Process Of Gene Duplication Research Articles

Genome Diversification Mechanism of Rodent and Lagomorpha Chemokine Genes

Chemokines are a large family of small cytokines that are involved in host defence and body homeostasis through recruitment of cells expressing their receptors. Their genes are known to undergo rapid evolution. Therefore, the number and content of chemokine genes can be quite diverse among the different species, making the orthologous relationships often ambiguous even between closely related species. Given that rodents and rabbit are useful experimental models in medicine and drug development, we have deduced the chemokine genes from the genome sequences of several rodent species and rabbit and compared them with those of human and mouse to determine the orthologous relationships. The interspecies differences should be taken into consideration when experimental results from animal models are extrapolated into humans. The chemokine gene lists and their orthologous relationships presented here will be useful for studies using these animal models. Our analysis also enables us to reconstruct possible gene duplication processes that generated the different sets of chemokine genes in these species.

Statistical issues associated with modeling of synonymous mutation data

The explosion of data in evolutionary bioinformatics has led to sometimes ad hoc, incomplete and even inaccurate data analyses. Taking dS data, namely, data on synonymous substitutions per synonymous sites, we go through a statistical analysis for modeling the time since duplications of genes. We explore the shortcomings of previous analyses, especially with a view towards their effect on inference for the gene duplication process. We present a statistical analysis which respects the assumptions of the models and the integrity of the data, and emphasize that exploratory data analysis, formulation of a data model, its estimation and finally, assessment of the model are important steps in a complete data analysis. Furthermore, for dS data, we develop Bayesian discrete-continuous mixture models and present analyses using two genomes.

In with the old, in with the new: the promiscuity of the duplication process engenders diverse pathways for novel gene creation.

The gene duplication process has exhibited far greater promiscuity in the creation of paralogs with novel exon-intron structures than anticipated even by Ohno. In this paper I explore the history of the field, from the neo-Darwinian synthesis through Ohno's formulation of the canonical model for the evolution of gene duplicates and culminating in the present genomic era. I delineate the major tenets of Ohno's model and discuss its failure to encapsulate the full complexity of the duplication process as revealed in the era of genomics. I discuss the diverse classes of paralogs originating from both DNA- and RNA-mediated duplication events and their evolutionary potential for assuming radically altered functions, as well as the degree to which they can function unconstrained from the pressure of gene conversion. Lastly, I explore theoretical population-genetic considerations of how the effective population size (N e) of a species may influence the probability of emergence of genes with radically altered functions.

Emergence of symmetric protein architecture from a simple peptide motif: evolutionary models.

Structural symmetry is observed in the majority of fundamental protein folds and gene duplication and fusion evolutionary processes are postulated to be responsible. However, convergent evolution leading to structural symmetry has also been proposed; additionally, there is debate regarding the extent to which exact primary structure symmetry is compatible with efficient protein folding. Issues of symmetry in protein evolution directly impact strategies for de novo protein design as symmetry can substantially simplify the design process. Additionally, when considering gene duplication and fusion in protein evolution, there are two competing models: "emergent architecture" and "conserved architecture". Recent experimental work has shed light on both the evolutionary process leading to symmetric protein folds as well as the ability of symmetric primary structure to efficiently fold. Such studies largely support a "conserved architecture" evolutionary model, suggesting that complex protein architecture was an early evolutionary achievement involving oligomerization of smaller polypeptides.

The plant genome: an evolutionary perspective on structure and function

The plant genome: an evolutionary perspective on structure and function

Genome‐wide analysis of fungal manganese transporters, with an emphasis on Phanerochaete chrysosporium

Genome-wide analysis of fungal manganese transporters was undertaken, making use of whole genome sequences available in fungal databases. A repertoire of 281 putative manganese transporters was found in total across 26 fungal species representing 20 fungal orders. The process of gene duplication was apparently accompanied by gene loss events, and this resulted in a great variety of manganese transporters that can be observed in the genome of modern fungi. Eleven transporters belonging to gene families in which manganese transporters have been found were identified in the Phanerochaete chrysosporium genome. This whole set of transporters may cover the need of P. chrysosporium cells for manganese loading in and unloading out of the cytosol, thereby insuring manganese homeostasis. The tight control of intracellular Mn(2+) ion concentration is for instance of crucial importance for the control of lignin-degradative systems by saprotrophic fungi, and thereof the carbon cycle in forest ecosystems.

