locus. Furthermore, cross-hybridization analysis revealed the presence of conserved sequences in the 5' and 3' regions flanking the alpha2u-globulin genes, some of which were present in an inverted orientation. We have used high-resolution fiber FISH to examine the structural organization of the alpha2u-globulin locus, and found the genes to be arranged as an array of both direct and inverted repeats. The organization of the rat alpha2u-globulin genes differs from the MUP genes and suggests different evolutionary events have reorganized these homologous sets of genes.

Alpha-Globulins↗
PubMed2005

Mitochondrial voltage-dependent anion channel gene family in Drosophila melanogaster: complex patterns of evolution, genomic organization, and developmental expression.

Voltage-dependent anion channels (VDACs), also known as mitochondrial porins, are a family of small pore-forming proteins of the mitochondrial outer membrane found in all eukaryotes. VDACs play important roles in the regulated flux of metabolites between the cytosolic and mitochondrial compartments, energy metabolism, and apoptosis. Annotation of the genome sequence of Drosophila melanogaster revealed three genes (CG17137, CG31722-A, and CG31722-B) with homology to porin, the previously described Drosophila VDAC. Molecular analysis reveals a complex pattern of organization and expression. The genomic organization of these four genes and sequence comparisons with other insect VDAC homologs indicate that this gene family evolved through a mechanism of duplication and divergence from an ancestral VDAC gene during the radiation of the genus Drosophila. CG17137, CG31722-A, and CG31722-B are expressed in a male-specific pattern on both transcriptional and translational levels, while porin is equally expressed in both male and female flies. Additionally, CG31722-A and CG31722-B are expressed as a dicistronic transcript. Western blot analysis and immunofluorescence microscopy confirm that these proteins localize to the mitochondrion. Further expression analysis showed that CG17137 and CG31722-B are abundant in testes, while porin is ubiquitously expressed. While porin, CG17137, and CG31722-B are expressed to different degrees during embryogenesis, all of these proteins are dramatically reduced relative to cytochrome c content during larvogenesis. These studies illustrate a complex genomic organization and spatiotemporal pattern of expression for Drosophila VDACs as well as an evolutionary history consistent with either a partitioning of VDAC functions or an acquisition of novel functions among isoforms.

Amino Acid Sequence↗
PubMed2001

Molecular cloning of cDNA encoding thyroid stimulating hormone beta subunit of bighead carp Aristichthys nobilis and regulation of its gene expression.

The complementary DNA (cDNA) encoding pituitary thyroid stimulating hormone beta subunit (TSH-beta) of bighead carp was cloned and regulation of its gene expression was investigated for understanding phylogenetic divergence and evolution of TSH molecule. The cDNA was obtained from bighead carp pituitary total RNA by reverse transcription and polymerase chain reaction. Oligonucleotide primers were designed from the sequence of common carp. The full length sequence was then obtained by 3' and 5' rapid amplification of cDNA ends (RACE). The full-length sequence consisting of 3' and 5' untranslated regions was 585 bp long. The predicted amino acid sequence consisted of a signal peptide of 19 amino acid residues and a mature TSH beta subunit protein of 131 residues. The coding sequences of the cDNAs showed variable percentage homologies with those of other teleosts and vertebrate species. The predicted amino acid sequence shared 71% identity with rainbow trout and salmon, 90% with goldfish, 50% with eel and 94% with common carp in the mature protein region. The percentages of identity in the same region in comparison with bovine, porcine, rat, mouse, human and chicken were only 39, 42, 41, 40, 45 and 46%, respectively. TSH beta mRNA expression was found only in the pituitary tissue out of other tissues tested as testis, muscle, brain and heart. For the first time, thyrotropin releasing hormone (TRH) and thyroxine (T4) effects on pituitary TSH mRNA expression were tested in teleosts under in vitro conditions. TRH treatment on pituitary cells increased TSH beta mRNA level, while T4 treatment decreased TSH beta mRNA level. The present study provides a direct evidence, for the first time that TRH directly upregulates TSH beta gene expression in teleosts.

