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).
Chloroplast DNA and Phylogenetic Relationships
S. K. Dutta in DNA Systematics, 2019
Several features of its evolution increase the systematic value of the chloroplast genome, particularly in comparison to the nuclear genome. Most nuclear genes in animals16,17,102–104 and in plants,105,106 even those once thought to be “single copy”, are actually members of small repeated gene families. A number of evolutionary processes such as gene duplication and deletion, concerted evolution, and pseudogene formation have been associated with such repeat families. All of these processes tend to distort the evolutionary history of DNA sequences relative to that of organisms. Therefore, particular care must be taken to understand as completely as possible the evolutionary history of a given nuclear gene and its family members before using sequence changes in these genes to imply organismal phylogeny. In contrast, there is no evidence that any of these processes occur in chloroplast DNA in such a way as to confound phylogenetic interpretation. The two repeat elements present in the only significant repeat family in angiosperm chloroplast genomes, i.e., the large inverted repeat discussed previously, do undergo concerted evolution, but this appears to occur so rapidly as to be unresolvable within interspecific19,21,24,28 and even laboratory107 time scales. The net result is that the two repeats evolve essentially as one genetic unit with a single, undistorted evolutionary history. The chloroplast genome is evolving quite slowly at the nucleotide sequence level.11–13,19,27,28,85,86 This fact, together with the absence of any mutational imbalances, such as the extreme transition-transversion bias found in animal mitochondrial DNA,14,15,108 is reflected by the extremely low incidence of parallel and convergent restriction site mutations found in studies at the interspecific level.19,23,28 Different portions of the chloroplast genome are evolving at different rates,11–13,85,86 thus providing a range of molecular yardsticks with which to measure evolutionary distances and determine relationships.
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).
Modern approaches for the phenotyping of cytochrome P450 enzymes in children
Published in Expert Review of Clinical Pharmacology, 2020
G. Magliocco, Y. Daali
CYP450 genotyping, including copy-number-variation analysis, is extensively used in clinical settings. It allows the identification of single nucleotide polymorphisms, gene deletion and gene duplication or multiplication. It requires DNA extraction from buccal swabs, saliva or blood and is therefore easily applicable in pediatrics. When available, it is then possible to translate the genotype of an isoenzyme into a phenotype using a standardized method as developed, for example, for the CYP2D6 enzyme by the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group [4]. Less standardized systems for translating genotype into phenotype also exist for CYP2B6, CYP2C9, CYP2C19 and CYP3A5 [4]. However, phenotype-genotype relationships are poorly described for CYP1A2 and CYP3A4 [3]. In addition, genotyping does not take into account the influence of environmental factors such as concomitant medication or smoking on the enzymatic activity. For these reasons, CYP450 phenotyping (i.e. real-time measurement of CYP450 activity) is therefore preferred to genotyping. In addition, it allows the evolution of these enzymes over time and age to be captured [2,5].
Serine-rich repeat proteins from gut microbes
Published in Gut Microbes, 2020
Dimitrios Latousakis, Donald A. MacKenzie, Andrea Telatin, Nathalie Juge
The glycosylation profile of SRRPs from L. reuteri was recently determined using a combination of bioinformatics analysis, lectin screening, LC-MS-based sugar nucleotide profiling, MALDI-ToF, and GC-MS analyses. This study showed that the L. reuteri ATCC 53608 and 100-23C strains were capable of performing protein glycosylation and that SRRP100-23 and SRRP53608 were glycosylated with Hex-Hex-HexNAc and di-HexNAc moieties, respectively. Following in vivo glycoengineering in E. coli, NMR analysis and enzymatic treatment further showed that SRRP53608 was glycosylated with GlcNAcβ(1→6)-GlcNAcα moieties. Together, it was suggested that SRRP100-23 is glycosylated with GlcNAc and Hex-Glc-GlcNAc whereas SRRP53608 is glycosylated with GlcNAc and di-GlcNAc moieties15 (Figure 4) (Table 1). Although both strains encode a predicted Asp2, O-acetylation could not be confirmed biochemically due to the conditions used in the MS analysis.15 The number of GTs in the L. reuteri 100-23C SecA2/Y2 cluster exceeds the number of sugars on SRRP100-23, as also reported for some streptococcal SecA2/Y2 systems.14,45 To date, there is no generic explanation for the presence of additional genes encoding GTs in the genomes of these strains. In some cases, gene duplication is observed, which may lead to functional redundancy, whereas insertion of genetic elements into genes encoding GTs may lead to gene inactivation. A defective glycosylation of SRRPs in pathogenic bacteria led to impaired binding of the respective bacteria onto model substrates and reduced virulence in mouse models.1,55,56 The glycosylation of SRRPs in Lactobacillus species, as demonstrated for L. reuteri strains, is likely to impact on the adhesion capacity of these strains.
Related Knowledge Centers
- DNA
- DNA Repair
- DNA Replication
- Molecular Evolution
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- Slipped Strand Mispairing
- Polyploidy
- Aneuploidy
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