Is gene duplication a viable explanation for the origination of biological information and complexity?

All life depends on the biological information encoded in DNA with which to synthesize and regulate various peptide sequences required by an organism's cells. Hence, an evolutionary model accounting for the diversity of life needs to demonstrate how novel exonic regions that code for distinctly different functions can emerge. Natural selection tends to conserve the basic functionality, sequence, and size of genes and, although beneficial and adaptive changes are possible, these serve only to improve or adjust the existing type. However, gene duplication allows for a respite in selection and so can provide a molecular substrate for the development of biochemical innovation. Reference is made here to several well-known examples of gene duplication, and the major means of resulting evolutionary divergence, to examine the plausibility of this assumption. The totality of the evidence reveals that, although duplication can and does facilitate important adaptations by tinkering with existing compounds, molecular evolution is nonetheless constrained in each and every case. Therefore, although the process of gene duplication and subsequent random mutation has certainly contributed to the size and diversity of the genome, it is alone insufficient in explaining the origination of the highly complex information pertinent to the essential functioning of living organisms. © 2011 Wiley Periodicals, Inc. Complexity, 2011 © 2011 Wiley Periodicals, Inc.

Experimental support for the evolution of symmetric protein architecture from a simple peptide motif

The majority of protein architectures exhibit elements of structural symmetry, and "gene duplication and fusion" is the evolutionary mechanism generally hypothesized to be responsible for their emergence from simple peptide motifs. Despite the central importance of the gene duplication and fusion hypothesis, experimental support for a plausible evolutionary pathway for a specific protein architecture has yet to be effectively demonstrated. To address this question, a unique "top-down symmetric deconstruction" strategy was utilized to successfully identify a simple peptide motif capable of recapitulating, via gene duplication and fusion processes, a symmetric protein architecture (the threefold symmetric β-trefoil fold). The folding properties of intermediary forms in this deconstruction agree precisely with a previously proposed "conserved architecture" model for symmetric protein evolution. Furthermore, a route through foldable sequence-space between the simple peptide motif and extant protein fold is demonstrated. These results provide compelling experimental support for a plausible evolutionary pathway of symmetric protein architecture via gene duplication and fusion processes.

Extending the family table: Insights from beyond vertebrates into the regulation of embryonic development by FGFs

Since the discovery of fibroblast growth factors (FGFs) much focus has been placed on elucidating the roles for each vertebrate FGF ligand, receptor, and regulating molecules in the context of vertebrate development, human disorders and cancer. Studies in human, mouse, frog, chick, and zebrafish have made great contributions to our understanding of the role of FGFs in specific processes. However, in recent years, as more genomes are sequenced, information is becoming available from many non-vertebrate models and a more complete picture of the FGF superfamily as a whole is emerging. In some cases, less redundancy in these FGF signaling systems may allow for more mechanistic insights. Studies in sea anemones have highlighted how ancient FGF signaling is and helped provide insight into the evolution of the FGF gene family. Work in nematodes has shown that different splice forms can be used for functional specificity in invertebrate FGF signaling. Comparing FGFs between urochordates and vertebrates as well as between different insect species reveals important clues into the process of gene loss, duplication and subfunctionalization of FGFs throughout evolution. Finally, comparing all members of the FGF ligand superfamily reveals variability in many properties, which may point to a feature of FGFs as being highly adaptable with regards to protein structure and signaling mechanism. Further studies on FGF signaling outside of vertebrates is likely to continue to complement work in vertebrates by contributing additional insights to the FGF field and providing unexpected information that could be used for medical applications.