Amino Acid Sequence↗
PubMed2000

Expression and evolution of the Drosophila attacin/diptericin gene family.

We describe the genes for three new glycine-rich antimicrobial peptides in Drosophila, two attacins (AttC and AttD) and one diptericin (DptB). Their structures support the proposal that these glycine-rich antimicrobial peptides evolved from a common ancestor and are probably also related to proline-rich peptides such as drosocin. AttC is similar to the nearby AttA and AttB genes. AttD is more divergent and located on a different chromosome. Intriguingly, AttD may encode an intracellular attacin. DptB is linked in tandem to the closely related Diptericin. However, the DptB gene product contains a furin-like cleavage site and may be processed in an attacin-like fashion. All attacin and diptericin genes are induced after bacterial challenge. This induction is reduced in imd mutants, and unexpectedly also in Tl(-) mutants. The 18w mutation particularly affects the induction of AttC, which may be a useful marker for 18w signaling.

Amino Acid Sequence↗
PubMed1992

Evolution of the expression of the Gld gene in the reproductive tract of Drosophila.

During the preadult development of Drosophila melanogaster, the GLD (glucose dehydrogenase) gene (Gld) is expressed in a variety of tissues, including the immature reproductive tract. At the adult stage the expression of Gld becomes largely restricted to the reproductive tract of males and females. We examined the expression of GLD in the adult reproductive tract of 50 species in the genus Drosophila, as well as in those of a few representative species from four other closely related genera. GLD exhibits considerable organ-specific diversity in the reproductive tract of males and females. Among these species, five male GLD phenotypes and six female GLD phenotypes were found. In contrast, the preadult expression of GLD in representative species from each distinct adult pattern type was determined and found to be highly conserved in both the immature reproductive tract and non-reproductive organs. Moreover, the set of reproductive organs that express GLD during preadult development is equivalent to the sum of the five male and six female adult GLD phenotypes. To initially define the contribution of cis- versus trans-acting factors responsible for differences in adult GLD expression between two of these species--D. melanogaster and D. pseudoobscura--we transferred the D. pseudoobscura Gld to the genome of D. melanogaster and investigated its expression. GLD expression patterns of these transformants displayed characteristics that are unique to both species, suggesting the presence of both cis- and trans-acting differences between these two species.

Age Factors↗
PubMed1985

Evolution and expression of the transplantation antigen gene family.

We have cloned 26 different class I genes that are located in the major histocompatibility complex of the C57BL/10 mouse. Two of the three class I genes found in the H-2 complex encode the H-2Kb and H-2Db antigens; the other 23 class I genes map to the adjacent Tla complex. We have grouped the cosmids containing these genes into three clusters: one cluster links the H-2K and I-A regions, one cluster links the H-2D and Qa-2 regions, and the final cluster maps to the TL region. The class I gene organizations in the Qa-2 and TL regions of the C57BL/10 and BALB/c mice are generally similar, but there are several polymorphic segments. The Qa-2 region of both mice seems to have evolved by the duplication of gene pairs; furthermore, the H-2K region may have been generated by the translocation of a gene pair from the Qa-2 region. We have evidence that several of the genes in the Qa-2 region are expressed.

Animals↗
PubMed2003

Understanding mechanisms of novel gene expression in polyploids.

Polyploidy has long been recognized as a prominent force shaping the evolution of eukaryotes, especially flowering plants. New phenotypes often arise with polyploid formation and can contribute to the success of polyploids in nature or their selection for use in agriculture. Although the causes of novel variation in polyploids are not well understood, they could involve changes in gene expression through increased variation in dosage-regulated gene expression, altered regulatory interactions, and rapid genetic and epigenetic changes. New research approaches are being used to study these mechanisms and the results should provide a more complete understanding of polyploidy.

