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Biology, Genetics, Linkage, Mapping


  • Chapter 7. Linkage, Crossing Over, & Chromosome Mapping in Eukaryotes

    1. Linkage, Recombination, and Crossing over2. Chromosome Mapping3. Cytogenetic Mapping*

  • Chiasmata in the late prophase of the first meiotic division. These cross-shaped figures are the result of exchanges between paired chromosomes.*

  • The World's First Chromosome Map

    chromosome organization emerged from a combination of genetic and cytological studies.

    T. H. Morgan laid the foundation for these studies when he demonstrated that the gene for white eyes in Drosophila was located on the X chromosome.

    The map was a straight line, and each gene was situated at a particular point, or locus, on it

    Locus: A fixed position on a chromosome that is occupied by a given gene or one of its alleles.*

  • One night in 1911 Sturtevant, undergraduate working in Morgan's laboratory put aside his algebra homework in order to evaluate some experimental data.

    Before the sun rose the next day, he had constructed the world's first chromosome map.


  • No microscope was powerful enough to see genes, nor was any measuring device accurate enough to obtain the distances between them.

    In fact, Sturtevant did not use any sophisticated instruments in his work.

    Instead, he relied completely on the analysis of data from experimental crosses with Drosophila. *

  • 1. Linkage, Recombination, and Crossing Over

    Sturtevant based his mapping procedure on the principle that genes on the same chromosome should be inherited together.

    Because such genes are physically attached to the same structure, they should travel as a unit through meiosis. This phenomenon is called linkage.

    Linkage: A relationship among genes in the same chromosome. Such genes tend to be inherited together. *

  • The early geneticists also knew that linkage was not absolute.

    Their experimental data demonstrated that genes on the same chromosome could be separated as they went through meiosis and that new combinations of genes could be formed.

    However, this phenomenon, called recombination, was difficult to explain by simple genetic theory.


  • One hypothesis was that during meiosis, when homologous chromosomes paired, a physical exchange of material separated and recombined genes.

    cytological observation A crossover point was called a chiasma (plural, chiasmata), from the Greek word meaning cross. *

  • Exceptions to the Mendelian principle of independent assortment Bateson and Punettsweet peastwo traits, flower color and pollen lengthRed flower, long pollen grain are dominant.9:3:3:1 ???


  • 24.3:1.1:1:7.1=803*

  • The chi-square value is enormousmuch greater than 7.8, which is the critical value for a chi-square distribution with three degrees of freedom

    Consequently, we must reject the hypothesis that the genes for flower color and pollen grain length have assorted independently *

  • Some nonparental progeny do appear, although at low frequency. Because these progeny indicate that the alleles of the two genes were recombined in the F1, they are called recombinants. *

  • Frequency of recombination as a measure of linkage intensity

    We can use the frequency of recombination to measure the intensity of linkage between genes. Genes that are tightly linked seldom recombine, whereas genes that are loosely linked recombine often.


  • Each phenotype is highlighted by a different color in the Punnett square. These phenotypes do not appear in a 9:3:3:1 ratio because the genes for flower color and pollen length are located on the same chromosome. *

  • Frequency of recombination as a measure of linkage intensity

    The most direct way of estimating the frequency of recombination is to use a testcross, in which the individual to be analyzed genetically is crossed to a homozygote carrying the recessive alleles. *

  • AA BB individual is crossed to an aa bb individual.

    From this cross, the Aa Bb offspring are then testcrossed to the double recessive parent.

    Because the A and B genes assort independently, the F2 will consist of two classes (Aa Bb and aa bb) that are phenotypically like the parents in the original cross, and two classes (Aa bb and aa Bb) that are phenotypically recombinant.

    Furthermore, each F2 class will occur with a frequency of 25 percent. *

  • *

  • For any two genes, the frequency of recombinant gametes never exceeds 50 percent.

    This upper limit is reached when genes are very far apart, perhaps at opposite ends of a chromosome.

