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[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↗
PubMed1994

Genomic structure, expression and evolution of the alfalfa aspartate aminotransferase genes.

Genomic clones encoding two isozymes of aspartate aminotransferase (AAT) were isolated from an alfalfa genomic library and their DNA sequences were determined. The AAT1 gene contains 12 exons that encode a cytosolic protein expressed at similar levels in roots, stems and nodules. In nodules, the amount of AAT1 mRNA was similar at all stages of development, and was slightly reduced in nodules incapable of fixing nitrogen. The AAT1 mRNA is polyadenylated at multiple sites differing by more than 250 bp. The AAT2 gene contains 11 exons, with 5 introns located in positions identical to those found in animal AAT genes, and encodes a plastid-localized isozyme. The AAT2 mRNA is polyadenylated at a very limited range of sites. The transit peptide of AAT2 is encoded by the first two and part of the third exon. AAT2 mRNA is much more abundant in nodules than in other organs, and increases dramatically during the course of nodule development. Unlike AAT1, expression of AAT2 is significantly reduced in nodules incapable of fixing nitrogen. Phylogenetic analysis of deduced AAT proteins revealed 4 separate but related groups of AAT proteins; the animal cytosolic AATs, the plant cytosolic AATs, the plant plastid AATs, and the mitochondrial AATs.

Amino Acid Sequence↗
PubMed1998

An amphioxus snail gene: expression in paraxial mesoderm and neural plate suggests a conserved role in patterning the chordate embryo.

Homologs of the Drosophila snail gene have been characterized in several vertebrates. In addition to being expressed in mesoderm during gastrulation, vertebrate snail genes are also expressed in presumptive neural crest and/or its derivatives. Given that neural crest is unique to vertebrates and is considered to be of fundamental importance in their evolution, we have cloned and characterized the expression of a snail gene from amphioxus, a cephalochordate widely accepted as the sister group of the vertebrates. We show that, at the amino acid sequence level, the amphioxus snail gene is a clear phylogenetic outgroup to all the characterized vertebrate snail genes. During embryogenesis snail expression initially becomes restricted to the paraxial or presomitic mesoderm of amphioxus. Later, snail is expressed at high levels in the lateral neural plate, where it persists during neurulation. Our results indicate that an ancestral function of snail genes in the lineage leading to vertebrates is to define the paraxial mesoderm. Furthermore, our results indicate that a cell population homologous to the vertebrate neural crest may be present in amphioxus, thus providing an important link in the evolution of this key vertebrate tissue.

Amino Acid Sequence↗
PubMed2000

Do the constraints of human speciation cause expression of the same set of genes in brain, testis, and placenta?

Evolution appears to be especially rapid during speciation, and the genes involved in speciation should be evident in species such as humans that have recently speciated or are presently in the process of speciation. Haldane's rule is that when one sex is sterile or inviable in interspecific F(1) hybrids, it is usually the heterogametic sex. For mammals, this implicates genes on the X chromosome as those particularly responsible for speciation. A preponderance of sex- and reproduction-related genes on the X chromosome has been shown repeatedly, but also mental retardation genes are more frequent on the X chromosome. We argue that brain, testis, and placenta are those organs most responsible for human speciation. Furthermore, the high degree of complexity of the vertebrate genome demands coordinate evolution of new characters. This coordination is best attained when the same set of genes is redeployed for these new characters in the brain, testis, and placenta.

Biological Evolution↗
PubMed1997

Evolution of the insect body plan as revealed by the Sex combs reduced expression pattern.

The products of the HOM/Hox homeotic genes form a set of evolutionarily conserved transcription factors that control elaborate developmental processes and specify cell fates in many metazoans. We examined the expression of the ortholog of the homeotic gene Sex combs reduced (Scr) of Drosophila melanogaster in insects of three divergent orders: Hemiptera, Orthoptera and Thysanura. Our data reflect how the conservation and variation of Scr expression has affected the morphological evolution of insects. Whereas the anterior epidermal expression of Scr, in a small part of the posterior maxillary and all of the labial segment, is found to be in common among all four insect orders, the posterior (thoracic) expression domains vary. Unlike what is observed in flies, the Scr orthologs of other insects are not expressed broadly over the first thoracic segment, but are restricted to small patches. We show here that Scr is required for suppression of wings on the prothorax of Drosophila. Moreover, Scr expression at the dorsal base of the prothoracic limb in two other winged insects, crickets (Orthoptera) and milkweed bugs (Hemiptera), is consistent with Scr acting as a suppressor of prothoracic wings in these insects. Scr is also expressed in a small patch of cells near the basitarsal-tibial junction of milkweed bugs, precisely where a leg comb develops, suggesting that Scr promotes comb formation, as it does in Drosophila. Surprisingly, the dorsal prothoracic expression of Scr is also present in the primitively wingless firebrat (Thysanura) and the leg patch is seen in crickets, which have no comb. Mapping both gene expression patterns and morphological characters onto the insect phylogenetic tree demonstrates that in the cases of wing suppression and comb formation the appearance of expression of Scr in the prothorax apparently precedes these specific functions.