Genomic organization of plant aminopropyl transferases

Aminopropyl transferases like spermidine synthase (SPDS; EC 2.5.1.16), spermine synthase and thermospermine synthase (SPMS, tSPMS; EC 2.5.1.22) belong to a class of widely distributed enzymes that use decarboxylated S-adenosylmethionine as an aminopropyl donor and putrescine or spermidine as an amino acceptor to form in that order spermidine, spermine or thermospermine. We describe the analysis of plant genomic sequences encoding SPDS, SPMS, tSPMS and PMT (putrescine N-methyltransferase; EC 2.1.1.53). Genome organization (including exon size, gain and loss, as well as intron number, size, loss, retention, placement and phase, and the presence of transposons) of plant aminopropyl transferase genes were compared between the genomic sequences of SPDS, SPMS and tSPMS from Zea mays, Oryza sativa, Malus x domestica, Populus trichocarpa, Arabidopsis thaliana and Physcomitrella patens. In addition, the genomic organization of plant PMT genes, proposed to be derived from SPDS during the evolution of alkaloid metabolism, is illustrated. Herein, a particular conservation and arrangement of exon and intron sequences between plant SPDS, SPMS and PMT genes that clearly differs with that of ACL5 genes, is shown. The possible acquisition of the plant SPMS exon II and, in particular exon XI in the monocot SPMS genes, is a remarkable feature that allows their differentiation from SPDS genes. In accordance with our in silico analysis, functional complementation experiments of the maize ZmSPMS1 enzyme (previously considered to be SPDS) in yeast demonstrated its spermine synthase activity. Another significant aspect is the conservation of intron sequences among SPDS and PMT paralogs. In addition the existence of microsynteny among some SPDS paralogs, especially in P. trichocarpa and A. thaliana, supports duplication events of plant SPDS genes. Based in our analysis, we hypothesize that SPMS genes appeared with the divergence of vascular plants by a processes of gene duplication and the acquisition of unique exons of as-yet unknown origin.

Gene duplications and the time thereafter - examples from plant secondary metabolism

Gene duplications are regarded as one of the central mechanisms for the origin of new genes. Recent studies in plant secondary metabolism have provided several examples of genes that originated by duplication with successive diversification. In this review, the mechanisms of gene duplication are explained and several models discussed that suggest the way that gene duplicates develop into genes with new functions. Signatures of gene duplication and diversification processes are discussed using the biosynthesis of benzoxazinones and of pyrrolizidine alkaloids as examples.

Cloning and analysis of the HMG domains of ten Sox genes from Bombina maxima (Amphibia: Anura)

Sox is a large gene family which encodes Sry-related transcription factors and contains a HMG box that is responsible for the sequence-specific DNA binding. In this paper, we obtained ten clones representing HMG box-containing Sox genes (BmSox1a, BmSox1b, BmSox3a, BmSox3b, BmSox3c, BmSox11a, BmSox11b, BmSox11c, BmSox14, BmSox33) from male and female Bombina maxima respectively and no sexual differences were observed, using highly degenerate primers designed from the conservative motif (HMG-box) of the human SRY gene. We want to reveal the gene duplication process and gene trees for the Sox genes in this toad. The sequences analysis indicated that Sox1, Sox3 and Sox11 gene may be duplicated. The cloned Sox genes shared high sequence identity to the homologous human SOX genes. Based on the amino acid sequence similarities, the phylogenetic analysis was carried out and the results suggested that nine of ten HMG domain-encoding sequences are members of the SoxB and SoxC groups. BmSox33 and its homologous gene xSox33(Xenopus laevis) were found only in Discoglossidae and Xenopodidae in amphibian, but Sox33 has not been found in other vertebrates up to now, and the origin of Sox33 gene is an interesting target in phylogenesis.