Biological Evolution↗
PubMed2006

A new experimental approach for studying bacterial genomic island evolution identifies island genes with bacterial host-specific expression patterns.

BACKGROUND: Genomic islands are regions of bacterial genomes that have been acquired by horizontal transfer and often contain blocks of genes that function together for specific processes. Recently, it has become clear that the impact of genomic islands on the evolution of different bacterial species is significant and represents a major force in establishing bacterial genomic variation. However, the study of genomic island evolution has been mostly performed at the sequence level using computer software or hybridization analysis to compare different bacterial genomic sequences. We describe here a novel experimental approach to study the evolution of species-specific bacterial genomic islands that identifies island genes that have evolved in such a way that they are differentially-expressed depending on the bacterial host background into which they are transferred. RESULTS: We demonstrate this approach by using a "test" genomic island that we have cloned from the Salmonella typhimurium genome (island 4305) and transferred to a range of Gram negative bacterial hosts of differing evolutionary relationships to S. typhimurium. Systematic analysis of the expression of the island genes in the different hosts compared to proper controls allowed identification of genes with genera-specific expression patterns. The data from the analysis can be arranged in a matrix to give an expression "array" of the island genes in the different bacterial backgrounds. A conserved 19-bp DNA site was found upstream of at least two of the differentially-expressed island genes. To our knowledge, this is the first systematic analysis of horizontally-transferred genomic island gene expression in a broad range of Gram negative hosts. We also present evidence in this study that the IS200 element found in island 4305 in S. typhimurium strain LT2 was inserted after the island had already been acquired by the S. typhimurium lineage and that this element is likely not involved in the integration or excision of island 4305. CONCLUSION: The "clone-and-transfer" approach of evolutionary study identifies genes whose expression patterns indicate the existence of genera-specific regulatory mechanisms that influence the expression of horizontally-transferred DNA sections. The results provide key information that can be used to facilitate the identification of these regulatory mechanisms.

Bacteria↗
PubMed2007

A combined computational and experimental analysis of two families of snoRNA genes from Caenorhabditis elegans, revealing the expression and evolution pattern of snoRNAs in nematodes.

Small nucleolar RNAs (snoRNAs) are an abundant group of noncoding RNAs mainly involved in the posttranscriptional modifications of rRNAs in eukaryotes. Prior to this study, only 28 snoRNA genes had been identified from Caenorhabditis elegans, indicating that most snoRNA genes are hidden in the worm genome, which represents a simple multicellular metazoan. In this study, a genome-wide analysis of the two major families of snoRNA genes in C. elegans was performed using the snoscan and snoGPS programs incorporating comparative genome analyses. Seventy gene variants, including 36 box C/D and 34 box H/ACA snoRNA genes, were identified, of which 50 are novel. Two families of snoRNAs showed a characteristic genomic organization. Notably, 6 box C/D snoRNA genes were located in the antisense orientation of introns. In contrast to insect and mammal, the distances between many intronic snoRNAs and 3' splice sites of introns were less than 50 nt in the worm, an unexpected finding as intron-encoded snoRNAs in C. elegans are supposed to be expressed in a splicing-dependent pathway. Interestingly, a canonical H/ACA snoRNA, PsiCeU5-48, was revealed to be partially homologous to small Cajal body-specific RNA (scaRNA) U85 and U89 in fly and human, indicating a possible evolutionary relationship between snoRNAs and scaRNAs.

Animals↗
PubMed1999

Control of genes by mammalian retroposons.

Available data on possible genetic impacts of mammalian retroposons are reviewed. Most important is the growing number of established examples showing the involvement of retroposons in modulation of expression of protein-coding genes transcribed by RNA polymerase II (Pol II). Retroposons contain conserved blocks of nucleotide sequence for binding of some important Pol II transcription factors as well as sequences involved in regulation of stability of mRNA. Moreover, these mobile genes provide short regions of sequence homology for illegitimate recombinations, leading to diverse genome rearrangements during evolution. Therefore, mammalian retroposons representing a significant fraction of noncoding DNA cannot be considered at present as junk DNA but as important genetic symbionts driving the evolution of regulatory networks controlling gene expression.

