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PubMed2003

Gene duplication, the evolution of novel gene functions, and detecting functional divergence of duplicates in silico.

Duplication of genes increases the amount of genetic material on which evolution can work and has been considered of major importance for the development of biological novelties or to explain important transitions that have occurred during biological evolution. Recently, much research has been devoted to the study of the evolutionary and functional divergence of duplicated genes. Since the majority of genes are part of gene families, there is considerable interest in predicting differences in function between duplicates and assessing the functional redundancy of genes within gene families. In this review, we discuss the strengths and limitations of both older and novel approaches to investigate the evolution of duplicated genes in silico.

Algorithms↗
PubMed2003

Convergent evolution of gene circuits.

Convergent evolution is a potent indicator of optimal design. We show here that convergent evolution occurs in genetic networks. Specifically, we show that multiple types of transcriptional regulation circuitry in Escherichia coli and the yeast Saccharomyces cerevisiae have evolved independently and not by duplication of one or a few ancestral circuits.

Escherichia coli↗
PubMed2003

Cardiac chamber formation: development, genes, and evolution.

Concepts of cardiac development have greatly influenced the description of the formation of the four-chambered vertebrate heart. Traditionally, the embryonic tubular heart is considered to be a composite of serially arranged segments representing adult cardiac compartments. Conversion of such a serial arrangement into the parallel arrangement of the mammalian heart is difficult to understand. Logical integration of the development of the cardiac conduction system into the serial concept has remained puzzling as well. Therefore, the current description needed reconsideration, and we decided to evaluate the essentialities of cardiac design, its evolutionary and embryonic development, and the molecular pathways recruited to make the four-chambered mammalian heart. The three principal notions taken into consideration are as follows. 1) Both the ancestor chordate heart and the embryonic tubular heart of higher vertebrates consist of poorly developed and poorly coupled "pacemaker-like" cardiac muscle cells with the highest pacemaker activity at the venous pole, causing unidirectional peristaltic contraction waves. 2) From this heart tube, ventricular chambers differentiate ventrally and atrial chambers dorsally. The developing chambers display high proliferative activity and consist of structurally well-developed and well-coupled muscle cells with low pacemaker activity, which permits fast conduction of the impulse and efficacious contraction. The forming chambers remain flanked by slowly proliferating pacemaker-like myocardium that is temporally prevented from differentiating into chamber myocardium. 3) The trabecular myocardium proliferates slowly, consists of structurally poorly developed, but well-coupled, cells and contributes to the ventricular conduction system. The atrial and ventricular chambers of the formed heart are activated and interconnected by derivatives of embryonic myocardium. The topographical arrangement of the distinct cardiac muscle cells in the forming heart explains the embryonic electrocardiogram (ECG), does not require the invention of nodes, and allows a logical transition from a peristaltic tubular heart to a synchronously contracting four-chambered heart. This view on the development of cardiac design unfolds fascinating possibilities for future research.

Animals↗
PubMed1986

[Evolution of the hemagglutinin gene of influenza A virus H1N1-subtype (1977-1983].

A scheme for evolutionary interrelations of the H1-subunits of influenza hemagglutinin genes is proposed for the natural variants of influenza A virus of the H1N1-subtype. It is based on experimental data obtained by the authors and those reported in the literature. Differences among these viral isolates in their amino acid sequences and in the reaction of hemagglutinin inhibition obtained with a set of monoclonal antibodies are compared. The distinctions in the ability of the viruses to react with several monoclonal antibodies are attributed to differences in the primary structures of their hemagglutinins. Some aspects of hemagglutinin gene evolution are discussed in relation to vaccination.

Amino Acid Sequence↗
PubMed1997

[Homology and evolution of gene orders: simulation and reconstruction of the evolutionary process].

A method to reconstruct the evolutionary history of observed gene orders from estimates of their similarity has been developed. It was shown that similarity measures accounting or not accounting for gene order in linkage groups of the compared genomes can be used for this purpose. A number of plausible variants of gene-order evolution from the common ancestral form in seven primate species were obtained.

Animals↗
PubMed2005

Genes and homology in nervous system evolution: comparing gene functions, expression patterns, and cell type molecular fingerprints.

