Fugu: a compact vertebrate reference genome Venkatesh, Byrappa; Gilligan, Patrick; Brenner, Sydney
FEBS Letters,
June 30, 2000, Letnik:
476, Številka:
1
Book Review, Journal Article
Recenzirano
Odprti dostop
At 400 Mb, the Japanese pufferfish,
Fugu rubripes, has the smallest vertebrate genome but has a similar gene repertoire to other vertebrates. Its genes are densely packed with short intergenic and ...intronic sequences devoid of repetitive elements. It likely has a mutational bias towards DNA elimination and is probably close to a ‘minimal’ vertebrate genome. As such it is a useful reference genome for gene discovery and gene validation in other vertebrates. Its usefulness in the discovery of conserved regulatory elements has already been demonstrated. The Fugu genome sequence is a good complement to genetic studies in other vertebrates.
Non-visual photoreception in mammals is primarily mediated by two splice variants that derive from a single melanopsin (OPN4M) gene, whose expression is restricted to a subset of retinal ganglion ...cells. Physiologically, this sensory system regulates the photoentrainment of many biological rhythms, such as sleep via the melatonin endocrine system and pupil constriction. By contrast, melanopsin exists as two distinct lineages in non-mammals, opn4m and opn4x, and is broadly expressed in a wide range of tissue types, including the eye, brain, pineal gland and skin. Despite these findings, the evolution and function of melanopsin in early vertebrates are largely unknown. We, therefore, investigated the complement of opn4 classes present in the genome of a model deep-sea cartilaginous species, the elephant shark (Callorhinchus milii), as a representative vertebrate that resides at the base of the gnathostome (jawed vertebrate) lineage. We reveal that three melanopsin genes, opn4m1, opn4m2 and opn4x, are expressed in multiple tissues of the elephant shark. The two opn4m genes are likely to have arisen as a result of a lineage-specific duplication, whereas "long" and "short" splice variants are generated from a single opn4x gene. By using a heterologous expression system, we suggest that these genes encode functional photopigments that exhibit both "invertebrate-like" bistable and classical "vertebrate-like" monostable biochemical characteristics. We discuss the evolution and function of these melanopsin pigments within the context of the diverse photic and ecological environments inhabited by this chimaerid holocephalan, as well as the origin of non-visual sensory systems in early vertebrates.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Somatosensory tinnitus (ST) is associated with activation of the auditory pathway by trigeminal or cervical afferents. Objective This is a cross‐sectional observational study that ...aims to verify the association of ST with TMD, bruxism, migraine and psychosocial aspects. Methods This study was conducted at the Tinnitus Outpatient Clinic of the Clinical Hospital Complex of the Federal University of Paraná. Specific ST characteristics, were evaluated according to the last consensus for the diagnosis of ST. Two groups with 39 individuals each one were formed, the ST group (STG) and the comparison group (CG). TMD was classified according to the Diagnostic Criteria for Temporomandibular Disorders and migraine by the International Classification of Headaches. The presence of probable sleep and awake bruxism was associated with individual's reports and clinical inspections. The applied questionnaires investigated oral behaviours (OB), sleep quality (SQ), psychosocial aspects (PA), central sensitization (CS), tinnitus impact on quality of life (TIQF), and graded chronic pain scale (GCPS). Results The STG showed a significant association with modulation manoeuvres and trigger points; myalgias and arthralgia; disc displacement with and without reduction; subluxation; bruxism; and presence of migraine. For the same group, we found a significant association with OB, PA, CS, TIQF and GCPS. There was no significant difference between groups regarding SQ. Conclusion There is a significant association between the presence of ST and the occurrence of TMD, probable sleep and awake bruxism, and migraine. There is also a greater impairment of OB, PA, CS and TIQF.
Tetrodotoxin (TTX) is a highly potent neurotoxin that selectively binds to the outer vestibule of voltage-gated sodium channels. Pufferfishes accumulate extremely high concentrations of TTX without ...any adverse effect. A nonaromatic amino acid (Asn) residue present in domain I of the pufferfish,
Takifugu pardalis, Na
v1.4 channel has been implicated in the TTX resistance of pufferfishes
1. However, the effect of this residue on TTX sensitivity has not been investigated, and it is not known if this residue is conserved in all pufferfishes. We have investigated the genetic basis of TTX resistance in pufferfishes by comparing the sodium channels from two pufferfishes (
Takifugu rubripes fugu and
Tetraodon nigroviridis) and the TTX-sensitive zebrafish. Although all three fishes contain duplicate copies of Na
v1.4 channels (Na
v1.4a and Na
v1.4b), several substitutions were found in the TTX binding outer vestibule of the two pufferfish channels. Electrophysiological studies showed that the nonaromatic residue (Asn in fugu and Cys in