Alu Elements↗
PubMed2003

Bacterial evolution through the selective loss of beneficial Genes. Trade-offs in expression involving two loci.

The loss of preexisting genes or gene activities during evolution is a major mechanism of ecological specialization. Evolutionary processes that can account for gene loss or inactivation have so far been restricted to one of two mechanisms: direct selection for the loss of gene activities that are disadvantageous under the conditions of selection (i.e., antagonistic pleiotropy) and selection-independent genetic drift of neutral (or nearly neutral) mutations (i.e., mutation accumulation). In this study we demonstrate with an evolved strain of Escherichia coli that a third, distinct mechanism exists by which gene activities can be lost. This selection-dependent mechanism involves the expropriation of one gene's upstream regulatory element by a second gene via a homologous recombination event. Resulting from this genetic exchange is the activation of the second gene and a concomitant inactivation of the first gene. This gene-for-gene expression tradeoff provides a net fitness gain, even if the forfeited activity of the first gene can play a positive role in fitness under the conditions of selection.

Adaptation, Physiological↗
PubMed2005

Expression divergence between duplicate genes.

A general picture of the role of expression divergence in the evolution of duplicate genes is emerging, thanks to the availability of completely sequenced genomes and functional genomic data, such as microarray data. It is now clear that expression divergence, regulatory-motif divergence and coding-sequence divergence all increase with the age of duplicate genes, although their exact interrelationships remain to be determined. It is also clear that gene duplication increases expression diversity and enables tissue or developmental specialization to evolve. However, the relative roles of subfunctionalization and neofunctionalization in the retention of duplicate genes remain to be clarified, especially for higher eukaryotes. In addition, the relationship between gene duplication and evolution of transcriptional regulatory networks is largely unexplored.

Evolution, Molecular↗
PubMed1996

Evolutionary strategies for the elucidation of cis and trans factors that regulate the developmental switching programs of the beta-like globin genes.

We describe three strategies for the identification of specific cis and trans factors that regulate globin gene expression, all three of which are based on the evolution of the globin genes and their expression patterns. The first approach, phylogenetic footprinting, relies on a search for sequence similarities and is designed to elucidate the factors that control those expression patterns which are shared by orthologous globin genes of all eutherian mammals (e.g., the expression of the epsilon globin genes in the embryonic yolk sac and its repression in fetal and adult hematopoietic tissues). The second approach, differential phylogenetic footprinting, relies on a search for sequence differences. This approach may be of value in identifying the mechanisms underlying the generation of novel expression patterns in specific lineages (e.g., the expression of gamma as a fetal gene in the simian primates in contrast with the embryonic expression of gamma in all other mammals). Finally, motif-based phylogenetic analysis takes into consideration the fact that many transcription factors are quite flexible in the recognition of their cognate sites. The approach allows the detection of functionally conserved binding sites despite their sequence variation.

Adult↗
PubMed2002

Abundant raw material for cis-regulatory evolution in humans.

