Chromosomes: Vessels For The Genes

1. Chromosomes:Vessels For The Genes Timothy G. Standish, Ph. D.

2. Reasons Mendel’s Work Was Ignored: • There was no physical element in which Mendel’s inherited particles could be identified. • By the turn of the century, chromosomes had been discovered (physical particles) and biologists were better at math.

3. Chromosomes:The Physical Basis of Inheritance • 1866 Mendel published his work • 1875 Mitosis was first described • 1890s Meiosis was described • 1900 Mendel's work was rediscovered • 1902 Walter Sutton, Theodore Boveri and others noted parallels between behavior of chromosomes and alleles.

4. Chromosomal Theory of Inheritance • Genes have specific loci on chromosomes. • Chromosomes undergo segregation (meiosis) and independent assortment, • Thus alleles of genes are independently assorted.

5. Mother Father Telophase I e E Prophase I Crossing Over Replication e e E E e E e e E E n N N n n N n n N N e e E E N n N N n n Chromosomal Theory of Inheritance Telophase II

6. Eggs EN En eN en Sperm EN EENN EENn EeNN EeNn E N En EENn EEnn EeNn Eenn E n eN EeNN EeNn eeNN eeNn e e e E E N N N en EeNn Eenn n eeNn eenn n e n Independent Assortment As long as genes are on different chromosomes, they will assort independently

7. Mother Father Telophase I e e e E E E Prophase I Replication e e E E e E a a A A a a a A A A A A a a e E e E a a A A Two Genes On One Chromosome Telophase II As long as genes on the same chromosome are located a long distance apart, they will assort independently due to crossing over during Prophase I of meiosis

8. Thomas Hunt Morgan • First to associate a trait (gene) with a chromosome. • Worked with fruit flies (Drosophila melanogaster) • Why fruit flies? • Short generation time (≈ 2 weeks) • Survives and breeds well in the lab • Very large chromosomes in some cells • Many aspects of phenotype are genetically controlled.

9. Drosophila Mutations

10. More Drosophila Mutations Wild Type ++ ebony body ee white eyes ww

11. X Chromosome Human and Drosophila Genes Are Easy To Find • In humans and Drosophila, males are XY • Thus males are haploid for the X chromosome • Because of this, recessive genes on the X chromosome show up far more commonly in male than female phenotypes

12. X+ X+ Xw XwX+ XwX+ X P Y X+Y X+Y X X+ Xw F1 X+ X+ X+ XwX+ 1/4 1/4 1/2 Y X+Y XwY F2 Morgan’s Discovery Of An X-Linked Drosophila Gene A white-eyed male was discovered

13. The Key To Morgan’s Discovery • The key to Morgan’s discovery was the observation that all the white-eyed individuals in the F2 generation were males • Without this vital data on the association of white eyes with being male, the gene for white eyes could have been seen as a simple recessive trait on an autosome • This illustrates the importance of recording all the data possible and being alert to the possibility of interesting things being present in the data • “Fate favors the prepared mind” (Louis Pasteur)

14. Human X-linked Recessive Genes • Brown enamel - Tooth enamel appears brown rather than white • Hemophilia - Two types: • A - Classic hemophilia, deficiency of blood clotting factor VIII • B - Christmas disease, deficiency of blood clotting factor IX

15. X-linked Recessive GenesRelated to sight • Coloboma iridis - A fissure in the eye’s iris • Color Blindness - Two types: • Deutan - Decreased sensitivity to green light • Protan - Decreased sensitivity to red light • Congenital night blindness - Not due to a deficiency of vitimin A • Mocrophthalmia - Eyes fail to develop • Optic atrophy - Degeneration of the optic nerves

16. Victoria (1840-1901) Emperor Frederick III of Germany (1831-1888) Leopold Duke of Albany (1853-1884) Alice (1843-1878) King Edward VII of England (1841-1910) Beatrice (1857-1944) King Alfonso XIII of Spain (1841-1910) Alix (Alexandra) (1872-1918) Tsar Nicholas II of Russia (1868-1918) Irene (1866-1953) Victoria (1866-1953) Olga (1895-1918) Marie (1899-1918) Alexis (1904-1918) Tatiana (1897-1918) Anastasia (1901-1918) Royal Pedigree Edward Duke of Kent (1767-1820) Victoria Princess of Saxe-Coburg (1786-1861) Albert of Saxe-Coburg (1819-1861) Victoria Queen of England (1819-1910)

17. 1n Gamete + Interruption of meiosis 2n Gametes 3n Zygote Pro or Metaphase I Metaphase II Variation In Chromosome Number - Polyploidy • Polyploid individuals have more than two sets of chromosomes • Many important commercial plants are polyploid: • Roses • Navel oranges • Seedless watermelons • Polyploid individuals usually result from some sort of interruption during meiosis

18. + Zygote + Zygote Metaphase I Anaphase I Variation In Chromosome Number - Aneuploidy • Polyploid humans are unknown, but individuals with extra individual chromosomes are known. • Having extra chromosomes or lacking some chromosomes is called aneuploidy • Aneuploid individuals result from nondisjunction during meiosis

19. Aneuploidy In Humans • Most human aneuploids spontaneously abort • The most viable variations in chromosome number are those that deal with the sex chromosomes: • XO - Turner’s Syndrome - Phenotypically females • XXX…- “Super” females • XYY… - “Super” Males - On average tend to be larger and less intelligent • XXY - Klinefelter’s Syndrome - Phenotypically male • Of the non-sex chromosome aneuploidys, Down’s Syndrome, extra chromosome 21, tends to be the most viable • Down’s Syndrome is more common in children of mothers who gave birth after age 40

20. Gene Dosage • There seem to be elegant mechanisms for maintaining the correct dosage of genetic material in each cell • When aneuploidy causes a change in the relative dose of one chromosome, problems result

21. The Lyon Hypothesis • Having extra chromosomes causes problems (i.e., Downs Syndrome) • Men have only one X chromosome and they are normal (at least they think so) • Women have two X chomosomes and they are normal • Mary Lyon proposed that the extra dosage of X chromosome that women have is compensated for by turning off one of the X chromosomes. • This turned off chromosome can be observed as a “Barr Body” in metaphase female nuclei

22. Consequences of X Chromosome Dosage Compensation • Early during development, X chromosomes are randomly turned off in female cells • All daughter cells have the same X chromosome inactivated as their parental cell. • Thus, females are a mosaic of patches of cells some patches expressing the genes on the paternal X chromosome, other patches expressing the maternal X chromosome

23. XX XX XX XX XX XX Zygote XX XX XX XX Cell division XX Consequences of X Chromosome Dosage Compensation At some pont (probably later than the 4 cell stage) half the X chromosomes are turned off Daughter cells inherit the mother cell’s combination off and on X chromosomes Because of dosage compensation, females are thought to be a mosaic of patches of cells with each patch expressing the same X chromosome, but none expressing both chromosomes Different patches of cells inherit different act X chromosomes

24. Why Calico Cats Are Usually Female • Orange coat color is a sex-linked trait in cats (it is on the X chromosome) • A female cat heterozygous for orange, has skin patches expressing the orange X with the other X chromosome turned off. In other patches the opposite occurs.

25. The End