Transcript Document

Announcements
1. We have decided to halt our efforts with the yw crosses, due to
uncooperative yw females, frustration, and lack of motivation (we KNOW
the expected results). There will be no assignment due for this lab
activity. You are responsible for understanding the expected results and
how to calculate recombination frequencies and map distance (ie. flylab
6).
2. You should continue your X-linked crosses.
3. Vote on when to review for exam 2 (10/17, 10/18) - Mon. evening or in
class Wednesday. If we review in class Wed, then class meets Fri. If we
review Mon., then class meets Wed.
4. Is there a serious problem taking the exam on Thurs. or Fri.???
5. Reminder that homework is due next Tues., Wed.
6. Quiz in lab next week; be prepared - pick up lab7 overview and read it.
7. Practice problems for Ch.8: 1,3,9,11; Ch.9: 4,8,10
Review of Last Lecture
1.Quick review of conjugation: F-, F+, Hfr
2. Transformation: a different process of recombination,
can be used to map genes
3. Bacteriophages are viruses that use bacteria as hosts;
they can mediate bacterial DNA transfer - transduction
4. Extrachromosomal inheritance: Phenotype of maternal
parent is solely responsible for phenotype of offspring example of maternal inheritance of chloroplasts
Outline of Lecture 16
I. Two more examples of extrachromosomal inheritance:
mitochondria and “maternal effect”
II. Modes of sex determination
III. Humans and sex determination
IV. Dosage compensation
I. Mitochondrial Heredity
• About 30,000 genes on 23 human chromosomes (3.3
billion base pairs/haploid cell)
• Mitochondrial Genome contains 37 genes:
– 13 code for some of the proteins involved in
oxidative respiration
– 22 tRNA genes
– 2 rRNA genes
– some proteins involved in mt protein synthesis
– 16,569 base pairs, circular
Human Mitochondrial Diseases
• Are maternally inherited: only offspring of affected
mothers are affected
• Show deficiency in mitochondrial function
• Are caused by a mutation in a mitochondrial gene
• Example: myoclonic epilepsy and ragged red fiber
disease (MERRF)
– Deafness, dementia, seizures
– Point Mutation in a mitochondrial tRNA
Other Human Mitochondrial
Diseases
• Leber’s Hereditary Optic Neuropathy (LHON)
– Sudden bilateral blindness
– Point mutation in small subunit of NADH
dehydrogenase
• Kearns-Sayre Syndrome (KSS)
– Symptoms in eyes, muscles, heart, brain
– Deletion mutation in mtDNA
Maternal Effect: Snail Coiling
• Pattern of offspring determined by genotype of mother,
regardless of phenotype
dextral
DD
dd
D egg, d sperm
dextral
Dd
sinistral
D sperm, d egg
Dd
sinistral
Maternal Effect Genes in Drosophila
Development
• Discovered by Edward Lewis, Christiane NussleinVolhard and Eric Weischaus (Nobel Prize in
Physiology or Medicine, 1995)
• Gene products deposited in egg by cells of mother’s
ovary.
• These genes set up the first embryonic axes: dorsalventral and anterior-posterior and control later zygotic
genes.
II. Sex Determination
Gene Map
of the
Y Chromosome
Modes of Sex Determination
• XX/XO (Protenor)
– absence of second X chromosome determines
maleness
– as in Caenorhabditis elegans
• XX/XY (Lygaeus)
– presence of Y chromosome determines maleness
– in mammals
• sometimes females are heterogametic sex
Female
Male
XX/XO
(Protenor)
Mode
1:1 SEX RATIO
C. elegans Sex Determination
XX
X/Autosome
Sets = 1
XO
X/Autosome
Sets = 0.5
III. Normal Human Karyotypes
Female
Male
Klinefelter Syndrome (47, XXY)
Some male dev.
but no sperm, and
some female dev. too.
2 in 1000 male births
Turner Syndrome (45, X)
Female dev.
but no eggs.
1 in 3000 female births
The Odyssey of the Germ Cells
• Primordial Germ Cells are set aside early in
embryonic development
• PMG’s migrate to embryonic kidney ridges:
– If cells are XY, medulla develops into testes under
direction of male hormones around week 7
– If cells lack a Y, cortex develops into ovary, also
under active hormonal control
– Active gene expression required in either case
• Duct differentiation:
– If XY, Wolffian ducts > epididymis and vas
deferens
– If no Y, Mullerian ducts > oviduct
The Human Y Chromosome
NRY is non-recombining
region of Y
Testis-Determining Factor
• Was the object of an intense search.
• SRY gene on the Y chromosome was identified as
the gene that codes for TDF:
– SRY is translocated to X in rare XX males
– SRY is absent from Y in rare XY females
• The “home run” experiment by Koopman et al. used
transgenic mice.
The Transgenic Sry Experiment:
How It Was Done
• Reference: Nature 351:117 (1991)
• Nuclei of fertilized XX eggs were injected with Sry
gene, then the eggs were transplanted to surrogate
mothers.
• Sry gene then randomly incorporated into a
chromosome and was inherited in subsequent cell
divisions.
• Animals karyotyped after development to adult.
Genotypically Female Mice Transgenic for
SRY are Phenotypically Male
XY male
XX male
IV. Dosage Compensation
• Shouldn’t XX females produce twice the amount of Xlinked gene products as XY males?
• No, because XX females “compensate” by
inactivating one of their X chromosomes to make a
single “dosage” of X-linked genes.
Barr Bodies are Inactivated X
Chromosomes in Females
The Lyon Hypothesis of X Inactivation
• Proposed by Mary Lyon and Liane Russell (1961)
• Inactivation of X chromosome occurs randomly in
somatic cells during embryogenesis
• Progeny of cells all have same inactivated X
chromosome as original, creating mosaic individual
Lyon-Hypothesis: X-inactivation
A precursor cell to all coat color
cells
Random inactivation
Mosaicism Reveals the Random
Inactivation of one X chromosome
Regions where
sweat glands
are absent.
Bilateral Gyandromorph (both Male and
Female Genotypes)
Occurs from loss of one X (with wildtype alleles) at
1st mitotic division during development, oriented bilaterally.
Male (XO) half:
white,
miniature wing
Female (XX) half:
heterozygous for both
markers