Changes in gene expression and regulation--due in particular to the evolution of cis-regulatory DNA sequences--may underlie many evolutionary changes in phenotypes, yet little is known about the distribution of such variation in populations. We present in this study the first survey of experimentally validated functional cis-regulatory polymorphism. These data are derived from more than 140 polymorphisms involved in the regulation of 107 genes in Homo sapiens, the eukaryote species with the most available data. We find that functional cis-regulatory variation is widespread in the human genome and that the consequent variation in gene expression is twofold or greater for 63% of the genes surveyed. Transcription factor-DNA interactions are highly polymorphic, and regulatory interactions have been gained and lost within human populations. On average, humans are heterozygous at more functional cis-regulatory sites (>16,000) than at amino acid positions (<13,000), in part because of an overrepresentation among the former in multiallelic tandem repeat variation, especially (AC)(n) dinucleotide microsatellites. The role of microsatellites in gene expression variation may provide a larger store of heritable phenotypic variation, and a more rapid mutational input of such variation, than has been realized. Finally, we outline the distinctive consequences of cis-regulatory variation for the genotype-phenotype relationship, including ubiquitous epistasis and genotype-by-environment interactions, as well as underappreciated modes of pleiotropy and overdominance. Ordinary small-scale mutations contribute to pervasive variation in transcription rates and consequently to patterns of human phenotypic variation.

Evolution, Molecular↗
PubMed2005

Expression of floral MADS-box genes in basal angiosperms: implications for the evolution of floral regulators.

The ABC model of floral organ identity is based on studies of Arabidopsis and Antirrhinum, both of which are highly derived eudicots. Most of the genes required for the ABC functions in Arabidopsis and Antirrhinum are members of the MADS-box gene family, and their orthologs are present in all major angiosperm lineages. Although the eudicots comprise 75% of all angiosperms, most of the diversity in arrangement and number of floral parts is actually found among basal angiosperm lineages, for which little is known about the genes that control floral development. To investigate the conservation and divergence of expression patterns of floral MADS-box genes in basal angiosperms relative to eudicot model systems, we isolated several floral MADS-box genes and examined their expression patterns in representative species, including Amborella (Amborellaceae), Nuphar (Nymphaeaceae) and Illicium (Austrobaileyales), the successive sister groups to all other extant angiosperms, plus Magnolia and Asimina, members of the large magnoliid clade. Our results from multiple methods (relative-quantitative RT-PCR, real-time PCR and RNA in situ hybridization) revealed that expression patterns of floral MADS-box genes in basal angiosperms are broader than those of their counterparts in eudicots and monocots. In particular, (i) AP1 homologs are generally expressed in all floral organs and leaves, (ii) AP3/PI homologs are generally expressed in all floral organs and (iii) AG homologs are expressed in stamens and carpels of most basal angiosperms, in agreement with the expectations of the ABC model; however, an AG homolog is also expressed in the tepals of Illicium. The broader range of strong expression of AP3/PI homologs is inferred to be the ancestral pattern for all angiosperms and is also consistent with the gradual morphological intergradations often observed between adjacent floral organs in basal angiosperms.

Evolution, Molecular↗
PubMedDate not supplied

[Alzheimer's disease and brain evolution: is Alzheimer's disease an example of antagonistic pleiotropy?].

INTRODUCTION: Alzheimer's disease (AD) appears to be exclusive to our species. This suggests a relationship between the disease and genetic, functional and structural changes that have taken place throughout the evolution of the human brain. DEVELOPMENT: The expression of genes linked to neurotransmission, neuroplasticity, axonal transport, aerobic metabolism and neuroprotection seems to have increased within the human cerebral cortex and such phenomena represent adaptations that induce greater neuronal activity throughout a long lifespan. High levels of neuroplasticity increase neuronal vulnerability to factors capable of triggering the lesions that are typically found in AD. Several genes related to increased neuronal activity are extremely vulnerable to factors related to old age, such as oxidative stress. Some kind of dysfunction in such genes can disrupt proper regulation of a number of pathways (neuroplasticity, axonal transport) and promote the abnormal accumulation of peptides that is characteristic of AD. Possessing certain polymorphisms of neuroprotective genes or of the electron transport chain could afford protection against AD. Increased intake of animal fats could alter the balance of polyunsaturated fatty acids in the neuronal membrane and favour a higher susceptibility to oxidative stress. CONCLUSIONS: AD could constitute an example of antagonistic pleiotropy: the increased expression of advantageous genes at an early age could turn out to be harmful at an advanced age.

Aging↗