Chromosomal Theory of Inheritance: Understanding Genes, Segregation, and Mapping

1. Chromosomal Theory of Inheritance Chapter 15

2. The Theory • Genes are located on chromosomes • Chromosomes segregate and independently assort during meiosis

3. Evidence • Cytologists (study cells): • 1879 – Mitosis worked out • 1890 – Meiosis worked out • Geneticists (study genes): • 1860 – Mendel proposed laws of segregation & independent assortment • 1900 – Mendel’s work rediscovered

4. Sutton & Boveri • 1902 – identified parallels between Mendel’s factors and behavior of chromosomes • Work led to chromosomal theory of inheritance

5. Linkage & Chromosome maps • Linked genes are genes that are located on the same chromosome and DO NOT assort independently • We also know that chromosomes will also ‘cross-over’ during gamete formation • Based on the number of crossovers observed, we are able to determine the order of genes, and relative distance of genes from one another

6. Genetic recombination • Production of offspring with different traits than parents (also called recombinants)

7. Recombination of Unlinked Genes • In a testcross of YyRr x yyrr (yellow round x green wrinkled) • 25% yellow round • 25% green wrinkled • 25% yellow wrinkled • 25% green round • Happens due to random orientation of chromosomes during metaphase I (independent assortment occurs) Parental Types: 50% Recombinant Types: 50%

8. Recombination of Linked genes • The first thing we need to do is to calculate the percent of crossovers between genes • Example using Morgan’s flies: • b+ = grey vg+ = normal wings • b = black vg = vestigial wings • Grey, normal winged fly x Black vestigial winged fly • b+bvg+vg x bb vgvg • Cross produced 2300 flies

9. The numbers that we expected… • If genes are NOT linked, we would expect 50% to be normal (express the dominant trait) and 50% to express the recessive trait because independent assortment occurs • If genes ARE linked, we would expect 50% of offspring to be like the mother and 50% to be like the father because they will not sort independently

10. The numbers that we got…

11. Recombination frequency • When crossing over occurs, the genes are said to be recombinantgenes • To find the recombinant rate, we will add the two phenotypes where it was obvious that crossing over occurred and divide it by the total • Calculated by: # of recombinants ÷ Total # offspring • 206 + 185 = 391  391/2300 x 100% = 17% • These genes cross over 17% of the time

12. The Conclusion? • Genes are linked, but not totally • Crossing over in meiosis can cause genes to “unlink”

13. 17 Map Units b vg Genetic maps • We can translate recombination frequencies to “map units” • 1% = 1 map unit • The genes b and vg are 17 map units apart from one another

14. Making a Linkage Map • Let’s say we have 3 genes: • b = body color • cn = eye color • vg = wing size • We observed the following recombination frequencies: • What order should these genes be in?

15. 17 % 18.5 m.u. b b cn cn vg vg 9.5 % 9.5 m.u 9 % 9 m.u. • Due to the smaller amounts of crossovers between b-cn and cn-vg, and the large amounts between b-vg there are some discrepancies in the numbers. In cases like this, geneticists add the smaller numbers together when making a map.

16. Let’s try 4 Traits • The recombination frequencies are as follows: • Map this chromosome with the given information (given that these genes are linked)

17. The easiest thing to do is map the two furthest ones: • M and P were 11% apart • O seems to be equal between M and P (5.5%) • N is close to O (2.5%) But is it closer to P or M? • N-P= 8%; N-M= 3% • N is closer to M due to the lower percentage

18. M N O P 3 m.u. 2.5 m.u. 5.5 m.u. 11 m.u.

19. Sex Determination • Determined by presence of Y chromosome in humans • XX: female • XY: male • Other systems in birds, insects: • XO: insects • ZW: birds • Haplo-diploid: bees

20. SRY gene • Sex determination region • On Y chromosome • Triggers events that lead to testicular formation

21. Sex-linkage (or, X-linkage) • Some traits are only inherited because they are on the X chromosome • Typically recessive traits • Males inherit these more often • Why?

22. Sex linked disorders • Colorblindness • Hemophilia • Duchenne Muscular Dystrophy

23. Sample cross • Colorblindness • XC = normal vision • Xc = colorblind • XCXc x XCY • In any sex-linked cross: • Affected males Xc get from Mom • Affected females get one Xc from Mom and one from Dad • More males affected than females

24. X inactivation • Females are XX but only need one X • one X condenses and genes become silenced • Inactivation happens during embryonic development • Inactivation is random • Females are mosaics of 2 cell types • paternal X inactive • maternal X inactive

25. Chromosomal alterations • Mutations of chromosomes

26. Back to Mendel for a minute… • Looking at Mendel’s peas, it didn’t matter if the traits came from the maternal or paternal parent • Each trait would have the same bearing on the offspring • Scientists, within the past decade or so, have found some genes that are inherited differently depending on which parent passed it along

27. Genomic Imprinting • Variations in phenotype depending on whether the allele is passed on from the male or female parent • This differs from sex linkage due to the fact that most imprinted genes are found on autosomes

28. Imprinting • Occurs during gamete formation • These genes are expressed differently in eggs or sperm – the trait is ‘silenced’ in one gender • The developing embryo will only express the trait from one parent in all of its body cells • Effect is determined by which chromosome’s gene is expressed

29. Example – Igf2 • Insulin-like growth factor 2 (Igf2) is needed in mice for normal growth and development • In crosses between wild type and homozygous recessive dwarf mice, individuals produced heterozygous offspring • Offspring differed in phenotype depending on whether the gene was maternal or paternal

30. One More Genetic Exception… • Not all genes are found on nuclear chromosomes • Organelles such as mitochondria and chloroplasts have circular DNA molecules that carry genes • These are almost always passed on from the mother because the egg houses these organelles, while the sperm only carries chromosomes