Amino Acid Sequence↗
PubMed2003

Expression of foreign genes in lamprey embryos: an approach to study evolutionary changes in gene regulation.

Evolution in development can be viewed as a sequence of changes in gene regulation. To investigate the cross-species compatibility of 5' upstream regulatory regions, we introduced exogenous gene constructs derived from a gnathostome genome into fertilized eggs of the Japanese lamprey, Lampetra japonica, a sister group of the gnathostomes. Eggs were injected with gene constructs in which a sequence encoding the green fluorescent protein (GFP) had been located downstream of either a virus promoter or 5' regulatory regions of medaka actin genes. Reporter gene expression was recorded for more than a month starting two days after injection. Although the expression patterns were highly mosaic and differed among individuals, GFP was expressed predominantly in the striated muscles of lamprey embryos when driven by the 5' upstream regions of the medaka muscle actin genes. This implies that a pan-vertebrate muscle-specific gene regulatory mechanism may have evolved before the agnathan/gnathostome divergence. This gene-transfer technique potentially facilitates the visualization of cells in various differentiating tissues throughout development. The introduction of developmental genes of the lamprey or other animals into lamprey embryos is another potentially important application, one that could provide us with information on the evolutionary changes in functions of genes or gene cascades.

Actins↗
PubMed1994

Developmental expression of the mouse Evx-2 gene: relationship with the evolution of the HOM/Hox complex.

The mouse Evx-2 gene is located in the immediate vicinity of the Hoxd-13 gene, the most posteriorly expressed gene of the HOXD complex. While the Evx-1 gene is also physically linked to the HOXA complex, it is more distantly located from the corresponding Hoxa-13 gene. We have analysed the expression of Evx-2 during development and compared it to that of Evx-1 and Hoxd-13. We show that, even though Evx-2 is expressed in the developing CNS in a pattern resembling that of other Evx-related genes, the overall expression profile is similar to that of the neighbouring limbs and genitalia. We propose that the acquisition of expression features typical of Hox genes, together with the disappearance of some expression traits common to Evx genes, is due to the close physical linkage of Evx-2 to the HOXD complex, which results in Evx-2 expression being partly controlled by mechanisms acting in the HOX complex. This transposition of the Evx-2 gene next to the Hoxd-13 gene may have occurred soon after the large scale duplications of the HOX complexes. A scheme is proposed to account for the functional evolution of eve-related genes in the context of their linkage to the HOM/Hox complexes.

Animals↗
PubMed2004

Elevated rates of protein secretion, evolution, and disease among tissue-specific genes.

Variation in gene expression has been held responsible for the functional and morphological specialization of tissues. The tissue specificity of genes is known to correlate positively with gene evolution rates. We show here, using large data sets, that when a gene is expressed highly in a small number of tissues, its protein is more likely to be secreted and more likely to be mutated in genetic diseases with Mendelian inheritance. We find that secreted proteins are evolving at faster rates than nonsecreted proteins, and that their evolutionary rates are highly correlated with tissue specificity. However, the impact of secretion on evolutionary rates is countered by tissue-specific constraints that have been held constant over the past 75 million years. We find that disease genes are underrepresented among intracellular and slowly evolving housekeeping genes. These findings illuminate major selective pressures that have shaped the gene repertoires expressed in different mammalian tissues.

Animals↗
PubMed1993

Structure, evolution and expression of the mitochondrial ADP/ATP translocator gene from Chlamydomonas reinhardtii.

The first AUG in the Chlamydomonas reinhardtii ADP/ATP translocator (CRANT) mRNA initiates an open reading frame (ORF) which is very similar (51-79% amino acid identity) to other ANT proteins. In contrast to higher plants, no evidence for a long amino-terminal extension was obtained. The 5' non-transcribed region of the single-copy CRANT gene contains sequence motifs present in other C. reinhardtii nuclear genes. Four introns, whose positions are not conserved in other ANT genes, interrupt the protein coding region. A short heat shock specifically reduces CRANT mRNA levels. CRANT mRNA levels were unaffected by a mutation in photosynthesis. In a dark/light regime CRANT mRNA levels are high in the dark phase and low in the early light phase. Data on translation initiation sites, splice junctions and the codon preferences of C. reinhardtii nuclear genes were compiled. With the exception of two rare codons, ACA and GGA, the CRANT gene exhibits the biased codon usage of C. reinhardtii nuclear genes that are highly expressed during normal vegetative growth.

