1. GENERAL GENETICS Ayesha M. Khan Spring 2013

2. Linkage  Genes on the same chromosome are like passengers on a charter bus: they travel together and ultimately arrive at the same destination.  Linkage happens when genes don’t assort independently.  Genes on the same chromosome are linked.  Genes linked on the same chromosome segregate together.  Crossing Over involves reciprocal exchange of chromosome segments between homologs; increases genetic variation (recombination). 2

3. Notation for Crosses with Linkage  Genotypes + arrangement of genes on the chromosome  For linked genes, it is necessary to write out the specific alleles as they are arranged on each of the homologous chromosomes.  Each line represents one of the two homologous chromosomes.  Example: AABB x aabb 3 -simplified by drawing only a single line, with the understanding that genes located on the same side of the line lie on the same chromosome:

4. 4 Idealized Mendelian ratios (independent assortment): (Dihybrid cross) RrYy x RrYy  9:3:3:1 (Test cross) RrYy x rryy  1:1:1:1 These idealized ratios occur when alleles of the two genes don’t “care” about one another (don’t segregate together) “Linkage” is one of the exceptions to the idealized ratio

5. Complete Linkage Compared with Independent Assortment Complete linkage: genes located on the same chromosome and do not exhibit detectable crossing over A testcross reveals the effects of linkage: -A heterozygous individual is test-crossed with a homozygous recessive individual (AaBb X aabb), -Whatever alleles are present in the gametes contributed by the heterozygous parent will be expressed in the phenotype of the offspring, because the homozygous parent could not contribute dominant alleles that might mask them. Consequently, traits that appear in the progeny reveal which alleles were transmitted by the heterozygous parent. 5

6. 6 MmDd x mmdd If not closely linked, alleles will assort independently ▫MmDd individual can form 4 different types of gametes ▫50% recombinant offspring/50% non- recombinant offspring Testcross for linkage:

7. 7 MD/md x md/md If closely linked, 2 alleles will always travel together ▫all offspring are non- recombinant Testcross for linkage:

8. 296 19 27 85 Observed number 15.6 1.0 1.4 4.5 Ratio 9 3 3 1 240 80 27 Expected Under indep. assort Purple flowers, long pollen (PPLL) Purple flowers, long pollen Purple flowers, round pollen Red flowers, long pollen Red flowers, round pollen F2F2 P0P0 F1F1 Purple flowers, long pollen (PpLl ) Self-fertilization x Red flowers, round pollen (ppll ) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Brooker Figure 7.1 Much greater proportion of the parental types than recombinant types When genes are linked, the two traits do NOT segregate independently

9. 9 Linkage with Recombination Linkage without Recombination Complete Linkage Compared with Independent Assortment (contd)

10. Linkage without crossing over creates only parental (noncrossover) gametes. Linkage with crossing over creates parental gametes and recombinant (crossover) gametes. In summary, a testcross in which one of the plants is heterozygous for two completely linked genes yields two types of progeny, each type displaying one of the original combinations of traits present in the P generation. Independent assortment, in contrast, produces two types of recombinant progeny and two types of nonrecombinant progeny in equal proportions. 10

11. Crossing Over with Linked Genes 11 meiosis  For closely linked genes, crossing over does not take place in every meiosis. meioses  In meioses in which there is no crossing over, only nonrecombinant gametes are produced. meioses  In meioses in which there is a single crossover, half the gametes are recombinants and half are nonrecombinants (because a single crossover only affects two of the four chromatids) meioses  The total percentage of recombinant gametes is always half the percentage of meioses in which crossing over takes place.

12. Recombination Frequency 12 Recombinant Frequency = (number of recombinant progeny/total number of progeny) x 100% Smaller the recombination frequency = more closely linked

13. Coupling and Repulsion Two possible arrangements on the chromosomes of the heterozygous fly: This arrangement, in which wild-type alleles are found on one chromosome and mutant alleles are found on the other chromosome, is referred to as coupling, or the cis configuration. This arrangement, in which each chromosome contains one wild-type and one mutant allele, is called the repulsion or trans configuration. 13 Example: Inheritance of two linked genes in the Australian blowfly, Lucilia cuprina. One locus determines the color of the thorax: purple thorax (p) is recessive to the normal green thorax (p+). A second locus determines the color of the puparium: a black puparium (b) is recessive to the normal brown puparium (b+).

14. Coupling and Repulsion (contd) Test-cross a fly that is heterozygous at both loci with a fly that is homozygous recessive at both: When the alleles are in the coupling configuration, the most numerous progeny types are those with green thorax and brown puparium and those with purple thorax and black puparium; but when the alleles of the heterozygous parent are in repulsion, the most numerous progeny types are those with green thorax and black puparium and those with purple thorax and brown puparium. 14

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16. Connecting Linkage, independent assortment and crossing over No linkage: ▫exhibit independent assortment; ▫An individual heterozygous at two loci (AaBb) produces four types of gametes in equal proportions: two types of nonrecombinants and two types of recombinants (AB, ab, Ab, and aB) Complete linkage: ▫genes do not recombine; ▫do not assort into new combinations; ▫An individual heterozygous at two loci (AaBb) produces only the nonrecombinant gametes (AB or ab) Incomplete linkage: ▫intermediate between independent assortment and complete linkage; ▫genes are physically linked on the same chromosome, which prevents independent assortment; ▫However, occasional crossovers break up the linkage and allow them to recombine; ▫An individual heterozygous at two loci (AaBb) produces four types of gametes—two types of recombinants and two types of nonrecombinants—but the nonrecombinants are produced more frequently than the recombinants because crossing over does not take place in every meiosis. 16

17. Recombination mechanisms Interchromosomal recombination ▫Between genes on different chromosomes ▫Produces 50% recombinant/50% non-recombinant gametes Intrachromosomal recombination, ▫Between genes on same chromosome ▫Usually produces recombinant gametes less than 50%  Unless very far apart on the same chromosome 17

18. Morgan’s Interpretation Recombination was caused by linear arrangement of genes and crossing over. two genes that lie far apart are more likely to undergo a crossover than are two genes that lie close together. Frequency of recombination was determined by distance between genes: – y and w recombination rate = 1.3% –w an m recombination rate = 37.2% –Therefore y and w were closer together on the chromosome, while w an m are farther apart.

19. Map distances Linked genes with greater physical distance between them are more likely to have a recombination event  1% recombination = map unit (mu) or 1 cM (centimorgan) e.g. 12% recombination = 12 mu or 12 cM Recombination frequency < 50%  “linked”. Recombination frequencies > 50% = “unlinked” Recombination frequency = 0% recombination  “completely linked” Typical chromosome: 200 mu Typical gene =.01 mu or 60,000 nucleotides

20. Genetic mapping Chromosome maps calculated by using recombination frequencies are called genetic maps. ▫Relative position of different genes based on recombination rates/frequencies. Does NOT state actual chromosome, or position (locus) Distance measured in map units or centimorgans (cM) ▫1 m.u. (or cM) = 1% recombination ▫one morgan equals 100 m.u.

21. 21 Genetic distances measured with recombination rates are approximately additive:

22. Physical mapping Chromosome maps based on physical distances along the chromosome (often expressed in terms of numbers of base pairs) are called physical maps ▫Locates gene to a specific chromosome/region of chromosome