The chicken IL-1 family: evolution in the context of the studied vertebrate lineage

The interleukin-1 gene family encodes a group of related proteins that exhibit a remarkable pleiotropy in the context of health and disease. The set of indispensable functions they control suggests that these genes should be found in all eukaryotic species. The ligands and receptors of this family have been primarily characterised in man and mouse. The genomes of most non-mammalian animal species sequenced so far possess all of the IL-1 receptor genes found in mammals. Yet, strikingly, very few of the ligands are identifiable in non-mammalian genomes. Our recent identification of two further IL-1 ligands in the chicken warranted a critical reappraisal of the evolution of this vitally important cytokine family. This review presents substantial data gathered across multiple, divergent metazoan genomes to unambiguously trace the origin of these genes. With the hypothesis that all of these genes, both ligands and receptors, were formed in a single ancient ancestor, extensive database mining revealed sufficient evidence to confirm this. It therefore suggests that the emergence of mammals is unrelated to the expansion of the IL-1 family. A thorough review of this cytokine family in the chicken, the most extensively studied amongst non-mammalian species, is also presented.     

Molecular evolution and expression pattern of Toll-like receptor 3 from the lamprey Lampetra japonica

Toll-like receptors(TLRs)are type I transmembrane proteins that are important components of innate immunity and play essential roles in inducing acquired immune responses[1].These proteins consist of three parts:the cytoplasmic domain,transmembrane domain,and extracellular domain.The extracellular domain is composed of 18–33 leucine-rich repeat(LRR)sequences that enable the host to specifically recognize pathogen-associated molecular patterns and are the core of TLR recognition ligands[2].The cytoplasmic domain is homologous with the interleukin 1 receptor(IL-1R)family and known as the Toll-IL-1 receptor homology domain,which is highly conserved and plays a key role in signal transduction[1].TLR3 recognizes viral dsRNA during immune protection from viruses[3].After the host is infected by a virus,the LRR region of TLR3 recognizes the viral dsRNA,and the Toll/IL-1 receptor(TIR)domain recruits the adaptor protein TIR domain-containing molecule 1(also known as TRIF)for signal cascade transmission[4].The activation of TLR3 finally leads to cytokine secretion,especially the production of type I interferon[4].Lamprey,the most primitive marine jawless vertebrate,is an ideal model for studying vertebrate embryo development,organ differentiation,and immune system evolution[5].Although jawless vertebrates contain three variable lymphocyte receptors,they have not been found to possess the recombinational antigen receptors shared by all jawed vertebrates[6].Compared with that in higher vertebrates,the mechanism of acquired immunity in lampreys is still not complete,and lampreys rely mainly on innate immunity to fight against pathogenic microorganisms.Although TLR3 has been extensively studied in jawed vertebrates,little is known about the molecular evolutionary history and expression patterns of TLR3 in jawless vertebrates.     

Cloning and analysis of an HMG gene from the lamprey Lampetra fluviatilis: gene duplication in vertebrate evolution

Evolution has shaped the organisation of vertebrate genomes, including the human genome. To shed further light on genome history, we have cloned and analysed an HMG gene from lamprey, representing one of the earliest vertebrate lineages. Genes of the HMG1/2 family encode chromosomal proteins that bind DNA in a non-sequence-specific manner, and have been implicated in a variety of cellular processes dependent on chromatin structure. They are characterised by two copies of a conserved motif, the HMG box, followed by an acidic C-terminal region. We report here the cloning of a cDNA clone from the river lamprey Lampetra fluviatilis containing a gene with two HMG boxes and an acidic tail; we designate this gene LfHMG1. Molecular phylogenetic analysis shows that LfHMG1 is descended from a gene ancestral to mammalian HMG1 and HMG2. This implies that there was a duplication event in the HMG1/2 gene family, that occurred after the divergence of the jawed and jawless fishes, 450 million years ago. This conclusion supports and refines the hypothesis that there was a period of extensive gene duplication early in vertebrate evolution. We also show that the HMG1/2 family originated before the protostomes and deuterostomes diverged, over 525 million years ago.     