Tetraodon) in domain I of Na
v1.4a channels confers TTX resistance. The Glu-to-Asp mutation in domain II of
Tetraodon channel Na
v1.4b is similar to that in the saxitoxin- and TTX-resistant Na
+ channels of softshell clams
2. Besides helping to deter predators, TTX resistance enables pufferfishes to selectively feed on TTX-bearing organisms.
In this paper we report the cloning and characterization of the erythropoietin(Epo)gene from the pufferfish,Fugu rubripes.This is the first nonmammalianEpogene to be cloned. The FuguEpocomprises 5 ...exons and 4 introns similar to the humanEPO,and encodes a 185–amino acid protein that is 32% to 34% identical to Epo from various mammals. The synteny of genes at theEpolocus is conserved between the Fugu and humans. Unlike in mammals in which adult kidney is the primary Epo-producing organ, the heart is the main Epo-producing organ in adult Fugu. In addition to the heart, FuguEpois also expressed in the liver and brain similar to the humanEPO.Interestingly, the transcripts in the Fugu brain are generated from a distal promoter and include an alternatively spliced first coding exon. No such brain-specific alternative splicing of Epo has been reported in mammals so far. Transient transfection studies in a fish hepatoma cell line (PLHC-1) and a human hepatoma cell line (HepG2) suggest that although the FuguEpopromoter many not be hypoxia inducible, the gene may be regulated by hypoxia.
Protein tyrosine kinases (PTKs) play a critical role in the manifestation of cancer cell properties, and respective signaling mechanisms have been studied extensively on immortalized tumor cells. To ...characterize and analyze commonly used cancer cell lines with regard to variations in the primary structure of all expressed PTKs, we conducted a cDNA-based sequence analysis of the entire tyrosine kinase transcriptome of 254 established tumor cell lines. The profiles of cell line intrinsic PTK transcript alterations and the evaluation of 155 identified polymorphisms and 234 somatic mutations are made available in a database designated "Tykiva" (tyrosine kinome variant). Tissue distribution analysis and/or the localization within defined protein domains indicate functional relevance of several genetic alterations. The cysteine replacement of the highly conserved Y367 residue in fibroblast growth factor receptor 4 or the Q26X nonsense mutation in the tumor-suppressor kinase CSK are examples, and may contribute to cell line-specific signaling characteristics and tumor progression. Moreover, known variants, such as epidermal growth factor receptor G719S, that were shown to mediate anticancer drug sensitivity could be detected in other than the previously reported tumor types. Our data therefore provide extensive system information for the design and interpretation of cell line-based cancer research, and may stimulate further investigations into broader clinical applications of current cancer therapeutics.
“… We envisioned an iterative system where a unique DNA tag identifier that encoded the event was appended to each newly formed molecule. These vast collections of molecules are known today as DNA‐ ...encoded chemical libraries (DECLs), and allow scientists to do selections on the benchtop that previously required access to large and complex high‐throughput screening centers …” Read more in the Guest Editorial by Richard A. Lerner and Sydney Brenner.
The advent of techniques for cloning and rapidly sequencing DNA has produced an explosive increase of sequence information for nucleic acids and their inferred proteins. Careful study of this large ...store of data might give us new insights into the relations between the linear sequences of genes and their functions embodied in the three-dimensional structure of proteins, and also illuminate the origin and evolution of the structural complexity of present-day proteins. Here I argue from such a study that the active site sequences of enzymes that have analogous essential serine residues lie in fact on two lines of descent from an ancient ancestral enzyme which had a cysteine instead of serine in its active site. This is based on the assumption that the two codon types which define the separate lines of descent and which have different bases in two positions could not interconvert by single mutations.
Cartilaginous fishes are the oldest living phylogenetic group of jawed vertebrates. Here, we demonstrate the value of cartilaginous fish sequences in reconstructing the evolutionary history of ...vertebrate genomes by sequencing the protocadherin cluster in the relatively small genome (910 Mb) of the elephant shark (Callorhinchus milii). Human and coelacanth contain a single protocadherin cluster with 53 and 49 genes, respectively, that are organized in three subclusters, Pcdhα, Pcdhβ, and Pcdhγ, whereas the duplicated protocadherin clusters in fugu and zebrafish contain >77 and 107 genes, respectively, that are organized in Pcdhα and Pcdhγ subclusters. By contrast, the elephant shark contains a single protocadherin cluster with 47 genes organized in four subclusters (Pcdhδ, Pcdhε, Pcdhμ, and Pcdhν). By comparison with elephant shark sequences, we discovered a Pcdhδ subcluster in teleost fishes, coelacanth, Xenopus, and chicken. Our results suggest that the protocadherin cluster in the ancestral jawed vertebrate contained more subclusters than modern vertebrates, and the evolution of the protocadherin cluster is characterized by lineage-specific differential loss of entire subclusters of genes. In contrast to teleost fish and mammalian protocadherin genes that have undergone gene conversion events, elephant shark protocadherin genes have experienced very little gene conversion. The syntenic block of genes in the elephant shark protocadherin locus is well conserved in human but disrupted in fugu. Thus, the elephant shark genome appears to be less prone to rearrangements compared with teleost fish genomes. The small and "stable" genome of the elephant shark is a valuable reference for understanding the evolution of vertebrate genomes.
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