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B C Lamb

Publications and source records attributed to B C Lamb.

At least 19 recordsLinked to original sources

Inherited differences in crossing over and gene conversion frequencies between wild strains of Sordaria fimicola from "Evolution Canyon".

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.

Biological Evolution↗

Gene conversion disparity in yeast: its extent, multiple origins, and effects on allele frequencies.

The extent of disparity in gene conversion direction in yeast (Saccharomyces cerevisiae) is important for recombination mechanisms and for effects of conversion on allele frequencies in populations. An analysis of published and unpublished data demonstrates that yeast frequently shows significant and extensive conversion disparity, contrary to many published statements. All types of mutation--base-substitutions, frameshifts and longer deletions and additions--can show significant 6:2/2:6 and/or 5:3/3:5 disparity. There was little correlation between the occurrence of 6:2/2:6 and 5:3/3:5 disparities; when both were significant, they were more often in opposite directions than in the same direction. Surprisingly, there was little correlation between a mutation's molecular nature and its disparity properties, which generally seem unpredictable. Disparity in yeast has multiple origins. From the equations discussed, all disparity types can be explained by one or more of: correction direction disparity, chromatid invasion disparity (including cases caused by different frequencies of double-strand breaks or gaps in nonsister homologous chromatids), strand invasion disparity, and different correction frequencies for the two types of mispair for a heterozygous mutation. Levels of overall disparity and of conversion frequency mean that conversion must often change allele frequencies in sexually reproducing yeast populations.

Alleles↗

Inherited and environmentally induced differences in mutation frequencies between wild strains of Sordaria fimicola from "Evolution Canyon".

We have studied whether there is natural genetic variation for mutation frequencies, and whether any such variation is environment-related. Mutation frequencies differed significantly between wild strains of the fungus Sordaria fimicola isolated from a harsher or a milder microscale environment in "Evolution Canyon," Israel. Strains from the harsher, drier, south-facing slope had higher frequencies of new spontaneous mutations and of accumulated mutations than strains from the milder, lusher, north-facing slope. Collective total mutation frequencies over many loci for ascospore pigmentation were 2.3, 3.5 and 4.4% for three strains from the south-facing slope, and 0.9, 1.1, 1.2, 1.3 and 1.3% for five strains from the north-facing slope. Some of this between-slope difference was inherited through two generations of selfing, with average spontaneous mutation frequencies of 1.9% for south-facing slope strains and 0.8% for north-facing slope strains. The remainder was caused by different frequencies of mutations arising in the original environments. There was also significant heritable genetic variation in mutation frequencies within slopes. Similar between-slope differences were found for ascospore germination-resistance to acriflavine, with much higher frequencies in strains from the south-facing slope. Such inherited variation provides a basis for natural selection for optimum mutation rates in each environment.

Acriflavine↗

Non-locus-specific polygenes giving responses to selection for gene conversion frequencies in Ascobolus immersus.

Selection for higher and lower meiotic conversion frequencies was investigated in the fungus Ascobolus immersus. Strains carrying the same known gene conversion control factors, which have major effects on conversion frequencies at their specific target locus, sometimes gave significant differences in conversion frequency. Selection for high or low conversion frequencies at the w1-78 site was practiced for five generations, giving significant responses in both directions. These responses were due to polygenes, or genes of minor effect, not to new conversion control factors of major effect. Crosses of selected strains to strains with other mutations showed that the genes' effects were not specific to w1-78, but could affect conversion frequencies of another mutation, w1-3C1, at that locus and of two other loci, w-BHj and w9, which are unlinked to w1 or to each other. The proportional changes in gene conversion frequency due to selection varied according to the locus and site involved and according to the conversion control factor alleles present. There were differences of > or = 277% in conversion frequency between "high" and "low" strains. Selection for conversion frequency had little effect on other features of conversion, such as the frequency of postmeiotic segregation or the relative frequencies of conversion to mutant or wild type.

Alleles↗

New equations and a method for finding nine parameter values for two alleles at one locus to study gene conversion using Ascobolus immersus.