Phylogenetic analysis of the tenascin gene family: evidence of origin early in the chordate lineage

Background  

Tenascins are a family of glycoproteins found primarily in the extracellular matrix of embryos where they help to regulate cell proliferation, adhesion and migration. In order to learn more about their origins and relationships to each other, as well as to clarify the nomenclature used to describe them, the tenascin genes of the urochordate Ciona intestinalis, the pufferfish Tetraodon nigroviridis and Takifugu rubripes and the frog Xenopus tropicalis were identified and their gene organization and predicted protein products compared with the previously characterized tenascins of amniotes.     

The sea lamprey Petromyzon marinus genome reveals the early origin of several chemosensory receptor families in the vertebrate lineage

Background  

In gnathostomes, chemosensory receptors (CR) expressed in olfactory epithelia are encoded by evolutionarily dynamic gene families encoding odorant receptors (OR), trace amine-associated receptors (TAAR), V1Rs and V2Rs. A limited number of OR-like sequences have been found in invertebrate chordate genomes. Whether these gene families arose in basal or advanced vertebrates has not been resolved because these families have not been examined systematically in agnathan genomes.     

Evolutionary genetics of vertebrate tissue mineralization: the origin and evolution of the secretory calcium-binding phosphoprotein family

Three principal mineralized tissues are present in teeth; a highly mineralized surface layer (enamel or enameloid), body dentin, and basal bone. Similar tissues have been identified in the dermal skeleton of Paleozoic jawless vertebrates, suggesting their ancient origin. These dental tissues form on protein matrix and their mineralization is controlled by distinctive proteins. We have shown that many secretory calcium-binding phosphoproteins (SCPPs) are involved in tetrapod tissue mineralization. These SCPPs all originated from the common ancestral gene SPARCL1 (secreted protein, acidic, cysteine-rich like 1) that initially arose from SPARC. The SCPP family also includes a bird eggshell matrix protein, mammalian milk casein, and salivary proteins. The eggshell SCPP plays crucial roles in rigid eggshell production, milk SCPPs in efficient lactation and in the evolution of complex dentition, and salivary SCPPs in maintaining tooth integrity. A comparative analysis of the mammalian, avian, and amphibian genomes revealed a tandem duplication history of the SCPP genes in tetrapods. Although these tetrapod SCPP genes are fewer in teleost genomes, independent parallel duplication has created distinct SCPP genes in this lineage. These teleost SCPPs are also used for enameloid and dentin mineralization, implying essential roles of SCPPs for dental tissue mineralization in osteichthyans. However, the SCPPs used for tetrapod enamel and teleost enameloid, as well as tetrapod dentin and teleost dentin, are all different. Thus, the evolution of vertebrate mineralized tissues seems to be explained by phenogenetic drift: while mineralized tissues are retained during vertebrate evolution, the underlying genetic basis has extensively drifted.     

Comparative genomic analysis of mammalian NKG2D ligand family genes provides insights into their origin and evolution

NKG2D is a major activating receptor of natural killer cells. Its ligands are major histocompatibility complex (MHC) class I-like molecules whose expression is induced by cellular stresses such as infections and tumorigenesis. Humans have two families of NKG2D ligands (NKG2DL): MHC class I-related chains (MIC) encoded in the MHC and UL16-binding proteins (ULBP) encoded outside the MHC. By contrast, mice have only the latter family of ligands; instead, they have non-MHC-encoded MILL molecules that are closely related to MIC, but do not function as NKG2DL. To gain insights into the origin and evolution of MIC, ULBP, and MILL gene families, we conducted comparative genomic analysis of NKG2DL family genes in five mammalian species. In the opossum MHC, we identified a ULBP-like gene adjacent to a previously described MIC-like gene, suggesting that ULBP genes were originally encoded in the MHC. The opossum genome also contained a transcribed MILL-like gene in a region syntenic to the rodent regions encoding MILL molecules. These observations indicate that MIC-, ULBP-, and MILL-like genes emerged before the divergence of placental and marsupial mammals. Comparison of the human, cattle, rat, mouse, and opossum genomes indicates that after emigration from the MHC, ULBP genes underwent extensive duplications in each species. In mice, some of the ULBP genes appear to have been translocated telomerically on the same chromosome, forming a major cluster of existent NKG2DL genes.     

Retroviral and pseudogene insertion sites reveal the lineage of human salivary and pancreatic amylase genes from a single gene during primate evolution.