    It is also reached when genes are on different chromosomes; 50 percent recombination is, in fact, what is meant when it is said that the genes assort independently.


  • Crosses involving linked genes are usually diagrammed to show the linkage phasethe way in which the alleles are arranged in heterozygous individuals linkage phase : coupling linkage phase repulsion linkage phase*

  • Crossing Over as the Physical Basis of Recombination

    Recombinant gametes are produced as a result of crossing over between homologous chromosomes.

    The exchange event occurs during the prophase of the first meiotic division, when duplicated chromosomes have paired.

    Although four homologous chromatids are present, forming what is called a tetrad, only two chromatids cross over at any one point. *

  • Crossing over as the physical basis of recombination*

  • The evidence for crossing over between two chromatids within a tetrad comes from the study of certain fungi in the class Ascomycetes, Saccharomyces cerevisiae.

    One important finding from studies with S. cerevisiae is that crossing over occurs after homologous chromosomes have duplicated.

    An ascus may contain two recombinant and two nonrecombinant ascospores, each of which has a different genotype.

    This observation can only be explained if crossing over occurs after chromosome duplication. If it occurred before duplication, an ascus could never contain more than two kinds of ascospores.*

  • A second finding is that only two chromatids are involved in an exchange at any one point.

    However, the other two chromatids may cross over at a different point.

    Thus, there is a possibility for multiple exchanges in a tetrad of chromatids *

  • *

  • *

  • Evidence That Crossing Over Causes Recombination

    In 1931 Harriet Creighton and Barbara McClintock obtained evidence that genetic recombination was associated with a material exchange between chromosomes.

    Creighton and McClintock studied homologous chromosomes in maize that were morphologically distinguishable.

    The goal was to determine whether physical exchange between these homologues was correlated with recombination between some of the genes they carried.*

  • Harriet Creighton and Barbara McClintock:

    maize two forms of chromosome 9

    one was normal, and the other had cytological aberrations at each enda heterochromatic knob at one end and a piece of a different chromosome at the other


  • Evidence that crossing over causes recombination

    Kernel color ( C, colored ; c, colorless ) Kernel texture (Wx, starchy ; wx, waxy )*

  • Evidence that crossing over causes recombination


  • xChiasmata and the Time of Crossing Over

    The cytological evidence for crossing over can be seen during late prophase of the first meiotic division when the chiasmata become clearly visible. *

  • Diplonema of male meiosisin the grasshopper Chorthippus parallelusxAs we might expect, large chromosomes typically have more chiasmata than small chromosomes.

    Thus, the number of chiasmata is roughly proportional to chromosome length.

    When the heat shocks were administered late in prophase, there was little effect, but when they were given earlier, the recombination frequency was changed. *

  • xAlthough almost all the DNA is synthesized during the interphase that precedes the onset of meiosis, a small amount is made during the first meiotic prophase.

    This limited DNA synthesis has been interpreted as part of a process to repair broken chromatids, which, as we have discussed, is thought to be associated with crossing over. *

  • x*

  • 2. Chromosome Mapping

    1) Crossing over as a measure of genetic distance

    Sturtevant's fundamental insight was to estimate the distance between points on a chromosome by counting the number of crossovers between them. Points that are far apart should have more crossovers between them than points that are close together.

    In a statistical sense. The distance between two points on the genetic map of a chromosome is the average number of crossovers between them. *

  • *

  • we cannot see each of the exchange points on the chromosomes coming out of meiosis.

    Instead, we infer their existence by observing the recombination of the alleles that flank them. *

  • nonrecombinants recombinants (0) x 0.82 + (1) x 0.18 = 0.18 - map unit a centiMorgan ( cM , M )

    2) Recombination mapping with a two-point testcross*

  • 3) Recombination mapping with a three-point testcross Determination of the gene order Three possible gene orders: (i)sceccv (ii)ecsccv (iii)eccvsc

    cv ec sc *

  • *

  • Calculation of the distances between genes*

  • Calculation of the distances between genes*

  • We can also obtain th

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