Chapter 5: Sex Determination and Sex Chromosomes

1. Chapter 5:Sex Determination and Sex Chromosomes Susan Chabot Honors Genetics 2014-2015

2. Chapter Concepts Sexual reproduction, which greatly enhances genetic variation, requires a mechanism for sexual differentiation. Usually, specific genes on a single chromosome determine male-ness or female-ness during development. A variety of mutations can lead to sexual dimorphism (differences). In humans, the presence of extra X or Y chromosomes above the normal diploid number can be tolerated but will lead to distinctive phenotypes.

3. Chapter Concepts There is NOT a 1-to-1 ration of males to females at conception; the ratio tends to favor males at conception. Female mammals inherit 2 X-chromosomes at conception; the additional information is inactivated in early development. Temperature of incubation for reptilian eggs will determine the sex of offspring.

4. Introduction • Homomorphic Chromosomes: • Heteromorphic Chromosomes: • It is the GENES on the chromosomes that determine sex of the organism. • MOST of these genes are on the sex chromosomes but some can be found on the autosomes.

5. Introduction • Homomorphic Chromosomes: XX pair in mammals. • Heteromorphic Chromosomes: XY pair in mammals. • It is the GENES on the chromosomes that determine the biological sex of the organism. • MOST of these genes are on the sex chromosomes but some can be found on the autosomes.

6. Vocabulary • Primary Sexual Differentiation: • Secondary Sexual Differentiation:

7. Vocabulary • Primary Sexual Differentiation: involves production and maturation of the gonads and gametes. • Secondary Sexual Differentiation: involves overall appearance of the organism; non-reproductive organs

8. Vocabulary • Unisexual/Dioecious/Gonohoric: • Bisexual/Monoecious/Hermaphroditic: • Intersex:

9. Vocabulary • Unisexual/Di-o-e-cious/Gono-choric: organism that contains only male or only female reproductive organs. • Bisexual/Mono-e-cious/Hermaphroditic: organism that contains both male and female reproductive organs. These organisms can produce both eggs and sperm. • Intersex: organisms of intermediate sexual condition; often sterile.

10. The Y Chromosome Determines Maleness in Humans • Human DIPLOID number is 46; HAPLOID number is 23. • Remember, chromosomes are only visible during MITOSIS and MEIOSIS. Visualization of chromosomes during cell division will allow for the construction of a karyotype, seen below.

11. Nondisjunction

12. Klinefelter Syndrome • 47, XXY • 1 in 600 male births! • Result of nondisjunction during Meiosis. • Tend to be tall, long arms, large hands and feet • Outward appearance of male • Undeveloped testes that fail to produce sperm. • Female secondary sex characteristics are not suppressed; rounded hips, slight breast enlargement. • Below average intelligence.

14. Turner Syndrome • 45, X • 1 in 2000 female births! • Result of nondisjunction during Meiosis • Short stature, skin flaps on back of neck, broad shield-like chest • Outward appearance of female • Undeveloped ovaries, may not produce eggs. • Normal intelligence

16. There are 3 levels to sexual development: • Chromosomal sex • Gonadal sex • Phenotypic sex

17. Levels of Sexual Development • Chromosomal sex: presence or absence of the Y chromosome. • Determined at fertilization • X or Y sperm that fertilizes egg. • Gonadal sex • Phenotypic sex

18. Chromosomal Variants • Rates for chromosomal changes = about 1 in 1000 births • Nondisjunction of sex chromosomes places <haploid or >haploid number of sex chromosomes into a sperm or egg cell. • Sex chromosomes are quite tolerant of variants. • Most common types involve 45 or 47 chromosomes • There are many other, rarer types, with 48 or even 49 chromosomes, such as 49,XXXXY. • Such conditions almost always lead to serious mental deficiencies. • The general rule: if the Y is present, the person is internally and externally male.