We have analyzed the junction regions of inserted elements within the human amylase gene complex. This complex contains five genes which are expressed at high levels either in the pancreas or in the parotid gland. The proximal 5'-flanking regions of these genes contain two inserted elements. A gamma-actin pseudogene is located at a position 200 base pairs upstream of the first coding exon. All of the amylase genes contain this insert. The subsequent insertion of an endogenous retrovirus interrupted the gamma-actin pseudogene within its 3'-untranslated region. Nucleotide sequence analysis of the inserted elements associated with each of the five human amylase genes has revealed a series of molecular events during the recent history of this gene family. The data indicate that the entire gene family was generated during primate evolution from one ancestral gene copy and that the retroviral insertion activated a cryptic promoter.     

The molecular evolution of the vertebrate behavioural repertoire

How the sophisticated vertebrate behavioural repertoire evolved remains a major question in biology. The behavioural repertoire encompasses the set of individual behavioural components that an organism uses when adapting and responding to changes in its external world. Although unicellular organisms, invertebrates and vertebrates share simple reflex responses, the fundamental mechanisms that resulted in the complexity and sophistication that is characteristic of vertebrate behaviours have only recently been examined. A series of behavioural genetic experiments in mice and humans support a theory that posited the importance of synapse proteome expansion in generating complexity in the behavioural repertoire. Genome duplication events, approximately 550 Ma, produced expansion in the synapse proteome that resulted in increased complexity in synapse signalling mechanisms that regulate components of the behavioural repertoire. The experiments demonstrate the importance to behaviour of the gene duplication events, the diversification of paralogues and sequence constraint. They also confirm the significance of comparative proteomic and genomic studies that identified the molecular origins of synapses in unicellular eukaryotes and the vertebrate expansion in proteome complexity. These molecular mechanisms have general importance for understanding the repertoire of behaviours in different species and for human behavioural disorders arising from synapse gene mutations.     

Origin and evolution of vertebrate ABCA genes: a story from amphioxus

Previous studies showed that the vertebrate ABCA subfamily, one subgroup of the ATP-binding-cassette superfamily, has evolved rapidly in terms of gene duplication and loss. To further uncover the evolutionary history of the ABCA subfamily, we characterized ABCA members of two amphioxus species (Branchiostoma floridae and B. belcheri), the closest living invertebrate relative to vertebrates. Phylogenetic analysis indicated that these two species have the same set of ABCA genes (both containing six members). Five of these genes have clear orthologs in vertebrate, including one cephalochordate-specific duplication and one vertebrate-specific duplication. In addition, it is found that human orthologs of amphioxus ABCA1/4/7 and its neighboring genes mainly localize on chromosome 1, 9, 19 and 5. Considering that most of analyzed amphioxus genes have clear orthologs in zebrafish, we conclude these four human paralogous regions might derive from a common ancestral region by genome duplication occurred prior to teleost/tetrapod split. Therefore, the present results provide new evidence for 2R hypothesis.     

Zebra fish myc family and max genes: differential expression and oncogenic activity throughout vertebrate evolution.

To gain insight into the role of Myc family oncoproteins and their associated protein Max in vertebrate growth and development, we sought to identify homologs in the zebra fish (Brachydanio rerio). A combination of a polymerase chain reaction-based cloning strategy and low-stringency hybridization screening allowed for the isolation of zebra fish c-, N-, and L-myc and max genes; subsequent structural characterization showed a high degree of conservation in regions that encode motifs of known functional significance. On the functional level, zebra fish Max, like its mammalian counterpart, served to suppress the transformation activity of mouse c-Myc in rat embryo fibroblasts. In addition, the zebra fish c-myc gene proved capable of cooperating with an activated H-ras to effect the malignant transformation of mammalian cells, albeit with diminished potency compared with mouse c-myc. With respect to their roles in normal developing tissues, the differential temporal and spatial patterns of steady-state mRNA expression observed for each zebra fish myc family member suggest unique functions for L-myc in early embryogenesis, for N-myc in establishment and growth of early organ systems, and for c-myc in increasingly differentiated tissues. Furthermore, significant alterations in the steady-state expression of zebra fish myc family genes concomitant with relatively constant max expression support the emerging model of regulation of Myc function in cellular growth and differentiation.     

