Genetics Lecture 14, 10/1: Extranuclear inheritance, Sexual determination in Drosophila

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• TEST 2 MATERIAL
  
• • We are responsible for epistasis problems for the test (started it before exam 1)
• • Sex-linked traits
• • Nature vs. nurture. Multiple choice, short answer, essay
• • 3 to 4 problems comprising 50% of the credit. Mult. Choice is 20% and short ans. 30%.
• • Up through organelle heredity
• • Review is at NOON
• • Sex determination in Drosophila (unique system where they are more than male or female) (6:25)
• o 1916 Calvin Bridges
• • looking for the sex determination in fruit flies. He found that the mechanism was not Y dependent. He found that it was the ratio of X chromosome to autosomes determined the sex of the fly.
• o normal diploid female has 2 autosomes for every 2 x chromosomes. Ratio of 1.0
• o Triploid female extra copy of autosome and x chromosomes: total 3 autosomes to 3x chromosomes - ratio of 1.0
  

• o any arrangement with 1.0 would be a female
• o 3 x chromosomes for 2 autosomes gives ratio of 1.5. These are called metafemales: weak, infertile, low viability
• o Males have ratio of 0.5 two cases.
  
• • one x chromosome to two autosomes. Lack the Y chromosome leaving them sterile
• • One x chromosome one y chromosom --> fertile. Y chromosome determinse fertility, not maleness.
• o Metamales (14:20)
• • Ratio of 0.33. 1 x chromosome fore every 3 autosomes. They are weak and infertile
  
• o 2 classes of flies with ratios between 1 and .5 - Intersex flies
  
• • Intersex flies come about when there is: 3 X Chromosomes to 4 autosomes or 2 X chromosomes to 3 autosomes
• • Intersex flies: rudimentary gonads, sterile morphological, display both male and female (end of chap 7)
• • Chapter 9 (17:45) Extranuclear inheritance: anytime inheritance is not base on the DNA in the cells nucleus.
• o Ex. Organelle heredity – have DNA in the chloroplast and the mitochondria which influence phenotype. Always mother to offspring – egg contributes all of the cytoplasm → Organelles are in the cytoplasm.
• o Ex. Infectios Heredity – phenotype associated with a microorganism living in a cell.
• o Ex. Maternal effect – proteins in the egg which determine a particular phenotype in the offspring.
• o Only organelle heredity is DNA based
• • ORGANELLE HEREDITY (24:00)
• o 1908 Carl Correns worked with four O’clock plants. Either have white leaves, green, or veriegated leaves.
• o If the progeny came from a fertilization of an ovum from a plant with green leaves then the progeny had all green leaves.
• o Phenotype of the offspring was always the same as the phenotype of the parental plant that gave the ovum.
• o Phenotype is associated with the DNA of the chloroplast.
• Mitochondria can show the same pattern (28:10)
• o 1952 Mary and Hershey Mitchell studying Neurospora (bread mold) cross. Discovered a strain that they named Poky Strain (it grew slowly). Determined that the phenotype was associated with a mutation in the mitochondrial DNA. The mitochondria generates energy through respiration. Thus a mutation in the mitochondria would result in the slow growth phenotype.
• o Female poky x male WT THEN all progeny are were poky
• o female WT x male poky THEN all progeny were WT
• o The question: Do chloroplasts and mitochondira have their own DNA? → Yes
• o Cytoplasmic inheritance occurs through the cytoplasm of the egg. The sperm contributes NO cytoplasm.
• (35:30) DNA of the chloroplast
• o Uniform in size and shape and ranges from 100kB to 225kB (kb=kilobases)
• o Circular double stranded DNA with no associated proteins.
• o Genes found in chloroplasts DNA – genes for rRNA, tRNA ribosomal proteins and RNAPOL. This allows them to do their own transcription and translation independent o the cells individiual mechanisms for transcription and translation. They also have genes for photosynthesis.
• (38:40) Mitochondrial DNA
• o 16kB to 36kB
• o rRNA’s 22 different tRNA’s
• o genes whose products play a role in oxidative phosphorilation.
• o Ribosomes of mitochondria are quite different than the ribosomes of the rest of the cell.
• • Mitochondrial mutations associated with human diseases (41:30)
• o DNA in the mitochondria is particularly likely to be mutated
• o How do we determine that a human disease is mitochondrial in nature?
• • Inheritance pattern should be maternal and not mendelian.
• • Deficiency must result based on loss of energy for the cell
• • You must have a mutation in the gene in the mitochondrial DNA associated with the disease.
• o Myoclonic epilepsy and ragged red fiber disease (45:25): lack of coordination, deafness, dementia, epileptic seizures mutation in the mitochondrial gene for tRNA
• o Lebers hereditary Optic Neuropathy: Sudden bilateral blindness, avg. onset of 27
• o Kearns Sayre Syndrome: Hearing loss, loss of vision and heart condition. Normal childhood with an onset in early adulthood.

