1. Sex Chromosomes Chapter 5 1

2. Outline Sex chromosomes Sex determination 2

3. 3 Role of Y Chromosome

4. Copyright © 2010 Pearson Education, Inc. Klinefelter and Turner Syndromes XXY XO

5. 47, XXX Syndrome Also called triploid-X or triplo-X Many times results in normal female Extra X can create reproductive issues, development, language, etc. 5 Note: Humans very intolerant of 3 rd copy of autosomes

6. 47, XYY Condition Males over 6 feet tall High correlation with behavioral problems (prison studies) 6

7. Copyright © 2010 Pearson Education, Inc. Human Y Chromosome 27 distinct protein-coding genes 12 are exclusively expressed in testes 95% length Protein coded this gene acts as “transcription” factor binding to DNA and causing fetus to develop testes

8. The Y-Chromosome Y has not lost any of the genes shared with chimps since Human line divergence 8-10 MYBP In fact only lost one gene since Great Apes split from Monkeys

9. Inheritance of Y-Chromosome Y-Adam lived 50,000 to 150,000 years ago

10. (46, X ai Y)- AIS: Androgen Insensitivity Syndrome X-linked recessive (Xq11-12) ( genetically male, phenotypically female ) Androgen hormone interaction with the Androgen receptor early in fetal tissue development regulates proper development of genitals. 10 46 X AI X ai and X ai X ai no effects

11. Copyright © 2010 Pearson Education, Inc. Barr bodies Dosage compensation X-chromosome inactivation 15% of X-chromosome genes escape inactivation

12. Copyright © 2010 Pearson Education, Inc. Karotypes with extra X Chromosomes have extra Barr Bodies Norm male Norm female Klinefelter Syndrome Turner’s Syndrome

13. Copyright © 2010 Pearson Education, Inc. Lyon Hypothesis X-chromosome inactivation occurs randomly in somatic cells in early embryonic development Can lead to mosaic expression as in female calico cats Calico / tabby

14. 14 Some cat fur color genes are X-linked When an X-chromosome is Inactivated, all its subsequent daughter cells are similarly inactivated

15. Copyright © 2010 Pearson Education, Inc. Mechanism of X-inactivation Epigenetic memory – daugher cells of silenced cells are also silenced XIC on inactivated X chromosome encodes the Xist gene RNA transcribed from Xist gene silences X-chromosome genes q arm Active Inactive HYPERMETHLATEDHYPERMETHLATED

16. Copyright © 2010 Pearson Education, Inc. Mechanism of X-inactivation Xist is RNA gene (no protein coded) and is part of “XIC” X-Inactivation Center along with 2 other RNA genes and two protein-coding genes q arm Active Inactive HYPERMETHLATEDHYPERMETHLATED

17. Copyright © 2010 Pearson Education, Inc. Mechanism of X-inactivation q arm Active Inactive Becomes Barr Body; Barr Body Duplicates Later in S-phase of Cell cycle than active X

18. 18 Random X M X P in females Except germ cell production Days, weeks and months Post conception The Inner Cell Mass will consist of cells that are Pre-XCI, XCI and some never XCI

19. 19 When a cell Inactivates One Of Its Two X-Chromosomes, All Subsequent Daughter Cells Will Carry the Same X M vs X P Inactivation 43 of the 233 X-linked genes escape inactivation. Some of these are in the “PAR” region, others do not have Y-equivalents, many on the short “p” arm.

20. 20 100 million years of mammalian evolution PROTOXPROTOX PROTOXPROTOX Without X-Inactivation X-Chromosome Transcript of males would be half that of females

21. 21 100 million years of mammalian evolution PROTOXPROTOX PROTOXPROTOX Without X-Inactivation X-Chromosome Transrcipt of males would be half that of females Gradual Incremental X-Inactivation

22. 22 Concept: The evolutionary pressure for the Y chromosome dictated need to suppress one of the two X chromosomes. Why? I like the hypothesis which starts with "the mammalian X and Y chromosomes evolved from a pair of autosomes (widely accepted)." As the developing or evolving Y acquired its sex-determining region (authors below describe the evolutionary pressures) it slowly lost the genes on the "proto-X chromosome." With each evolutionary step toward a more specialized Y chromosome a bit more of proto-X's genes were lost. The evolutionary response to maintain gene dosage was up-regulation of "un-partnered" genes on the X chromosome. Over more than 100 million years of mammalian evolution the Y chromosome became highly specialized in infinitely small subtle evolutionary steps. To compensate for the increasing up-regulation, one of the X-chromosomes in females (XX) needed to be silenced. Hence, X-inactivation. It too probably evolved in small evolutionary steps. https://www.musc.edu/mbes-ljg/Courses/Biology%20of%20Reproduction/ https://www.musc.edu/mbes-ljg/Courses/Biology%20of%20Reproduction/ Paper%20pdfs/Waters%20Wallis%20Graves%202007.pdf