A general method for identifying correct solutions in the quantitative analysis of gene conversion data

1986 ◽  
Vol 28 (5) ◽  
pp. 701-711 ◽  
Author(s):  
Bernard C. Lamb

Past attempts to obtain values for meiotic parameters relating to hybrid DNA formation and the correction of mismatched bases in hybrid DNA have not given unique solutions unless various simplifying assumptions were made. A method is given for identifying correct sets of solutions after calculating the frequency of hybrid DNA formation at a heterozygous site and using the fact that closely linked sites within a locus have very similar hybrid DNA formation frequencies. The method is illustrated with simulated data and Sordaria fimicola data; it can also show up incorrect assumptions in analysis. A method is suggested for assessing the importance of double-strand gaps in producing conversions.Key words: recombination, gene conversion, quantitative analysis.

1980 ◽  
Vol 35 (2) ◽  
pp. 179-194 ◽  
Author(s):  
J. R. S. Fincham ◽  
W. G. Hill ◽  
E. C. R. Reeve

SUMMARYCurrently favoured models postulate that gene conversion is due to the correction of mis-matches in heteroduplex DNA. If heteroduplex is formed reciprocally on both chromatids participating in recombination, the mis-matches due to a heterozygous site will be different on the two chromatids, and there will be four correction probabilities to be taken into account. It is shown that, given the frequencies of the five different kinds of aberrant ascus ratios, it is possible to calculate four alternative sets of values for the four correction probabilities and the total number of asci in which heteroduplex is formed. These four solutions reduce in effect to two when there are no other markers distinguishing the two chromatids. With the aid of flanking markers and the assumption that heteroduplex formation is chemically polarized, it is possible, in principle, to choose one best solution.The method has been applied to the five one-point crosses in Sordaria fimicola from which most data are available. The data from four different mutants crossed to wild type are compatible with a restricted model in which the correction frequencies, from mutant to wild and from wild to mutant, are the same on both chromatids. In the case of the fifth mutant the data are not consistent with this restricted model, and indicate different correction frequencies in the two chromatids.


Genetics ◽  
1985 ◽  
Vol 109 (3) ◽  
pp. 599-610
Author(s):  
Angelos Kalogeropoulos ◽  
Pierre Thuriaux

ABSTRACT A hybrid DNA (hDNA) model of recombination has been algebraically formulated, which allows the prediction of frequencies of postmeiotic segregation and conversion of a given allele and their probability of being associated with a crossing over. The model considered is essentially the "Aviemore model." In contrast to some other interpretations of recombination, it states that gene conversion can only result from the repair of heteroduplex hDNA, with postmeiotic segregation resulting from unrepaired heteroduplexes. The model also postulates that crossing over always occurs distally to the initiation site of the hDNA. Eleven types of conversion and postmeiotic segregation with or without associated crossover were considered. Their theoretical frequencies are given by 11 linear equations with ten variables, four describing heteroduplex repair, four giving the probability of hDNA formation and its topological properties and two giving the probability that crossing over occurs at the left or right of the converting allele.—Using the experimental data of Kitani and coworkers on conversion at the six best studied gray alleles of Sordaria fimicola, we found that the model considered fit the data at a P level above or very close (allele h4) to the 5% level of sampling error provided that the hDNA is partly asymmetric. The best fitting solutions are such that the hDNA has an equal probability of being formed on either chromatid or, alternatively, that both DNA strands have the same probability of acting as the invading strand during hDNA formation. The two mismatches corresponding to a given allele are repaired with different efficiencies. Optimal solutions are found if one allows for repair to be more efficient on the asymmetric hDNA than on the symmetric one. In the case of allele g1, our data imply that the direction of repair is nonrandom with respect to the strand on which it occurs.


1982 ◽  
Vol 40 (1) ◽  
pp. 1-18 ◽  
Author(s):  
Angelos Kalogeropoulos ◽  
Pierre Thuriaux

SUMMARYWe have extended previous algebraic analyses of aberrant segregation at the gray locus of Sordaria fimicola (Whitehouse, 1965; Emerson, 1966; Fincham, Hill & Reeve, 1980) to the more complex situation where aberrant segregations are detected in three factor crosses involving two flanking markers. This algebra has been applied to seven gray alleles which have been extensively characterized for their pattern of gene conversion and postmeiotic segregation by Kitani & Olive (1967). It is based on seven major types of aberrant segregation which can be distinguished in the presence of flanking markers spanning the converting site, and allows us to use up to six parameters to describe hDNA formation and mismatch repair. We present solutions which predict a spectrum of aberrant segregation fitting the experimental data at the P > 0·05 level for six of the seven alleles tested. They are consistent with the following properties of hDNA at the gray locus: (1) the single stranded DNA transferred during hDNA formation has always the same chemical polarity. (2) hDNA is mostly, if not entirely, symmetric, and its probability of formation is constant over the whole gene. (3) Disparity in aberrant segregation is mostly, if not entirely due to disparity in mismatch repair.