This will be material for TEST 3 ----------

• • INFECTIOS HEREDITY (50:25)
  
• o Eukaryote living in a symbiotic relationship with a microorganisms and leads to a phenotype.
• o EX. Paramecium Aurelia → a toxic substance which kills sensitive cells. Maintained by the Kappa gene.
• o Dominant K (kappa particle) allele to have the killer phenotype. You also need the microorganism which requires cytoplasmic exchange during paramecium mating.
• o Conjugation with cytoplasmic exchange or without.

Genetics Lecture 13, 9/29: Primary Sexual determination, Genetic diseases, dosage compensation

• • Human Embryonic, sexual differentiation (primary)
• o A relatively early process.
• o By the 5th week of gestation developmental gonads have appeared. Initially associated with the kidney.
• • Outer cortex
• Can become an ovary
• • Inner mendula
• Has the ability to develop into testes.
• o Ducts
• • Male → wolffian ducts
• • Female → mullarian ducts
• • The SRY has the testes determining factor. If this is present the development of the testes and male ducts is triggered. If it is NOT present (no Y chromosome) by week 12 we start to produce oogonia. Then we begin meiosis and by the end of the 25th week meiosis I is complete and all of the potential eggs are present in the female.
  
• • What can go wrong with sex chromosomes. (7:25)
• o Non-disjunction event: during meiosis, the sex chromosome pair fails to separate so you get unequal distribution of sex chromosomes in the gametes.
• o This leads to a number of syndromes associated with unusual sex chromosome arrangements.
• o Kleinfelter syndrome: males with two X chromosomes and a Y chromosome. These individuals are labeled 47 XXY where 47 is the number of chromosomes and XXY is the arrangement of the sex chromosomes.
• • Individuals can also have other arrangements: 48 XXXY, 48 IIYY, 49 XXXXY, 49 XXXYY
• • Generally the greater the number of X chromosomes the worse the syndrome.
• • Normal male ducts and normal genitals but the testes fail to form properly. The result is sterility.
• • Unusually long arms and legs, large hands and feet, undergo some female secondary sexual development including rounding of hips and some breast growth, below avg. intelligence.
• o Turner syndrome (14:40)
• • Also known as “45X”. Missing an X chromosome.
• • Female with normal female genitalia, normal female ducts, incomplete ovaries → sterility
• • Short in stature, skin flap on back of their necks
• o 47 XXX syndrome
• • some have it and are normal
• • others are underdeveloped sex characteristics, below avg. intelligence and sterile
• • ALSO: 48 XXXX and 49 XXXXX → traits become more pronounced.
• o 47 XYY syndrome (20:00)
• • Male, above average height. Below avg. intelligence, and socially awkward.
• • Theorized that this is more common in a prison population then the population at whole (controversial).
• • Ratio of males to females (not always one:one)
• o in theory, a heteromorphic (male) individual should make equal number of X and Y gamets.
• o Look at two ratios of males to females in the population
• o (25:25) Primary sex ratio: Ratio of male to female conceptions
• o Secondary Sex ratio: male to female births
• o Secondary sex ratios:
• • Caucasians: 1.06 (106 males to 100 females)
• o Question: Does the primary sex ratio 1.6 mean that more females die in the embryonic period than males?
• • observe miscarriages and abortion
• • primary sex ratio can be anywhere from 1.08 to 1.6 → this suggests that there are more male conceptions than female.
• o Primary sex ratio of 1 assumes:
• • Male will produce same number of x and y gamets
• • Each gamete type has the same viability in the reproductive tract
• • The egg is equally receptive to both gamete types.
• o (32:45) Current theory as to why “more males are born than females” is that the gamete bearing the Y chromosome is lighter and therefore faster than the gamete with an X chromosome.
• • Dosage compensation (35:30)
• o All of the autosomal chromosomes come in pairs.
• o Sex chromosomes – females have 2 X chromosomes males have 1 X chromosome. Twice as many copies of the X chromosome genes in females
• o Problematic – need to balance the amount of genes in all sexes.
• o Barr and Bertman – looking at DNA in interphase and they identified a dark staining body in the nucleus of females. They called it a Barr body. In females, one of the two X chromosomes is inactivated.
• o Barr body: inactivated X chromosome
• o How is the inactivation of one X chromosome determined?
• • Lyon hypothesis – the inactivation of the X chromosome is random. The same x chromosome is inactivated in every cell of an individual
• o Work to support lyon looks at:
• • Glucose – 6 – phosphate dehydrogenase (X chromosome gene)
• • Looked at a large number of individuals that were heterozygotes for the gene.
• • If the lyon hypothesis is correct then 50% of these will have the wildtype copy of the gene and 50% will have the mutant. (they did the test and it is correct – accepted as true)
• o How do you make a Barr Body and thus inactivate the X chromosome? (46:50)
• • A region on the X chromosome is responsible for this called the X inactivation center.
• • X inactivation center contains 4 genes: one of these genes when activated produces a functional RNA. It is Believed that this RNA covers the X chromosome that is inactivated. The coating is what prevents the X chromosome from functioning.