The evolution of the nervous system is one of the most fascinating, but also most nebulous fields of homology research. We do not know for example whether the last common ancestors of human, squid, and fly already possessed an elaborate brain and eyes, or rather had a simple, diffuse nervous system. Nevertheless, in the past decade molecular data has greatly advanced our understanding of bilaterian nervous system evolution. In this methodological review, I explain the four levels on which molecular genetic studies advance the quest for homologies between animal nervous systems. (I) Bioinformatic homology research elucidates the evolutionary history of gene families relevant for nervous system evolution such as the opsin superfamily. It tells us when and in what order genes and their functions have emerged. Based on this, we can (II) infer the organismal complexity of some remote ancestor from the functional diversity of its reconstructed proteome. (III) Most common in molecular homology research has been the comparison of expression patterns of developmental control genes. This approach matches and aligns embryonic regions along the body axes, between remote bilaterians. It does not tell us much, however, about the complexity of structures that developed from these regions in Urbilateria. (IV) This is overcome by a novel variant of molecular homology research, the comparison of cell types. Here, a similar "molecular fingerprint" of cells is taken as indication of cross-bilaterian homology. This approach makes it possible to reconstruct the cell-type repertoire of the urbilaterian nervous system.

Animals↗
PubMed2000

Predictions of gene family distributions in microbial genomes: evolution by gene duplication and modification.

A universal property of microbial genomes is the considerable fraction of genes that are homologous to other genes within the same genome. The process by which these homologues are generated is not well understood, but sequence analysis of 20 microbial genomes unveils a recurrent distribution of gene family sizes. We show that a simple evolutionary model based on random gene duplication and point mutations fully accounts for these distributions and permits predictions for the number of gene families in genomes not yet complete. Our findings are consistent with the notion that a genome evolves from a set of precursor genes to a mature size by gene duplications and increasing modifications.

Bacillus subtilis↗
PubMed2002

The ADAMDEC1 (decysin) gene structure: evolution by duplication in a metalloprotease gene cluster on chromosome 8p12.

Members of the ADAM superfamily of metalloprotease genes are involved in a number of biological processes, including fertilization, neurogenesis, muscle development, and the immune response. These proteins have been classified into several groups. The prototypic ADAM family is comprised of a pro-domain, a metalloprotease domain, a disintegrin domain, a cysteine-rich region, a transmembrane domain, and a variable cytoplasmic tail. We recently identified a novel member of this superfamily, ADAMDEC1 (decysin). Due to the partial lack of a disintegrin domain and the total lack of a cysteine-rich domain, this protein has been placed in a novel subclass of the ADAM gene family. We have investigated the gene structure of the human and mouse ADAMDEC1 and have revealed a metalloprotease gene cluster on human Chromosome 8p12 comprising ADAMDEC1, ADAM7, and ADAM28. Our results suggest that ADAMDEC1 has arisen by partial gene duplication from an ancestral gene at this locus and has acquired a novel function. ADAMDEC1 is expressed in the immune system, by dendritic cells and macrophages. The relatedness of ADAMDEC1, ADAM7, and ADAM28 suggests that these proteases share a similar function.

ADAM Proteins↗
PubMed1995

A nuclear gene of eubacterial origin in Euglena gracilis reflects cryptic endosymbioses during protist evolution.

Genes for glycolytic and Calvin-cycle glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of higher eukaryotes derive from ancient gene duplications which occurred in eubacterial genomes; both were transferred to the nucleus during the course of endosymbiosis. We have cloned cDNAs encoding chloroplast and cytosolic GAPDH from the early-branching photosynthetic protist Euglena gracilis and have determined the structure of its nuclear gene for cytosolic GAPDH. The gene contains four introns which possess unusual secondary structures, do not obey the GT-AG rule, and are flanked by 2- to 3-bp direct repeats. A gene phylogeny for these sequences in the context of eubacterial homologues indicates that euglenozoa, like higher eukaryotes, have obtained their GAPDH genes from eubacteria via endosymbiotic (organelle-to-nucleus) gene transfer. The data further suggest that the early-branching protists Giardia lamblia and Entamoeba histolytica--which lack mitochondria--and portions of the trypanosome lineage have acquired GAPDH genes from eubacterial donors which did not ultimately give rise to contemporary membrane-bound organelles. Evidence that "cryptic" (possibly ephemeral) endosymbioses during evolution may have entailed successful gene transfer is preserved in protist nuclear gene sequences.