Genetics ◽  
2001 ◽  
Vol 159 (4) ◽  
pp. 1573-1593
Author(s):  
Muhammad Saleem ◽  
Bernard C Lamb ◽  
Eviatar Nevo

Abstract Recombination generates new combinations of existing genetic variation and therefore may be important in adaptation and evolution. We investigated whether there was natural genetic variation for recombination frequencies and whether any such variation was environment related and possibly adaptive. Crossing over and gene conversion frequencies often differed significantly in a consistent direction between wild strains of the fungus Sordaria fimicola isolated from a harsher or a milder microscale environment in “Evolution Canyon,” Israel. First- and second-generation descendants from selfing the original strains from the harsher, more variable, south-facing slope had higher frequencies of crossing over in locus-centromere intervals and of gene conversion than those from the lusher north-facing slopes. There were some significant differences between strains within slopes, but these were less marked than between slopes. Such inherited variation could provide a basis for natural selection for optimum recombination frequencies in each environment. There were no significant differences in meiotic hybrid DNA correction frequencies between strains from the different slopes. The conversion analysis was made using only conversions to wild type, because estimations of conversion to mutant were affected by a high frequency of spontaneous mutation. There was no polarized segregation of chromosomes at meiosis I or of chromatids at meiosis II.


Genetics ◽  
1988 ◽  
Vol 119 (2) ◽  
pp. 329-336
Author(s):  
T Langin ◽  
H Hamza ◽  
V Haedens ◽  
J L Rossignol

Abstract In the gene b2 of Ascobolus immersus, large heterologies increase the frequencies of reciprocal exchanges on their upstream border (corresponding to the high non-Mendelian segregation side). Tests were made to determine whether these reciprocal exchanges, instigated by large heterologies, resulted from the blockage of a Holliday junction bordering a hybrid DNA tract extending from the end of the gene to the heterology. Three types of experiments were performed to answer this question. In all cases, results did not correlate the presence of reciprocal exchanges instigated by large heterologies with the presence of adjacent hybrid DNA tracts. These reciprocal exchanges were rarely associated with postmeiotic segregation at upstream markers, they were not associated with gene conversion of a marker within the interval and their frequency was not decreased by decreasing the frequency of hybrid DNA formation in the gene. These results led to the proposal of the existence of a precursor to reciprocal exchange different from a single branch-migrating Holliday junction. This precursor migrates rightward and its migration is dependent on the DNA sequence homology. The existence of this precursor does not exclude that reciprocal exchanges resulting from the maturation of single Holliday junctions bordering adjacent hybrid DNA tracts could also occur.


2019 ◽  
Author(s):  
Michael Assaf ◽  
Shay Be’er ◽  
Elijah Roberts

Cells use genetic switches to shift between alternate stable gene expression states, e.g., to adapt to new environments or to follow a developmental pathway. Conceptually, these stable phenotypes can be considered as attractive states on an epigenetic landscape with phenotypic changes being transitions between states. Measuring these transitions is challenging because they are both very rare in the absence of appropriate signals and very fast. As such, it has proven difficult to experimentally map the epigenetic landscapes that are widely believed to underly developmental networks. Here, we introduce a new nonequilibrium perturbation method to help reconstruct a regulatory network’s epigenetic landscape. We derive the mathematical theory needed and then use the method on simulated data to reconstruct the landscapes. Our results show that with a relatively small number of perturbation experiments it is possible to recover an accurate representation of the true epigenetic landscape. We propose that our theory provides a general method by which epigenetic landscapes can be studied. Finally, our theory suggests that the total perturbation impulse required to induce a switch between metastable states is a fundamental quantity in developmental dynamics.


1970 ◽  
Vol 15 (1) ◽  
pp. 55-64 ◽  
Author(s):  
Andrzej Paszewski

SUMMARYSome features of gene conversion in fungi and their bearing on the hybrid DNA models are discussed. Available experimental data from tetrad analysis seem to give a more complex picture of polarity in intra-genic recombination and of the relations between conversion and post-meiotic segregation, and between conversion and crossing-over, than predicted by the models.A new hypothesis of the mechanism of gene conversion with special attention given to the aspect of asymmetry in this phenomenon is proposed as an alternative to the mechanism suggested by the DNA hybrid models.


2020 ◽  
pp. 105971231989648 ◽  
Author(s):  
David Windridge ◽  
Henrik Svensson ◽  
Serge Thill

We consider the benefits of dream mechanisms – that is, the ability to simulate new experiences based on past ones – in a machine learning context. Specifically, we are interested in learning for artificial agents that act in the world, and operationalize “dreaming” as a mechanism by which such an agent can use its own model of the learning environment to generate new hypotheses and training data. We first show that it is not necessarily a given that such a data-hallucination process is useful, since it can easily lead to a training set dominated by spurious imagined data until an ill-defined convergence point is reached. We then analyse a notably successful implementation of a machine learning-based dreaming mechanism by Ha and Schmidhuber (Ha, D., & Schmidhuber, J. (2018). World models. arXiv e-prints, arXiv:1803.10122). On that basis, we then develop a general framework by which an agent can generate simulated data to learn from in a manner that is beneficial to the agent. This, we argue, then forms a general method for an operationalized dream-like mechanism. We finish by demonstrating the general conditions under which such mechanisms can be useful in machine learning, wherein the implicit simulator inference and extrapolation involved in dreaming act without reinforcing inference error even when inference is incomplete.


1981 ◽  
Vol 35 (4) ◽  
pp. 421-428 ◽  
Author(s):  
Hugh E. Diem ◽  
Samuel Krimm

A general spectroscopic method for the analysis of binary mixtures which does not require external calibration has been developed. Spectra of the original mixture and of the mixture following some fractionation procedure are obtained. The method is based on the scaling factors required to null the components, one at a time, in successive absorbance subtractions of the two spectra. The accuracy is improved by a factor of approximately ten more than that of an earlier method. The effect of errors in the scaling factors on the analytical results is considered.


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