Genetic and Developmental Implications for Trace Metal metabolism from Mutant and Inbred Strains of Animals
Owen M. Rennert, Wai-Yee Chan in Metabolism of Trace Metals in Man, 2017
It is unlikely that any such degree of redundancy would occur or, if it did, would give rise to a viable genotype for the whole organism. Nevertheless, gene duplication is the presumed phylogenetic basis for acquisition of gene redundancy, as is commonly understood for the myoglobin and hemoglobin genes; numerous other redundant structural genes, as well as the two MT genes, may have originated also by gene duplication. Although much is known about MT, the genetic map location of the MT structural genes is still unknown. This may be due principally to the fact that there are no known or easily identifiable isothionein differences within MT-1 or MT-2; the determination of linkage maps requires such identifiable differences and the observance of recombinations with other known chromosomal markers.
Radiogenomics
Jun Deng, Lei Xing in Big Data in Radiation Oncology, 2019
Thus, several computational approaches have been developed to narrow the space of possible hypotheses about potential protein function, followed by experimental/literature-based validation, thus expediting the overall process. The first natural approach was to use sequence homology assessment tools, such as the Basic Local Alignment Search Tool (BLAST) and Position-Specific Iterative BLAST (PSI-BLAST) (Altschul et al. 1990, 1997), to transfer functional annotations to unannotated proteins from proteins having similar amino acid sequences. However, other studies demonstrated that this approach does not always yield accurate results due to the multidomain structure of proteins and the insufficiency of sequence homology to reflect the effects of the evolutionary process of gene duplication (Gerlt and Babbitt 2000; Whisstock and Lesk 2003). Thus, a much wider spectrum of data types was leveraged to expand the types, specificity, and accuracy of protein functions that can be predicted. Appropriate data analysis methods, including those from machine learning (e.g., clustering, classification, and network analysis), were employed to infer protein function form these data types. Table 13.1 lists the most well-investigated data types, as well as the most prominent data analysis approaches, used to predict protein function. For details of these data types and approaches, we refer the reader to extensive reviews (Pandey et al. 2006; Lee et al. 2007; Sharan et al. 2007) and reports of recent large-scale assessments (Radivojac et al. 2013; Jiang et al. 2016).
Animal models for the study of innate immunity: protozoan infections in fish
G. F. Wiegertjes, G. Flik in Host-Parasite Interactions, 2004
We have found partial carp arginase cDNAs in a head kidney macrophage library and are presently sequencing the remainder of the cDNA sequences. Further, for fish, a number of expressed sequence tags for zebrafish (Danio rerio), rainbow trout (O. mykiss) and pufferfish (F. rubripes) arginase cDNAs are reported in the database. The fish cDNA sequences were used along with several invertebrate arginase and mammalian arginase-1 (liver form) and arginase-2 (extra-hepatic form) sequences to create a neighbour-joining tree. The fish arginases formed two separate clusters together with the mammalian arginase-1 and arginase-2 sequences (data not shown). Thus, the arginase gene duplication that gave rise to two arginase genes in the vertebrates likely occurred before the separation of vertebrates and invertebrates (Samson, 2000). Our findings that arginase in carp is expressed in head kidney macrophages suggests the existence of at least an extra-hepatic and functional arginase-2-like form in fish. In conclusion, teleost fish can be expected to have two arginase genes that likely encode for functional arginases that convert L-arginine to urea and ornithine but that are not centred on ammonia detoxification.
The therapeutic potential of RNA regulation in neurological disorders
Published in Expert Opinion on Therapeutic Targets, 2018
Jolien Roovers, Peter De Jonghe, Sarah Weckhuysen
Interference with alternative splicing can also be a potent strategy for treatment. An excellent example is spinomuscular atrophy (SMA), which is caused by recessive LOF mutations in SMN1. SMA is a hereditary disease that causes weakness and muscle wasting due to the loss of lower motor neurons [62]. A duplicate gene (SMN2) is a modifier of the disease, and having more copies of SMN2 results in a milder phenotype [63]. SMN2 is almost identical to SMN1 but produces less functional protein compared to SMN1, because of an alternative splicing event that removes exon 7 [64]. This results in 80–90% truncated non-functional protein, and only 10–20% full-length protein. By the end of 2016, the FDA approved nusinersen, the first therapy for SMA [27]. Nusinersen is a small 2ʹ-O-(2-methoxyethyl) modified ASO that binds the pre-mRNA of SMN2. It targets an intronic splicing silencer (ISS) in intron 7 of the SMN2 pre-mRNA, and displaces heterogenous nuclear ribonucleoproteins (hnRNPs) from this ISS. It thus facilitates accurate splicing of SMN2 transcripts [65–67], and promotes inclusion of exon 7, generating more functional protein and so compensating for the SMN1 loss.
Hematopoietic growth factors: the scenario in zebrafish
Published in Growth Factors, 2018
Vahid Pazhakh, Graham J. Lieschke
Gene duplication, not least in part the legacy of a whole genome duplication in the teleost radiation, has left its legacy on the zebrafish genome (Braasch et al., 2016; Postlethwait et al., 1998). While gene duplication can be considered to be an added complexity, it has also provided nature with an opportunity to explore biologically feasible variations that can provide biological insight when they are understood. Diversification processes including gene loss, subfunctionalization and neofunctionalization can eliminate or segregate biological functions between duplicates, or assign new functions to individual duplicates. These processes can create new private single ligand/receptor pairs, or regionally isolate components of promiscuous ligand/receptor groups to achieve highly specific anatomically-localized effects. Amongst model organisms, zebrafish are not unique in the diversity of their HGF ligand/receptor configurations: even between humans and mice, significant differences exist. For example, interleukin-3 receptor structure is more complex in the mouse than human, there being an extra mouse-specific alternative beta subunit (Geijsen et al., 2001; Hara & Miyajima, 1992).
Protein evolution revisited
Published in Systems Biology in Reproductive Medicine, 2018
Peter L. Davies, Laurie A. Graham
Sequencing of the first AFGP gene from an Antarctic notothenioid fish showed that it encoded 46 of the smallest AFGPs (each containing four of the Thr-Ala/Pro-Ala tripeptides repeated in tandem) as one large polyprotein (Hsiao et al. 1990). The AFGPs were separated within the polyprotein by a three-residue spacer Leu-Ile/Asn-Phe that was posttranslationally removed. Subsequently, sequencing of orthologous genes in another Antarctic notothenioid fish showed that the AFGP gene has been derived from a trypsinogen gene by gene duplication and divergence (Chen et al. 1997). In the process, almost all of the trypsinogen coding sequence was discarded. However, the two ends of the trypsinogen gene, including the signal sequence, are clearly recognizable in the AFGP gene and have experienced only single digit sequence divergence that suggests the gene arose ~10 ± 5 mya. The new AFGP coding region is derived from a short 9 bp segment at the end of an intron that became duplicated and amplified to code for the tandemly repeated Ala-Ala-Thr residue triplet. Conversely, the progenitor of the AFGP gene in cods appears to be noncoding DNA as the locus lacks similarity to trypsinogen or any other genic sequences (Baalsrud et al. 2018), so the derivation of this sequence has occurred independently of what evolved in the notothenioid fishes.
Related Knowledge Centers
- DNA
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- Polyploidy
- Aneuploidy
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