Amino Acid Sequence↗
PubMed2002

Evolution of nitric oxide synthase regulatory genes by DNA inversion.

DNA inversions are mutations involving major rearrangements of the genome and are often regarded as either deleterious or catastrophic to gene function and can be associated with genomic disorders, such as Hunter syndrome and some forms of hemophilia. Here, we propose that DNA inversions are also an essential and hitherto unrecognized component of gene evolution in eukaryotic cells. Specifically, we provide evidence that an ancestral neuronal nitric oxide synthase (nNOS) gene was duplicated and that one copy retained its original function, whereas an internal DNA inversion occurred in the other. Crucially, the inversion resulted in the creation of new regulatory elements required for the termination and activation of transcription. In consequence, the duplicated gene was split, and two new and independently expressed genes were created. Through its dependence on DNA inversion, this is a fundamentally new scheme for gene evolution, which we show as being of particular relevance to the generation of endogenous antisense-containing RNA molecules. Functionally, such transcripts can operate as natural negative regulators of the expression of the genes to which they are related through a common ancestor.

Animals↗
PubMed2001

Resistance gene complexes: evolution and utilization.

More than 30 genes have been characterized from different plant species that provide resistance to a variety of different pathogen and pest species. The structures of most are consistent with a role in pathogen recognition and defense response signaling. Resistance genes are very abundant in plant genomes and most belong to tightly linked gene families. Evolution of R genes is driven by selection on allelic variation created by mutation and re-assorted by recombination between alleles and sometimes between different gene family members. Selection favors genes that can recognize pathogen avr gene products that are present in pathogen populations. Selection at linked gene families favors haplotypes with useful combinations of genes but a limited physiological cost to the plant. Future utilization of R genes will include transfer between related genera and identification or construction of genes that condition durable resistance to variable pathogens. Genes with durable resistance may interact with conserved pathogen elicitors or condition resistance responses that are independent of specific Avr gene interactions.

Evolution, Molecular↗
PubMed1986

Egg-laying hormone genes of Aplysia: evolution of the ELH gene family.

Evolution of the egg-laying hormone (ELH) gene family was examined in the genus Aplysia using genomic Southern blotting, gene cloning, and immunocytochemical techniques to identify and characterize homologous sequences. Most of the species examined have fewer than the 4-5 ELH-related genes present in the A. californica genome (Mahon et al., 1985; Scheller et al., 1983). In A. parvula there are 2 ELH genes, and unlike A. californica, no sequences were found to encode the A or B peptides. The 2 A. parvula ELH genes share at least 90% DNA sequence homology, while the homology between the A. parvula and A. californica ELH genes is 71%. The structural organization of the A. parvula ELH precursor is quite similar to the ELH precursor of A. californica, with all but one of the potential proteolytic cleavage sites conserved. The overall amino acid homology between the A. parvula and A. californica ELH precursors is 66%; however, the alpha and beta bag cell peptides, as well as ELH, are more highly conserved, suggesting that these peptides have important physiological and behavioral roles within both Aplysia species. Immunocytochemical studies indicate that the A. parvula ELH genes are expressed in 2 bag-cell-like clusters of about 40 neurons each in the abdominal ganglion. There does not appear to be an atrial gland in A. parvula; however, ELH-immunoreactive peripheral neurons and their processes are observed along the perimeter of the large hermaphroditic duct.

Animals↗
PubMed1982

Structure of human immunoglobulin gamma genes: implications for evolution of a gene family.

We have cloned five human immunoglobulin gamma genes from a fetal liver gene library. Four of them encode the known human immunoglobulin gamma chains gamma 1, gamma 2, gamma 3 and gamma 4. A fifth gamma gene seems to be a pseudogene. Nucleotide sequence determination demonstrates that the gamma 3 gene contains four separate hinge exons. Comparison of these hinge exons with those of the other gamma genes indicates that the first hinge exon is homologous to that of the pseudogene, and that the other three hinge exons are homologous to that of the gamma 1 gene, suggesting that the gamma 3 gene ancestor is a hybrid gene created by unequal crossing-over between the ancestral gamma 1 and psi gamma genes. Amplification of the gamma 1-type hinge exon probably followed to complete the gamma 3 gene. This hypothesis inevitably postulates the gene order 5'-gamma 1-gamma 3-psi gamma-3'. Cloning of overlapping chromosomal segments demonstrates that the gamma 2 gene is located 19 kb 5' to the gamma 4 gene. These analyses indicate that the human gamma-gene family has evolved by several types of DNA rearrangemet, including duplication of a complete gene; duplication of a hinge exon; and reassortment of exons by unequal cross-over between two adjacent genes.

