Hartl, Jones - Genetics. Principlers and analysis - 1998 (522927), страница 54
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The genetic constitution of the maternally derived X chromosomes in the normal-eyed offspringwas also inconsistent with such an explanation: The male offspring had cut wings and the females were ct/+heterozygotes. That is, all of the rare nonlozenge progeny had an X chromosome with the constitutionwhich could be accounted for by recombination between the two lozenge alleles. Proof of this conclusion camefrom the detection of the reciprocal recombinant chromosomein five male progeny that had a lozenge phenotype distinctly different from the phenotype resulting from thepresence of either a lzBS or lzg allele alone. The exceptional males also had vermilion eyes, as expected fromreciprocal recombination.
The observation of intragenic recombination indicated that genes have a fine structureand that the multiplicity of allelic forms of some genes might be due to mutations at different sites in the gene. Aswe have seen in Chapter 1, these sites are the nucleotide constituents that make up DNA.Page 1614.8—A Closer Look at ComplementationThe discovery of intragenic recombination emphasized the question "What is a gene?" A gene cannot be definedsolely on the basis of a mutant phenotype.
On the one hand, mutations in different genes can yield similarphenotypes. On the other hand, multiple alleles of the same gene can have quite different phenotypes, dependingon the residual function of the mutation and the time- and tissue-specificity of its expression.An alternative definition of a gene is based on recombination: Two mutations with similar phenotypes are alleles ofthe same gene if they fail to recombine. The discovery of recombination between alleles of lozenge and betweenalleles of other genes in Drosophila showed that this definition of a gene is unacceptable. Allelic mutations canrecombine.
The theoretical problem posed by recombination between alleles is indicated by the term pseudoallelesused to designate alleles that recombined. However, we now know that there is nothing "pseudo" aboutpseudoalleles. They are perfectly legitimate alleles that are far enough apart along the DNA to allow the detectionof recombination.The experimental resolution of the problem of the definition of a gene was the complementation test discussed inChapter 2.
The test is the same sort of test one would use to find out whether holes in each member of a pair ofsocks were in the same place. Put both socks on the same foot. If the holes are in the same place, bare skin showsthrough where the holes overlap. If the holes are in different places, each hole is covered by the fabric present inthe other sock. In the complementation test, two recessive alleles are regarded as alleles of the same gene if, whenthey are present together in the same organism, they fail to complement each other and so yield a mutantphenotype, the "bare skin."When a set of recessive mutations is tested in all pairwise combinations, the complementation test enables them tobe separated into groups called complementation groups (Chapter 2).
For example, in a genetic analysis of flowercolor in peas, a geneticist may isolate many independent recessive mutations, each of which causes the flowers tobe white instead of purple. To group the mutations into complementation groups, strains that are homozygous fordifferent mutations are crossed in all possible pairs. If the progeny of a cross has white flowers, then the mutationsin the parents are said to fail to complement. These mutations are classified as belonging to the samecomplementation group, which means that they are alleles of the same gene. On the other hand, if the progeny of across between two mutant strains has purple flowers, then the mutations in the parents are said to complement. Themutations are assigned to different complementation groups, which means that they are alleles of different genes.The molecular basis of complementation is illustrated in Figure 4.30.
Figure 4.30A depicts the situation when twomutations, m1 and m2, each resulting in white flowers, are different mutations of the same gene. (The site of eachmutation is indicated by a cross.) In a genotype in which m1 and m2 are in the trans, or repulsion, configuration, m1codes for a protein with one type of defect and m2 codes for a protein with a different type of defect, but both typesof protein are nonfunctional. Hence alleles in the same gene yield a mutant phenotype (white flowers), becauseneither mutation is able to support the production of a wildtype form of the protein.When the mutations are alleles of different genes, the situation is as depicted in Figure 4.30B.
Because themutations are in different genes, the homozygous m1 genotype is also homozygous for the wildtype allele of thegene mutated in m2; likewise, the homozygous m2 genotype is also homozygous for the wildtype allele of the genemutated in m1. Hence the same cross that yields the genotype m1/m2 in the case of allelic mutations (Figure 4.30A),in the case of different genes yields the genotype m1+/+ m2, where the plus signs represent the wildtype alleles ofthe genes not mutated in m1 and m2. In this case, the mutations do complement each other and yield an organismwith a wildtype phenotype (purple flowers).