A quantitative treatment is given for meiotic gene conversion with its parameters and equations for their interactions to determine allele segregation class frequencies from heterozygotes. The possible pairing of both pairs of nonsister chromatids in a bivalent at exactly the same point is included. Using sets of data from Ascobolus immersus, it is shown that values for all nine parameters for hybrid DNA models of recombination can be obtained using an iterative computer program. The accuracy of the values is estimated and the double-strand gap repair model is considered. The parameter values obtained invalidate most of the simplifications used in previous quantitative analyses of gene conversion data. They showed total bias in strand preference in asymmetric hybrid DNA formation and some bias in which type of chromatid is the invading one. There were slight differences in repair frequency between the two types of mispair and very large differences in the direction of repair. Conversion control factors had major effects on hybrid DNA formation and repair of mispairs.

Alleles↗

The effects of gene conversion control factors on conversion-induced changes in allele frequencies in populations and on linkage disequilibrium.

Conversion control factors (ccfs) are widespread. They control conversion properties at their target loci, affecting the conversion frequency and the amount and even the direction of gene conversion disparity. Three major types of ccf can be recognised. Experimental studies of the effects of ccfs have been combined with theoretical studies and modelling to examine the effects of ccfs on the evolutionary population genetics of alleles at the target locus. The ccf alleles present can greatly affect the rate and the direction of conversion-induced changes in target locus allele frequencies. Gene conversion can both cause and remedy linkage disequilibrium, with causation being related to polymorphism for ccfs. Disparity in conversion direction does not by itself necessarily cause linkage disequilibrium.

Alleles↗

Gene conversion disparity: factors influencing its direction and extent, with tests of assumptions and predictions in its evolutionary effects.

The evolutionarily important characteristics of gene conversion disparity extent and direction are surveyed in fungi. Temperature and background genotype can have small or large effects, sometimes even changing the direction of disparity. Disparity results from Sordaria and Ascobolus were very similar, with between-strain, between-data set and between-locus differences being larger than those between species or genera. In general, different loci in an organism show similar disparity properties when comparable types of mutation are considered, but may not do so in pooled results containing different proportions of different mutation types. Frameshifts typically have strong disparities, usually with negative signs for single base additions and positive signs for single base deletions. Base substitutions tend to have moderate disparities, favoring wild type more often than mutant in most data sets. Large deletions usually have significant disparity, either positive or negative. For comparable molecular types of mutation, spontaneous and induced mutations had roughly similar disparity properties.--Experimental tests and theoretical considerations generally failed to support a number of assumptions and predictions made in previous treatments of gene conversion in evolution. In general, a mutation's conversion properties depend much more on its molecular type in relation to wild type than on any evolved conversion advantages or disadvantages.

Alleles↗

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

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.

Chromatids↗

The effects of mispair and nonpair correction in hybrid DNA on base ratios (G + C content) and total amounts of DNA.

Base ratios and total DNA amounts can vary substantially between and within higher taxa and genera, and even within species. Gene conversion is one of several mechanisms that could cause such changes. For base substitutions, disparity in conversion direction is accompanied by an equivalent disparity in base ratio at the heterozygous site. Disparity in the direction of gene conversion at meiosis is common and can be extreme. For transitions (which give purine [R]/pyrimidine [Y] mispairs) and for transversions giving unlike R/R and Y/Y mispairs in hybrid DNA, this disparity could give slow but systematic changes in G + C percentage. For transversions giving like R/R and Y/Y mispairs, it could change AT/TA and CG/GC ratios. From the extent of correction direction disparity, one can deduce properties of repair enzymes, such as the ability (1) to excise preferentially the purine from one mispair and the pyrimidine from the other for two different R/Y mispairs from a single heterozygous site and (2) to excise one base preferentially from unlike R/R or Y/Y mispairs. Frame-shifts usually show strong disparity in conversion direction, with preferential cutting of the nonlooped or the looped-out strand of the nonpair in heterozygous h-DNA. The opposite directions of disparity for frame-shifts and their intragenic suppressors as Ascobolus suggest that repair enzymes have a strong, systematic bias as to which strand is cut. The conversion spectra of mutations induced with different mutagens suggest that the nonlooped strand is preferentially cut, so that base additions generally convert to mutant and deletions generally convert to wild-type forms. Especially in nonfunctional or noncoding DNA, this could cause a general increase in DNA amounts. Conversion disparity, selection, mutation, and other processes interact, affecting rates of change in base ratios and total DNA.