19. Nondisjunction

21. Levels of Sexual Development • Chromosomal sex • Gonadal sex (primary sex determination): do the gonads develop as testes or ovaries? • Depends on the presence or absence of the SRY gene, usually found on the Y chromosome • Phenotypic sex

22. Early Gonad Development • Gonadal ridges are produced by the 5th week of gestation. • The gonad is indifferent: neither male nor female. • Bipotential Gonads – can become ovary or testes • By week 6-7, differentiation has begun • The CORTEX will produce OVARIAN tissue and the medulla will disappear. • Mullerianducts = fallopian tubes, uterus, and vagina. • The MEDULLA will produce TESTICULAR tissue and the cortex will disappear. • Wolffian ducts = vas deferens and urethra.

23. SRY • How the Y chromosome determines sex. • The SRY is the primary determinant of sexual development. • If a developing embryo has a functional SRY gene in its cells, it will develop as a male. And, if there is no functional SRY, the embryo develops as female. • Although the SRY gene is usually on the Y chromosome, it occasionally gets transferred to the X. • this leads to 46,XX males • Sometimes the SRY gene is inactivated by mutation. • Leading to 46,XY females (Swyer syndrome) • it is also possible to have a partially inactive SRY gene, leading to ambiguous genitalia

24. Gene Mutations • Rates for gene mutations on Autosomes, each parent needs to contribute a mutated copy of the gene, usually 1 in 10,000 births. • Gene mutations can occur • On X or Y chromosome that impacts gonadal development • On Autosomes that produce enzymes responsible for converting sex chromosomes during fetal differentiation.

25. 5-alpha Reductase Deficiency (5-ARD) • Form of Intersex • Two copies of the gene must be defective. • 5-alpha reductase is an enzyme that converts testosterone into DHT. • DHT is responsible for the development of external male genitals • At birth • Undescended testes and male ducts (with no female ducts) • Genitalia appear somewhere between female and ambiguous • Often raised as girls • At puberty • Increase in testosterone is large enough that some DHT gets made • Develop a male appearance: the testes descend, the penis enlarges, facial hair appears, the voice deepens, muscles develop. • Large group in the Dominican Republic: ~ 1 in 90 men • Guevedoces - Raised as girls, they easily switch to the male role. • Other groups found in Malta, Jordan, Pakistan, New Guinea

26. Androgen Insensitivity • Incidence about 1 in 20,000 births • Formerly “testicular feminization”. • 46,XY with normal (undescended) testes. • During fetal development, testes secrete testosterone but cells lack receptors for it. • No receptor = no response to the hormone. • Result - male ducts are not present. Testes secrete MIS, which causes the female ducts to degenerate. • Typically external female genitals develop • At puberty, testes secrete excess testosterone and converts into a form of estrogen (estradiol). • Female secondary sexual characteristics develop. No menstruation, no ovaries, no uterus. Occasionally, the undescended testes can become cancerous, so they are often surgically removed after puberty is complete (so as to get normal female development).

27. Levels of Sexual Development • Chromosomal sex • Gonadal sex • Phenotypic sex (secondary sex determination): all internal and external structures develop depending on hormones secreted by the gonads. • Phenotypic sex = internal ducts, and external genitalia • Two important times: fetal development and puberty

28. Development of Phenotypic Sex • The cells of the newly formed testes start secreting testosterone. • Testosterone secretion peaks about week 16 (levels near adult males) then drops to about the same level as female fetuses. • The testes also secrete another hormone: Mullerian inhibiting substance (MIS) to destroy developing ovarian tissue. • During the last trimester of pregnancy, the testes descend into the scrotum. • The developing ovary secretes estrogen (important after birth) • Mom’s estrogen overwhelms the female fetus during pregnancy.

29. Childhood and Puberty • During childhood, sex hormone levels are very low in both sexes. • Surge of sex hormones in both sexes for a few weeks after birth. • Puberty begins when brain and hypothalamus produce the hormone gonadotropin releasing hormone. • Stimulates production of LH and FSH by the pituitary gland. • LH and FSH stimulate testes/ovaries to produce large amounts of testosterone and estrogen • In boys, some of the testosterone is converted to estrogen which causes a growth spurt. • The adrenal glands also secrete male sex hormones in both sexes starting in late childhood. • After puberty starts, the ovaries also produce androgens.