Amino Acid Sequence↗
PubMed2000

Bacterial virulence gene regulation: an evolutionary perspective.

Coevolution between bacteria and their plant or animal hosts determines characteristics of the interaction, the bacterial virulence genes involved, and the regulatory systems controlling expression of virulence genes. The long-standing association between Salmonellae and their animal hosts has resulted in the acquisition by Salmonella subspecies of a variety of virulence genes and the evolution of complex regulatory networks. The particular repertoire of virulence genes acquired by different Salmonella enterica subspecies and the regulatory systems that control them dictate subspecies-specific infection characteristics. Although the association between Vibrio cholerae and humans appears to be more recent, to reflect a simpler pathogenic strategy, and to involve fewer virulence genes than that of Salmonellae, complex virulence-regulatory networks have nonetheless evolved. In contrast, there is no evidence for acquisition of virulence genes by horizontal gene transfer in bordetellae, and their virulence regulon is less complex in overall structure than those of salmonellae and Vibrio cholerae. In Bordetellae, subspecies-specific differences in pathogenic strategy appear to result from differential gene expression within and across Bordetella subspecies.

Biological Evolution↗
PubMed2002

Cytochrome P450 and actin genes expressed in Helicoverpa zea and Helicoverpa armigera: paralogy/orthology identification, gene conversion and evolution.

Molecular phylogenetic analysis was conducted using conserved cytoplasmic actin and diversified cytochrome P450 (P450) sequences isolated from Helicoverpa zea and Helicoverpa armigera, two species thought to be closely related based on allozyme analyses. These sequences were compared in turn with published sequences from other insects to gain insight into how different gene families evolve. In Bombyx mori and these Helicoverpa species, cytoplasmic actin genes are present as a pair of tandemly duplicated paralogs with coding sequence identities as high as 95.5% (B. mori), 98.9% (H. zea) and 98.5% (H. armigera) due to recent 5'-polar gene conversions. Phylogeny and interspecies comparisons assign the six actin genes into two orthologous groups: HaA3a/HzA3a/BmA3 and HaA3b/HzA3b/BmA4, which exhibit more similarities between H. zea and H. armigera than between Helicoverpa species and B. mori. Like the actin genes in H. zea, four CYP6B genes exist as two pairs of duplicated paralogs with recent 5'-polar gene conversions. Interspecific comparisons and phylogeny analysis identified three groups of orthologous CYP6B genes: H. zea CYP6B8 or CYP6B28/H. armigera CYP6B7, H. zea CYP6B27/H. armigera CYP6B6, and H. zea CYP6B9/H. armigera CYP6B2/Heliothis virescens CYP6B10. The low degree of divergence in the first two of these groups is comparable to allelic variation within a single species. These orthologous relationships and the high degrees of similarity in both actin and P450 genes strongly indicate that these Helicoverpa species are extremely closely related.

Actins↗
PubMed2005

Chaperones and longevity.

That evolution of longevity may depend on alterations in the expression of relatively few regulatory genes has been inferred from the rapid increase in lifespan during evolution of the hominid species (Cutler RG (1979) Mech Ageing Dev 9: 337-354). Also the inherent immortality of the embryonic stem cells implies that replicative senescence (Hayflick L (1997) Biochem Mosc 62: 1180-1190) as possibly aging of species are epigenetic phenomena. Evidence is presented to suggest that the epigenetic changes of the longevity determinants to a significant extend concerns the molecular chaperones. Specific involvement of RNA chaperones in cell immortalization and defective RecQ-DNA chaperones in syndromes of premature aging suggest that DNA/RNA - chaperones probably rank high among the determinants of cellular and species longevity.

Animals↗
PubMed2000

Differential expression of orthologous Dlx genes in zebrafish and mice: implications for the evolution of the Dlx homeobox gene family.

Dlx homeobox genes of vertebrates are often organised as physically linked pairs in which the two genes are transcribed convergently (tail-to-tail arrangement). Three such Dlx pairs have been found in mouse, human, and zebrafish and are thought to have originated from the duplication of an ancestral gene pair. These pairs include Dlx1/Dlx2, Dlx7/Dlx3, and Dlx6/Dlx5 (the zebrafish orthologue of Dlx5 is named dlx4). Expression patterns of physically linked Dlx genes overlap extensively. Furthermore, orthologous Dlx genes often show highly similar expression patterns. We analysed Dlx expression during the gastrula and early somitogenesis of the mouse and zebrafish. It was found that expression of the mouse Dlx6 gene takes place in the rostral ectoderm and presumptive olfactory and otic placodes with patterns similar to the previously reported expression of the physically linked Dlx5 gene. However, we observed only very weak expression of the mouse Dlx3 gene at the same stage. This contrasts with the expression of dlx genes in zebrafish where dlx3 and dlx7, but not dlx4 and dlx6 are expressed during gastrulation in the rostral ectoderm and presumptive placodes. Thus, Dlx expression patterns at early stages are better conserved between paralogous pairs of physically linked genes than between orthologous pairs. This suggests that early expression of Dlx genes existed prior to the duplications that led to the multiple pairs of physically linked genes but was differentially conserved in different paralogs in zebrafish and mice.