Simultaneous Bayesian gene tree reconstruction and reconciliation analysis

We present GSR, a probabilistic model integrating gene duplication, sequence evolution, and a relaxed molecular clock for substitution rates, that enables genomewide analysis of gene families. The gene duplication and loss process is a major cause for incongruence between gene and species tree, and deterministic methods have been developed to explain such differences through tree reconciliations. Although probabilistic methods for phylogenetic inference have been around for decades, probabilistic reconciliation methods are far less established. Based on our model, we have implemented a Bayesian analysis tool, PrIME-GSR, for gene tree inference that takes a known species tree into account. Our implementation is sound and we demonstrate its utility for genomewide gene-family analysis by applying it to recently presented yeast data. We validate PrIME-GSR by comparing with previous analyses of these data that take advantage of gene order information. In a case study we apply our method to the ADH gene family and are able to draw biologically relevant conclusions concerning gene duplications creating key yeast phenotypes. On a higher level this shows the biological relevance of our method. The obtained results demonstrate the value of a relaxed molecular clock. Our good performance will extend to species where gene order conservation is insufficient.

The evolution of animal chemosensory receptor gene repertoires: roles of chance and necessity

Chemosensory receptors are essential for the survival of organisms that range from bacteria to mammals. Recent studies have shown that the numbers of functional chemosensory receptor genes and pseudogenes vary enormously among the genomes of different animal species. Although much of the variation can be explained by the adaptation of organisms to different environments, it has become clear that a substantial portion is generated by genomic drift, a random process of gene duplication and deletion. Genomic drift also generates a substantial amount of copy-number variation in chemosensory receptor genes within species. It seems that mutation by gene duplication and inactivation has important roles in both the adaptive and non-adaptive evolution of chemosensation.

Genetic diversity of the Leptospiral immunoglobulin-like (Lig) genes in pathogenic Leptospira spp.

Recent serologic, immunoprotection, and pathogenesis studies identified the Lig proteins as key virulence determinants in interactions of leptospiral pathogens with the mammalian host. We examined the sequence variation and recombination patterns of ligA, ligB, and ligC among 10 pathogenic strains from five Leptospira species. All strains were found to have intact ligB genes and genetic drift accounting for most of the ligB genetic diversity observed. The ligA gene was found exclusively in L. interrogans and L. kirschneri strains, and was created from ligB by a two-step partial gene duplication process. The aminoterminal domain of LigB and the LigA paralog were essentially identical (98.5±0.8% mean identity) in strains with both genes. Like ligB, ligC gene variation also followed phylogenetic patterns, suggesting an early gene duplication event. However, ligC is a pseudogene in several strains, suggesting that LigC is not essential for virulence. Two ligB genes and one ligC gene had mosaic compositions and evidence for recombination events between related Leptospira species was also found for some ligA genes. In conclusion, the results presented here indicate that Lig diversity has important ramifications for the selection of Lig polypeptides for use in diagnosis and as vaccine candidates. This sequence information will aid the identification of highly conserved regions within the Lig proteins and improve upon the performance characteristics of the Lig proteins in diagnostic assays and in subunit vaccine formulations with the potential to confer heterologous protection.

Accelerated exchange of exon segments in Viperid three-finger toxin genes (Sistrurus catenatus edwardsii; Desert Massasauga)

BackgroundSnake venoms consist primarily of proteins and peptides showing a myriad of potent biological activities which have been shaped by both adaptive and neutral selective forces. Venom proteins are encoded by multigene families that have evolved through a process of gene duplication followed by accelerated evolution in the protein coding region.ResultsHere we report five gene structures of three-finger toxins from a viperid snake, Sistrurus catenatus edwardsii. These toxin genes are structured similarly to elapid and hydrophiid three-finger toxin genes, with two introns and three exons. Both introns and exons show distinct patterns of segmentation, and the insertion/deletion of segments may define their evolutionary history. The segments in introns, when present, are highly similar to their corresponding segments in other members of the gene family. In contrast, some segments in the exons show high similarity, while others are often distinctly different among corresponding regions of the isoforms.ConclusionOrdered, conserved exon structure strongly suggests that segments in corresponding regions in exons have been exchanged with distinctly different ones during the evolution of these genes. Such a "switching" of segments in exons may result in drastically altering the molecular surface topology and charge, and hence the molecular targets of these three-finger toxins. Thus the phenomenon of accelerated segment switch in exons to alter targeting (ASSET) may play an important role in the evolution of three-finger toxins, resulting in a family of toxins with a highly conserved structural fold but widely varying biological activities.