With respect to the protein rendered defective by m1, there is afunctional form encoded by the wildtype allele brought in from the m2m2 parent.Page 162Figure 4.30The basis for interpretation of a complementation test used to determine whether two mutations are alleles of the same gene (A) oralleles of different genes (B).With respect to the protein rendered defective by m2, there is again a functional form encoded by the wildtype allelebrought in from the m1m1 parent.
Because a functional form of both proteins is produced, the result is a normalphenotype, or complementation.Complementation and recombination must not be confused. Complementation is inferred from the phenotype of thetrans- heterozygote having a mutation in each of two different genes (Figure 4.30B). Recombination is inferredfrom genetic analysis of the progeny of heterozygous genotypes.Chapter SummaryNonallelic genes located in the same chromosome tend to remain together in meiosis rather than to undergoindependent assortment. This phenomenon is called linkage. The indication of linkage is a significant deviationfrom the 1 : 1 : 1 : 1 ratio of phenotypes in the progeny of a cross of the form Aa Bb × aa bb. When alleles of twolinked genes segregate, more than 50 percent of the gametes produced have parental combinations of thesegregating alleles, and fewer than 50 percent have nonparental (recombinant) combinations of the alleles.
Therecombination of linked genes results from crossing-over, a process in which nonsister chromatids of thehomologous chromosomes exchange corresponding segments in the first meiotic prophase. At the molecular level,the Holliday model explains recombination as a result of a single-strand break in each of two homologous DNAmolecules, interchange of pairing partners between the broken strands, and repair of the gaps, followed by strandmigration and a second breakage and reunion to connect the originally unbroken DNA strands.
This model,although not correct in all its details, is nevertheless the basis on which more accurate and complex models ofrecombination have been developed.The frequency of recombination between different genes can be used to determine the relative order and locationsof the genes in chromosomes. This type of analysis is called genetic mapping. Distance between adjacent genes insuch aPage 163map (a genetic or linkage map) is defined to be proportional to the frequency of recombination between them; theunit of map distance (the map unit or centimorgan) is defined as 1 percent recombination.
One map unitcorresponds to a physical length of the chromosome in which a crossover event takes place, on the average, once inevery 50 meiotic divisions. For short distances, map units are additive. (For example, for three genes with order a bc, if the map distances a to b and b to c are 2 and 3 map units, respectively, then the map distance a to c is 2 + 3 = 5map units.) The recombination frequency underestimates actual genetic distance if the region between the genesbeing considered is too great. This discrepancy results from multiple crossover events, which yield either norecombinants or the same number produced by a single event.
For example, two crossovers in the region betweentwo genes may yield no recombinants, and three crossover events may yield recombinants of the same type as thatfrom a single crossover.When many genes are mapped in a particular species, they form linkage groups equal in number to the haploidchromosome number of the species. The maximum frequency of recombination between any two genes in a crossis 50 percent; this happens when the genes are in nonhomologous chromosomes and assort independently or whenthe genes are sufficiently far apart in the same chromosome that at least one crossover is formed between them inevery meiosis. The map distance between two genes may be considerably greater than 50 centimorgans because themap distance is equal to half of the average number of crossovers per chromosome times 100. A mapping functionis the mathematical relation between the genetic map distance across an interval and the observed percentrecombination in the interval.In many organisms, including model experimental organisms, agricultural animals and plants, and human beings,the genetic map includes hundreds or thousands of genetic markers distributed more or less uniformly throughoutthe euchromatin.
Some of the most useful genetic markers are changes in base sequence present in wildtypeorganisms that are not associated with any phenotypic abnormalities. Prominent among these are nucleotidesubstitutions that create or destroy a particular cleavage site recognized by a restriction endonuclease. Suchmutations can be detected because different chromosomes yield restriction fragments that differ in size accordingto the positions of the cleavage sites.
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