Lecture 5 Chapter 4: Sex Determination and Sex-Linked Characteristics
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1 Lecture 5 Chapter 4: Sex Determination and Sex-Linked Characteristics Sex determination may be controlled: chromosomally genetically (allelic) environmentally Chromosomal determination Haplodiploidy (bees, wasps) Allelic determination Some plants Environmental determination Behavioral (some fish) Temperature (many reptiles) Position Sex determination in the common slipper Limpet Chromosomal: Heterogametic Male Female 1. XO system: grasshoppers X0 XX 2. XY system: humans XY XX 3. ZW system: birds ZZ ZW Top: male First and bottom: female 1
2 Sex Determination in Drosophila Determined by ratio of X chromosomes to number of haploid sets of autosomes Sex Determination in Humans XX: female XY: male Sex Chromsomes Haploid Sets Complement of Autosomes X:A Ratio Sexual Phenotype XX AA 1.0 Female XY AA 0.5 Male XO AA 0.5 Male XXY AA 1.0 Female XXX AA 1.5 Metafemale XX AAA 0.67 Intersex X:A 1.0 or greater: Female X:A between 1.0 and 0.5: Intersex X:A 0.5 or less: male 2
3 XO: female Turner s Syndrome 1/3000 female births XXY Male Klinefelter Syndrome: 1/1000 male births Less commonly: XXXY or XXXXY or XXYY Role of Sex Chromosomes in Humans (and most but not all mammals) Identification of the Male-determining Gene in Humans 1. XX males and XY females: sex reversal 2. Some shown to have a piece of the Y on an X. 1. Absence of the Y chromosome gives a female phenotype. 2. Essential genes on the X for both sexes. 3. Male determining gene (Testis Determining Factor) is located on the Y.. 4. Genes affecting fertility are located on the X, Y, and autosomes. 5. The proper number of X chromosomes is usually needed for fertility. 3. Some shown to have a deletion in the Y. 4. Mapping of these regions, first with cytogenetics, then with molecular techniques allowed ID of region responsible. 5. ZFX gene is probably the Testis Determining Factor! 6. New XX male patients found with a tiny piece of the Y and no TDF. 7. Critical gene on the Y: the SRY gene (Sex reversal on the Y) 3
4 Morgan explained sex-linked inheritance Read: androgen-insensitivity syndrome Sex-linked characteristics: determined by genes located on the sex chromosomes X-linked characteristics Y-linked characteristics When in doubt, use Punnett squares! He found a fly with white eyes a male. 4
5 Question: Are white eyes in fruit flies inherited as an autosomal recessive trait? Found answer by doing reciprocal crosses. First experiment Second experiment Consistent with Mendel s results But 3/1237 were white-eyed males Autosomal recessive trait in F2 s: ¼of males ¼ of females Bridges: rare flies with wrong eye color were due to failure of the X s to separate in anaphase I: nondisjunction of the X chromosome. Morgan proposed that eye color is on the X chromosome 5
6 X-Linked Inheritance in Humans: Color Blindness Blue pigment: chromosome 7 Red and green pigments: two loci near each other on the X Color blind allele: c Wild type allele: + X c X c X + X c Dosage Compensation Different numbers of X s in males versus females Different numbers of genes for each gene on the X Problem with different amounts of gene products Animals overcome this via dosage compensation. Barr body Fruit flies: double the activity of genes on the X in males Placental mammals: inactivate one of the X chromosomes in females Mary Lyon proposed: Barr body is an inactive X chromosome and results in dosage compensation. Choice of which X is inactivated is random = Lyon Hypothesis 6
7 Dosage Compensation in humans: the number of Barr bodies is always one less than the number of X chromosomes. Dosage Compensation Random X inactivation early in development. Inactivation gradually spreads across one X starting at the X-inactivation center. Region localized, partially by natural X:autosome translocations, then by moving candidate genes into other cells. Xist gene identified: makes a large RNA that is not translated! On X that will be inactivated: Xist RNA is transcribed and coats that X chromosome X inactivation. Some genes on the inactive X escape inactivation. Possible source of problems in XO females, XXY males? Both X chrom s. active in newly fertilized eggs Females develop to a many cell stage. Then get random inactivation of one of the X s. mosaicism in expression of X chrom. genes in females Example: anhidrotic ectodermal dysplasia. Phenotype includes absence of sweat glands. XaXA XaY Xa(XA) or (Xa)XA Y-linked traits Passed along exclusively by males. Can be used to follow the male lineage. Y-linked markers showed that Thomas Jefferson had sons via one of his slaves. Calico cats: nearly always female Sex-influenced traits not encoded on the Y but influenced by the sex of individual. 7
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