Animals↗
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↗
PubMed2024

Gene transfer agents: The ambiguous role of selfless viruses in genetic exchange and bacterial evolution.

Gene transfer agents (GTAs) are genetic elements derived from ancestral bacteriophages that have become domesticated by the host. GTAs are present in diverse prokaryotic organisms, where they can facilitate horizontal gene transfer under certain conditions. Unlike typical bacteriophages, GTAs do not exhibit any preference for the replication or transfer of the genes encoding them; instead, they exhibit a remarkable capacity to package chromosomal, and sometimes extrachromosomal, DNA into virus-like capsids and disseminate it to neighboring cells. Because GTAs resemble defective prophages, identification of novel GTAs is not trivial. The detection of candidates relies on the genetic similarity to known GTAs, which has been fruitful in α-proteobacterial lineages but challenging in more distant bacteria. Here we consider several fundamental questions: What is the true prevalence of GTAs in prokaryote genomes? Given there are high costs for GTA production, what advantage do GTAs provide to the bacterial host to justify their maintenance? How is the bacterial chromosome recognized and processed for inclusion in GTA particles? This article highlights the challenges in comprehensively understanding GTAs' prevalence, function and DNA packaging method. Going forward, broad study of atypical GTAs and use of ecologically relevant conditions are required to uncover their true impact on bacterial chromosome evolution.

Gene Transfer, Horizontal↗
PubMed2002

Multispecies comparison of the casein gene loci and evolution of casein gene family.

Caseins, the major milk proteins, are present in a genomic cluster spanning 250-350 kb. The divergence at the coding level between human, rodent, and cattle sequences is rather extensive for most of the genes in this region. Nevertheless, comparative analysis of genomic sequences harboring the casein gene cluster region of these species (with equal evolutionary distances 79-88 Myr) shows that the organization and orientation of the genes is highly conserved. The conserved gene structure indicates that the molecular diversity of the casein genes is achieved through variable use of exons in different species and high evolutionary divergence. Comparative analysis also revealed the presence within two species of uncharacterized casein family members and ruled out the previously held notion that another gene family, located in this region, is primate-specific. Several other new genes as well as conserved noncoding sequences with potential regulatory functions were identified. All genes identified in this region are, or are predicted to be, secreted proteins involved in mineral homeostasis, nutrition, and/or host defense, and are mostly expressed in the mammary and/or salivary glands. These observations suggest a possible common ancestry for the genes in this region.

Amino Acid Sequence↗
PubMed2005

PAP IB, a new member of the Reg gene family: cloning, expression, structural properties, and evolution by gene duplication.

Reg proteins are expressed in various organs and are involved in cancers and neurodegenerative diseases. They display a typical C-type lectin-like domain but possess additional highly conserved amino acids. By studying human databases and Expressed Sequence Tags library, we identified a new member called PAP IB. Using probabilistic approaches, we established a phylogenetic tree of eighteen Reg proteins. The dendogram showed that they constitute a superfamily composed of three distinct families (FI to FIII) of paralogues that resulted from duplication. We therefore focused on two proteins, REG Ialpha and PAP IB, belonging to the more closely related FI and FII families, respectively. REG Ialpha and PAP IB share 50% sequence identity. After cloning PAP IB, however, we found that it was expressed almost only in pancreas, unlike REG Ialpha, whose expression is ubiquitous. In addition, by building a model of the structure of PAP IB based on the X-ray structure of REG Ialpha, we observed that the two proteins displayed distinctive surface charge distribution, which may lead to different ligands binding. In spite of their common fold that should result in closely related functions, REG Ialpha and PAP IB are a good example of duplication and divergence, probably with the acquisition of new functions, thus participating in the evolution of the protein repertoire.

Amino Acid Sequence↗