Animals↗
PubMed1997

Radical alterations in the roles of homeobox genes during echinoderm evolution.

Echinoderms possess one of the most highly derived body architectures of all metazoan phyla, with radial symmetry, a calcitic endoskeleton, and a water vascular system. How these dramatic morphological changes evolved has been the subject of extensive speculation and debate, but remains unresolved. Because echinoderms are closely related to chordates and postdate the protostome/deuterostome divergence, they must have evolved from bilaterally symmetrical ancestors. Here we report the expression domains in echinoderms of three important developmental regulatory genes (distal-less, engrailed and orthodenticle), all of which encode transcription factors that contain a homeodomain. Our findings show that the reorganization of body architecture involved extensive changes in the deployment and roles of homeobox genes. These changes include modifications in the symmetry of expression domains and the evolution of several new developmental roles, as well as the loss of roles conserved between arthropods and chordates. Some of these modifications seem to have evolved very early in the history of echinoderms, whereas others probably evolved during the subsequent diversification of adult and larval morphology. These results demonstrate the evolutionary lability of regulatory genes that are widely viewed as conservative.

Animals↗
PubMed2003

Genes duplicated by polyploidy show unequal contributions to the transcriptome and organ-specific reciprocal silencing.

Most eukaryotes have genomes that exhibit high levels of gene redundancy, much of which seems to have arisen from one or more cycles of genome doubling. Polyploidy has been particularly prominent during flowering plant evolution, yielding duplicated genes (homoeologs) whose expression may be retained or lost either as an immediate consequence of polyploidization or on an evolutionary timescale. Expression of 40 homoeologous gene pairs was assayed by cDNA-single-stranded conformation polymorphism in natural (1- to 2-million-yr-old) and synthetic tetraploid cotton (Gossypium) to determine whether homoeologous gene pairs are expressed at equal levels after polyploid formation. Silencing or unequal expression of one homoeolog was documented for 10 of 40 genes examined in ovules of Gossypium hirsutum. Assays of homoeolog expression in 10 organs revealed variable expression levels and silencing, depending on the gene and organ examined. Remarkably, silencing and biased expression of some gene pairs are reciprocal and developmentally regulated, with one homoeolog showing silencing in some organs and the other being silenced in other organs, suggesting rapid subfunctionalization. Duplicate gene expression was examined in additional natural polyploids to characterize the pace at which expression alteration evolves. Analysis of a synthetic tetraploid revealed homoeolog expression and silencing patterns that sometimes mirrored those of the natural tetraploid. Both long-term and immediate responses to polyploidization were implicated. Data suggest that some silencing events are epigenetically induced during the allopolyploidization process.

DNA, Plant↗
PubMed1993

Evolution and expression of a beta-like globin gene of the Australian marsupial Sminthopsis crassicaudata.

A beta-like globin gene was isolated from the Australian dasyurid marsupial Sminthopsis crassicaudata. Nucleotide-sequence analysis of promoter and coding regions of the gene revealed that it was orthologous to eutherian early-expressed (epsilon, gamma, eta) beta-like globin genes. Comparison of the conceptually translated sequence of the gene with a partial amino acid sequence of the adult beta-globin chain from S. crassicaudata provided evidence that the gene was not expressed in adult tissues. In addition, Northern analysis of RNA isolated from an embryo, pouch young, and adult bone marrow indicated that the gene was expressed predominantly in embryonic tissues and that there was a significant reduction in the expression of the gene within a day of birth. These results provide strong support for the hypothesis of Koop and Goodman [Koop, B. F. & Goodman, M. (1988) Proc. Natl. Acad. Sci. USA 85, 3893-3897] that an embryonic beta-like globin gene existed prior to the divergence of the eutherian and marsupial lineages and that this gene was already differentiated with respect to its promoter regions and developmental expression. The observation that epsilon-globin mRNA was present at least until day 4 postpartum suggests that the epsilon-globin chain may play some role in influencing the physiological properties of hemoglobin in S. crassicaudata neonates.

Aging↗