Animals↗

The properties of meiotic gene conversion important in its effects on evolution.

In order to determine how important gene conversion is as a force in populations, extensive surveys have been made to determine the limits, distributions and typical values of evolution-related conversion parameters from various fungi, Drosophila and maize. The conversion frequency, c, had an enormous range for different mutations within a species, with loci often having different means and limits for c. b, the frequency of a particular allelle in the products of meiotic tetrads or octads with aberrant segregation ratios, often showed values near the theoretical extremes; d, disparity in direction of conversion, was frequent and often extreme. b and d could only be studied in fungi, and their less extreme values in Saccharomyces than in Sordaria or Ascobolus are clearly related to the lack of frame-shift mutations in the yeast data. For different mutations at a locus, neither c nor b showed normal distributions; both gave dispersed distributions, sometimes multi-modal for b; c and b were not usually correlated. y, the force of meiotic gene conversion on allele frequencies, had a large range of positive and negative values, with different loci often having quite different limits and mean absolute values. For different mutations at a locus, y showed dispersed distributions, with little tendency to cluster around zero. The high proportion of non-zero y values in all fungi where this could be studied, with large departures from zero being most extreme in Ascobolus and Sordaria brevicollis, shows that gene conversion could often be an important force in changing allele frequencies in favour of mutant or wild-type in these organisms. Even in organisms with much lower c or absolute d values, conversion could still be important, depending on dominance, selection coefficients and mutation rates. Presumed frame-shifts tended to have more extreme disparity and hence higher absolute y values than did presumed base-substitutions, but with no consistent c differences. Induced mutations had similar or slightly higher absolute y values compared with spontaneous mutations.

Animals↗

The use of gene conversion to study synaptinemal complex structure and molecular details of chromatid pairing in meiosis.

Gene conversion can be used to study: the topography and pairing relationships of the four chromatids of a bivalent at the time of crossing over and hybrid DNA formation, the lengths of intimately paired segments and the frequency of intimate pairing at particular sites. Conversion ratios of different types, corresponding-site interference, co-conversion, and the range and distribution of conversion frequencies are discussed in relation to DNA and chromatid pairing, and synaptinemal complex organisation. Conversion data from Ascobolus immersus and other fungi are compared with electron microscope data from various organisms and with models of the synaptinemal complex.

Alleles↗

Randomness tests on the sequence of ascal segregation classes in Neurospora crassa.

Various statistical tests for randomness were made on the order of ascal classes in groups of asci from wild-type X asco crosses. There was no significant nonrandom clustering of asci of the same segregation class, nor a regular twinning of similar asci. Any apparent observed clustering of similar ascal classes is probably an artefact or due to chance. 2 x n X2 tests showed that frequencies of individual ascus classes from different perithecia were generally homogeneous, as were second division segregation frequencies. The tests described here for randomness in sequences of occurrences could be of general use in other areas of genetics.

Cell Division↗

Cryptic mutations: their predicted biochemical basis, frequencies and effects on gene conversion.

Cryptic mutations are undetected base changes in genetic DNA (or hereditary RNA). Some kinds of base change are normally undetected; others may or may not be detected, depending on experimental conditions, procedures and genotypes. Cryptic mutations could affect gene conversion results because when heterozygous they cause mismatched base pairs in hybrid DNA in the same way as known mutations, but the experimenter is unaware of them. Cryptic heterozygosity will usually be much more frequent in heterothallic than homothallic organisms. The effects of cryptic mutation heterozygosity on recombination and conversion of known mutations are predicted with reference to co-conversion, map expansion and polarity. Relevant evidence is considered.

Base Sequence↗