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51.
The interaction between mobile DNA sequences and their hosts raises important questions in the context of hosts which reproduce clonally with only rare horizontal transmission between clones. The activity of some mobile DNAs as reversible mutators of genes raises the possibility that, in a fluctuating environment, cells may gain an advantage if they have mobile DNAs which mutate genes whose inactivation is favoured in one of the environments that the population encounters. Here we analyse a model of this process and ask what would be the optimal rate of transposition in a population whose elements are maintained by this mechanism. We also examine the impact of horizontal transfer on such a population. With movement of elements between cells, we can imagine elements with differing rates of transposition and host cells with differing rates of transposition. We find that evolution in the population of elements favours a rapid rate of transposition, and evolution of the host cells favours cells in which this rapid rate of element-dependent transposition results in an optimal rate of transposition per cell. However, when horizontal transfer rates are high, some unexpected features of the model are observed. In particular, a polymorphism between cell types (some with an optimal rate of transposition and some with no transposition at all from endogenous elements) can be stably maintained. We consider the possible biological predictions of this analysis. 相似文献
52.
《Journal of molecular biology》2021,433(22):167252
Human γD-crystallin (HGD) has remarkable stability against condensation in the human lens, sometimes over a whole lifetime. The native protein has a surface exposed free cysteine that forms dimers (Benedek, 1997; Ramkumar et al., 1864)1,2 without specific biological function and leads to further protein association and/or aggregation, which creates a paradox for understanding its stability. Previous work has demonstrated that chemical modification of the protein at the free cysteine (C110), increases the temperature at which liquid–liquid phase separation occurs (LLPS), lowers protein solubility and suggests an important role for this amino acid in maintaining its long-term resistance to condensation. Here we demonstrate that mutation of the cysteine does not alter the structure or solubility (liquidus) line for the protein, but dramatically increases the protein crystal nucleation rate following LLPS, suggesting that the free cysteine has a vital role in suppressing crystallization in the human lens. 相似文献
53.
Xin-Jia Wang Spencer C H Barrett Li Zhong Zhi-Kun Wu De-Zhu Li Hong Wang Wei Zhou 《Molecular biology and evolution》2021,38(1):168
The evolutionary transition from outcrossing to selfing can have important genomic consequences. Decreased effective population size and the reduced efficacy of selection are predicted to play an important role in the molecular evolution of the genomes of selfing species. We investigated evidence for molecular signatures of the genomic selfing syndrome using 66 species of Primula including distylous (outcrossing) and derived homostylous (selfing) taxa. We complemented our comparative analysis with a microevolutionary study of P. chungensis, which is polymorphic for mating system and consists of both distylous and homostylous populations. We generated chloroplast and nuclear genomic data sets for distylous, homostylous, and distylous–homostylous species and identified patterns of nonsynonymous to synonymous divergence (dN/dS) and polymorphism (πN/πS) in species or lineages with contrasting mating systems. Our analysis of coding sequence divergence and polymorphism detected strongly reduced genetic diversity and heterozygosity, decreased efficacy of purifying selection, purging of large-effect deleterious mutations, and lower rates of adaptive evolution in samples from homostylous compared with distylous populations, consistent with theoretical expectations of the genomic selfing syndrome. Our results demonstrate that self-fertilization is a major driver of molecular evolutionary processes with genomic signatures of selfing evident in both old and relatively young homostylous populations. 相似文献
54.
D. Li I. Barclay K. Jose K. Stefanova R. Appels 《Molecular breeding : new strategies in plant improvement》2008,22(2):217-225
A new mutation at the acetohydroxyacid synthase (AHAS) locus on chromosome 6D of wheat was analyzed in detail because it conferred
an improved resistance to the imidazolinone group of herbicides. Sequence analysis showed that the mutation was at the Ala122
position (A122T), a position in AHAS which has not to date been identified in imidazolinone resistant wheat lines even though
the position has been identified in other plants and is associated with resistance. An allele-specific assay for the mutation
(in the wheat line Brookton-8) was developed and used in a genetic analysis. Two mapping populations were analysed and the
doubled haploid progeny from the cross Brookton-8 × Clearfield STL proved to be most informative. The AHASAla122 mutation (A122T) was allelic to the AHASSer653 mutation (S653N) in Clearfield STL (Imi1, on chromosome 6D) and hence was assigned to the chromosome 6D locus. The analysis
of the doubled haploid lines in the mapping population demonstrated the greater resistance conferred by the A122T mutation
because lines from the same cross and carrying either the A122T or S653N mutations could be directly compared.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
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57.
《MABS-AUSTIN》2013,5(1):57-68
An immunotoxin (IT) constructed with RFB4, a murine anti-CD22 monoclonal antibody, and the “deglycosylated” A chain of ricin has shown activity at safe doses in patients with non-Hodgkin lymphoma and in children with acute lymphoblastic leukemia. The dose limiting toxicity is vascular leak syndrome (VLS), which appears to be due to a unique amino acid motif in the ricin toxin A (RTA) chain that damages vascular endothelial cells. We mutated recombinant (r) RTA to disable this site, but await testing of the IT prepared with this mutant RTA in humans. Another possible approach to reducing IT-induced VLS is to shorten the half-life of the IT in vivo. We previously constructed a mouse-human chimeric RFB4 by grafting the variable genes of RFB4 onto the human IgG1k constant regions. Here, we report the expansion of our panel of mutant chimeric RFB4s (mcRFB4s) that lack the ability to bind to the neonatal Fc receptor (FcRn). In comparison with cRFB4, which had a T1/2 of 263 h, the mcRFB4s had T1/2s ranging from 39 to 106 h. ITs were constructed with these mcRFB4s and rRTA. The mcRFB4-RTA ITs retained their cytotoxicity in vitro and had shorter half lives than the parental cRFB4-RTA IT. In addition, the mcRFB4 IT with the shortest T1/2 induced less pulmonary vascular leak in mice, which we have postulated is a surrogate marker for VLS in humans. 相似文献
58.
Anil K. Bidwai Cassandra MeyenHeather Kilheeney Damian WroblewskiLidia B. Vitello James E. Erman 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(1):137-148
Three yeast cytochrome c peroxidase (CcP) variants with apolar distal heme pockets have been constructed. The CcP variants have Arg48, Trp51, and His52 mutated to either all alanines, CcP(triAla), all valines, CcP(triVal), or all leucines, CcP(triLeu). The triple mutants have detectable enzymatic activity at pH 6 but the activity is less than 0.02% that of wild-type CcP. The activity loss is primarily due to the decreased rate of reaction between the triple mutants and H2O2 compared to wild-type CcP. Spectroscopic properties and cyanide binding characteristics of the triple mutants have been investigated over the pH stability region of CcP, pH 4 to 8. The absorption spectra indicate that the CcP triple mutants have hemes that are predominantly five-coordinate, high-spin at pH 5 and six-coordinate, low-spin at pH 8. Cyanide binding to the triple mutants is biphasic indicating that the triple mutants have two slowly-exchanging conformational states with different cyanide affinities. The binding affinity for cyanide is reduced at least two orders of magnitude in the triple mutants compared to wild-type CcP and the rate of cyanide binding is reduced by four to five orders of magnitude. Correlation of the reaction rates of CcP and 12 distal pocket mutants with H2O2 and HCN suggests that both reactions require ionization of the reactants within the distal heme pocket allowing the anion to bind the heme iron. Distal pocket features that promote substrate ionization (basic residues involved in base-catalyzed substrate ionization or polar residues that can stabilize substrate anions) increase the overall rate of reaction with H2O2 and HCN while features that inhibit substrate ionization slow the reactions. 相似文献
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