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Comparative genomics and evolution of the alpha-defensin multigene family in primates.

ABSTRACT: Defensin genes encode small cationic antimicrobial peptides that form an important part of the innate immune system. They are divided into three families, alpha (?), beta (?), and theta (), according to arrangement of the disulfide bonding pattern between cysteine residues. Considering the functional importance of defensins, investigators have studied the evolution and the genomic organization of defensin genes. However, these studies have been restricted mainly to ?-defensins. To understand the evolutionary dynamics of ?-defensin genes among primates, we identified the ?-defensin repertoires in human, chimpanzee, orangutan, macaque, and marmoset. The ?-defensin genes in primates can be classified into three phylogenetic classes (class I, II, and III). The presence of all three classes in the marmoset indicates that their divergence occurred before the separation of New World and Old World monkeys. Comparative analysis of the ?-defensin genomic clusters suggests that the makeup of the ?-defensin gene repertoires between primates is quite different, as their genes have undergone dramatic birth-and-death evolution. Analysis of the encoded peptides of the ?-defensin genes indicates that despite the overall high level of sequence divergence, certain amino acid residues or motifs are conserved within and between the three phylogenetic classes. The evolution of ?-defensins in primates, therefore, appears to be governed by two opposing evolutionary forces. One force stabilizes specific amino acid residues and motifs to preserve the functional and structural integrity of the molecules and the other diversifies the sequences generating molecules with a wide range of activities against a large number of pathogens.

SUBMITTER: Das S

PROVIDER: S-EPMC2981490 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Comparative genomics and evolution of the alpha-defensin multigene family in primates.

Das Sabyasachi S Nikolaidis Nikolas N Goto Hiroki H McCallister Chelsea C Li Jianxu J Hirano Masayuki M Cooper Max D MD

Molecular biology and evolution 20100509 10

Defensin genes encode small cationic antimicrobial peptides that form an important part of the innate immune system. They are divided into three families, alpha (α), beta (β), and theta (), according to arrangement of the disulfide bonding pattern between cysteine residues. Considering the functional importance of defensins, investigators have studied the evolution and the genomic organization of defensin genes. However, these studies have been restricted mainly to β-defensins. To understand the ...[more]

PMID: 20457584

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Project description:The primate ?-/?-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that ?-/?-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic ?-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid ?-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of ?-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.

Project description:DNA-binding transcription factors (TFs) are essential components of transcriptional regulatory networks in bacteria. LacI-family TFs (LacI-TFs) are broadly distributed among certain lineages of bacteria. The majority of characterized LacI-TFs sense sugar effectors and regulate carbohydrate utilization genes. The comparative genomics approaches enable in silico identification of TF-binding sites and regulon reconstruction. To study the function and evolution of LacI-TFs, we performed genomics-based reconstruction and comparative analysis of their regulons. For over 1300 LacI-TFs from over 270 bacterial genomes, we predicted their cognate DNA-binding motifs and identified target genes. Using the genome context and metabolic subsystem analyses of reconstructed regulons, we tentatively assigned functional roles and predicted candidate effectors for 78 and 67% of the analyzed LacI-TFs, respectively. Nearly 90% of the studied LacI-TFs are local regulators of sugar utilization pathways, whereas the remaining 125 global regulators control large and diverse sets of metabolic genes. The global LacI-TFs include the previously known regulators CcpA in Firmicutes, FruR in Enterobacteria, and PurR in Gammaproteobacteria, as well as the three novel regulators-GluR, GapR, and PckR-that are predicted to control the central carbohydrate metabolism in three lineages of Alphaproteobacteria. Phylogenetic analysis of regulators combined with the reconstructed regulons provides a model of evolutionary diversification of the LacI protein family. The obtained genomic collection of in silico reconstructed LacI-TF regulons in bacteria is available in the RegPrecise database (http://regprecise.lbl.gov). It provides a framework for future structural and functional classification of the LacI protein family and identification of molecular determinants of the DNA and ligand specificity. The inferred regulons can be also used for functional gene annotation and reconstruction of sugar catabolic networks in diverse bacterial lineages.

Project description:BackgroundHSP90 proteins are essential molecular chaperones involved in signal transduction, cell cycle control, stress management, and folding, degradation, and transport of proteins. HSP90 proteins have been found in a variety of organisms suggesting that they are ancient and conserved. In this study we investigate the nuclear genomes of 32 species across all kingdoms of organisms, and all sequences available in GenBank, and address the diversity, evolution, gene structure, conservation and nomenclature of the HSP90 family of genes across all organisms.ResultsTwelve new genes and a new type HSP90C2 were identified. The chromosomal location, exon splicing, and prediction of whether they are functional copies were documented, as well as the amino acid length and molecular mass of their polypeptides. The conserved regions across all protein sequences, and signature sequences in each subfamily were determined, and a standardized nomenclature system for this gene family is presented. The proeukaryote HSP90 homologue, HTPG, exists in most Bacteria species but not in Archaea, and it evolved into three lineages (Groups A, B and C) via two gene duplication events. None of the organellar-localized HSP90s were derived from endosymbionts of early eukaryotes. Mitochondrial TRAP and endoplasmic reticulum HSP90B separately originated from the ancestors of HTPG Group A in Firmicutes-like organisms very early in the formation of the eukaryotic cell. TRAP is monophyletic and present in all Animalia and some Protista species, while HSP90B is paraphyletic and present in all eukaryotes with the exception of some Fungi species, which appear to have lost it. Both HSP90C (chloroplast HSP90C1 and location-undetermined SP90C2) and cytosolic HSP90A are monophyletic, and originated from HSP90B by independent gene duplications. HSP90C exists only in Plantae, and was duplicated into HSP90C1 and HSP90C2 isoforms in higher plants. HSP90A occurs across all eukaryotes, and duplicated into HSP90AA and HSP90AB in vertebrates. Diplomonadida was identified as the most basal organism in the eukaryote lineage.ConclusionThe present study presents the first comparative genomic study and evolutionary analysis of the HSP90 family of genes across all kingdoms of organisms. HSP90 family members underwent multiple duplications and also subsequent losses during their evolution. This study established an overall framework of information for the family of genes, which may facilitate and stimulate the study of this gene family across all organisms.

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Comparative genomics and evolution of the alpha-defensin multigene family in primates.

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Comparative genomics and evolution of the alpha-defensin multigene family in primates.

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