Genetics Lecture 12, 9/26: Sex determination and Sex Chromosomes

• • The chromosomes that determine sex are different.
• • Heteromorphic chromosome pair – a chromsome pair which is not homologous.
• o Ex. XY chromsome pair in human males
• • Multicellular organisms go through a two step sexual differentiation process.
• o Primary sexual differentiation. Embryonic, intial determination of male or female
• o Secondary sexual differentiation (puberty).
• • In general terms, organisms have one of two systems for sexes.
• o Unisexual organisms – the organism has one type of gonad, male or female
• o Bisexual – one organism with both gonads AND are fertile/functional
• • Life Cycles
• o Chlamydomonas – organism that rarely undergoes sexual reproduction. Spends the majority of the lifecycle as a haploid organism. Reproduce here through asexual reproduction. When the cells are stressed → nitrogen depletion. They will form isogametes, they will have two mating types, + and - . Mating is mating type dependent, plus with minus and vice versa. In turn you produce a diploid zygote. This diploid zygote will help protect the cell from the harsh conditions. When conditions improve the zygote undergoes meiosis and you produce vegetative cells (haploid).
• • C. Elegans (17ish)
• o Two sexes, hermaphrodites or males. Hermaphrodites have testes and ovaries and can make both functional gametes therefore they can self fertilize
• o 99% of worms are hermaphrodites 1% are males
• o hermaphrodites self fertilize – 99% herm. And 1% male
• o mate a male with a hermaphrodite you get 50% male and 50% herm.
• o In C. Elegans you have no Y chromosome so a hermaphrodite has two X chromosomes and the male has one X chromosome. SO when you self fertilize the hermaphrodite. 1% of males, due to non disjunction. Hermaphrodite produce a sperm or egg with no sex chromosomes.
• o Cross male and hermaphrodite with no sex chromosomes you get half herm. And half male.
• • (20ish)X and Y chromosomes were first linked to sex determination in the early 20th century. This was done in 1906 by Edmund Wilson.
• o Observed an insect called the protenor. Females with 12 autosomal chromomse and 2 X chromosomes. Produce gametes with 6 autosomes and 1 x chromosome.
• o Males have 12 autosomes and a sincle x chromosome. Produce two types of gametes. The first has 6 autosomes and x chromsome AND the other has 6 autosomes
• o In the protenor, maleness is defined by the lack of chromosome.
• • (24:30) – lygaeus mode of inheritance
• o females have 12 autromse and 2 X chromosomes
• o males have 12 autosome and Xand Y chromosome. Maleness is defined by the presence of a Y chromosome.
• o Typically the male of the species is the heteromorphic organism. There are some organisms where the female is heteromorphic.
• • Fish and reptiles – males are ZZ. Female is ZW
• • Y chromosome is responsible for maleness in humans (lygaeus mode of inheritance)
• o In 1920’s the Y chromosome was first visualized – small and heterochromatic.
• o Originally thought that humans had 48 chromosomes (we have 46). 44 are autosomes and an XX chromosomes and XY for males.
• • Y chromosome is genetically inert – very few important genes. HOWEVER – there are a number of important regions on the Y chromosomes.
• o PAR – pseudo autosomal region: regions that share homology with portions of the X chromosome. Allow the X and Y chromsome to bond to each orther during mitosis and meiosis. Represents 5% of the Y chromosome. The remaining 95% is called the NRY
• o NRY – non recombining region: this is genetically different from the X chromosome. 95% of the Y chromsome.
• o SRY – sex determining region of the Y chromosome: within it is a gene for the testes determining factor. This is a gene that is believed to be responsible for the development of testes.