Domain combination of the vertebrate-like TLR gene family: implications for their origin and evolution

Domain shuffling, which is an important mechanism in the evolution of multi-domain proteins, has shaped the evolutionary development of the immune system in animals. Toll and Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate and adaptive immune systems. Draft genome sequences provide the opportunity to compare the Toll/TLR gene repertoire among representative metazoans. In this study, we investigated the combination of Toll/interleukin-1 receptor (TIR) and leucine-rich repeat (LRR) domains of metazoan Toll/TLRs. Before Toll with both domains occurred in Cnidaria (sea anemone, Nematostella vectensis), through domain combinations, TIR-only and LRR-only proteins had already appeared in sponges (Amphimedon queenslandica). Although vertebrate-like TIR (V-TIR) domain already appeared in Cnidaria, the vertebrate-like TLR (V-TLR) with both domains appeared much later. The first combination between V-TIR domain and vertebrate-like LRR (V-LRR) domain for V-TLR may have occurred after the divergence of Cnidaria and bilateria. Then, another combination for V-TLR, a recombination of both domains, possibly occurred before or during the evolution of primitive vertebrates. Taken together, two rounds of domain combinations may thus have co-shaped the vertebrate TLRs.     

Extensive duplications of phototransduction genes in early vertebrate evolution correlate with block (chromosome) duplications

Many gene families in mammals have members that are expressed more or less uniquely in the retina or differentially in specific retinal cell types. We describe here analyses of nine such gene families with regard to phylogenetic relationships and chromosomal location. The families are opsins, G proteins (alpha, beta, and gamma subunits), phosphodiesterases type 6, cyclic nucleotide-gated channels, G-protein-coupled receptor kinases, arrestins, and recoverins. The results suggest that multiple new gene copies arose in all of these families very early in vertebrate evolution during a period with extensive gene duplications. Many of the new genes arose through duplications of large chromosome regions (blocks of genes) or even entire chromosomes, as shown by linkage with other gene families. Some of the phototransduction families belong to the same duplicated regions and were thus duplicated simultaneously. We conclude that gene duplications in early vertebrate evolution probably helped facilitate the specialization of the retina and the subspecialization of different retinal cell types.     

The evolution of milk casein genes from tooth genes before the origin of mammals

Caseins are among cardinal proteins that evolved in the lineage leading to mammals. In milk, caseins and calcium phosphate (CaP) form a huge complex called casein micelle. By forming the micelle, milk maintains high CaP concentrations, which help altricial mammalian neonates to grow bone and teeth. Two types of caseins are known. Ca-sensitive caseins (α(s)- and β-caseins) bind Ca but precipitate at high Ca concentrations, whereas Ca-insensitive casein (κ-casein) does not usually interact with Ca but instead stabilizes the micelle. Thus, it is thought that these two types of caseins are both necessary for stable micelle formation. Both types of caseins show high substitution rates, which make it difficult to elucidate the evolution of caseins. Yet, recent studies have revealed that all casein genes belong to the secretory calcium-binding phosphoprotein (SCPP) gene family that arose by gene duplication. In the present study, we investigated exon-intron structures and phylogenetic distributions of casein and other SCPP genes, particularly the odontogenic ameloblast-associated (ODAM) gene, the SCPP-Pro-Gln-rich 1 (SCPPPQ1) gene, and the follicular dendritic cell secreted peptide (FDCSP) gene. The results suggest that contemporary Ca-sensitive casein genes arose from a putative common ancestor, which we refer to as CSN1/2. The six putative exons comprising CSN1/2 are all found in SCPPPQ1, although ODAM also shares four of these exons. By contrast, the five exons of the Ca-insensitive casein gene are all reminiscent of FDCSP. The phylogenetic distribution of these genes suggests that both SCPPPQ1 and FDCSP arose from ODAM. We thus argue that all casein genes evolved from ODAM via two different pathways; Ca-sensitive casein genes likely originated directly from SCPPPQ1, whereas the Ca-insensitive casein genes directly differentiated from FDCSP. Further, expression of ODAM, SCPPPQ1, and FDCSP was detected in dental tissues, supporting the idea that both types of caseins evolved as Ca-binding proteins. Based on these findings, we propose two alternative hypotheses for micelle formation in primitive milk. The conserved biochemical characteristics in caseins and their immediate ancestors also suggest that many slight genetic modifications have created modern caseins, proteins vital to the sustained success of mammals.