A protein functional leap: how a single mutation reverses the function of the transcription regulator TetR

Today's proteome is the result of innumerous gene duplication, mutagenesis, drift and selection processes. Whereas random mutagenesis introduces predominantly only gradual changes in protein function, a case can be made that an abrupt switch in function caused by single amino acid substitutions will not only considerably further evolution but might constitute a prerequisite for the appearance of novel functionalities for which no promiscuous protein intermediates can be envisaged. Recently, tetracycline repressor (TetR) variants were identified in which binding of tetracycline triggers the repressor to associate with and not to dissociate from the operator DNA as in wild-type TetR. We investigated the origin of this activity reversal by limited proteolysis, CD spectroscopy and X-ray crystallography. We show that the TetR mutant Leu17Gly switches its function via a disorder–order mechanism that differs completely from the allosteric mechanism of wild-type TetR. Our study emphasizes how single point mutations can engender unexpected leaps in protein function thus enabling the appearance of new functionalities in proteins without the need for promiscuous intermediates.

The evolution of developmental patterning under genetic duplication constraints.

Of considerable interest are the evolutionary and developmental origins of complex, adaptive structures and the mechanisms that stabilize these structures. We consider the relationship between the evolutionary process of gene duplication and deletion and the stability of morphogenetic patterns produced by interacting activators and inhibitors. We compare the relative stability of patterns with a single activator and inhibitor (two-dimensional system) against a 'redundant' system with two activators or two inhibitors (three-dimensional system). We find that duplication events can both expand and contract the space of patterns. We study developmental robustness in terms of stochastic escape times from this space, also known as a 'canalization potential'. We embed the output of pattern formation into an explicit evolutionary model of gene duplication, gene loss and variation in the steepness of the canalization potential. We find that under all constant conditions, the system evolves towards a preference for steep potentials associated with low phenotypic variability and longer lifespans. This preference leads to an overall decrease in the density of redundant genotypes as developmental robustness neutralizes the advantages of genetic robustness.

The chemokine network. I. How the genomic organization of chemokines contains clues for deciphering their functional complexity

Chemokines are a superfamily of small structurally related cytokines that have evolved to form a complex network of proteins that typically regulate leucocyte traffic but also carry very diverse sets of immune and non-immune functions. Two general features of cytokines, redundancy and promiscuity, are particularly prominent in chemokines. In part, these properties result from repeated processes of gene duplication and diversification, which has led to the present complex genomic map of chemokines, which contains cases of non-allelic isoforms, copy number polymorphisms and classical allelic variation. This genomic complexity is compounded with pre-translational and post-translational mechanisms resulting in a complex network of proteins whose essential functions are maintained, constituting a remarkable case of robustness reminiscent of crucial metabolic pathways. This reflects the adaptation of a system under strong evolutive pressure, supporting the concept that the chemokine system is essential for the coordination, regulation and fine-tuning of the type of immune response. In this first review, we analyse currently available data on the chemokine superfamily, focusing on its complex genomic organization. Genes encoding essential inflammatory chemokines are grouped into defined chromosomal locations as clusters and miniclusters that, from the genetic point of view, can be considered single entities given their overall functions (many ligands of a cluster bind to a few shared receptors). We will try to interpret this genomic organization of chemokines in relation to the main functions acquired by each individual member or by each cluster. In a second review, we shall focus on the relationship of chemokine variability and disease susceptibility.

The Generation of New Protein Functions by the Combination of Domains

During evolution, many new proteins have been formed by the process of gene duplication and combination. The genes involved in this process usually code for whole domains. Small proteins contain one domain; medium and large proteins contain two or more domains. We have compared homologous domains that occur in both one-domain proteins and multidomain proteins. We have determined (1) how the functions of the individual domains in the multidomain proteins combine to produce their overall functions and (2) the extent to which these functions are similar to those in the one-domain homologs. We describe how domain combinations increase the specificity of enzymes; act as links between domains that have functional roles; regulate activity; combine within one chain functions that can act either independently, in concert or in new contexts; and provide the structural framework for the evolution of entirely new functions.