1. Announcements
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).
You should continue your X-linked crosses.
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.
Is there a serious problem taking the exam on Thurs. or Fri.???
Reminder that homework is due next Tues., Wed.
Quiz in lab next week; be prepared - pick up lab7 overview and read it.
Practice problems for Ch.8: 1,3,9,11; Ch.9: 4,8,10

2. 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

3. 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

4. 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

5. 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

6. 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

7. Maternal Effect: Snail Coiling
Pattern of offspring determined by genotype of mother, regardless of phenotype DD dd
dextral
sinistral
D egg, d sperm
D sperm, d egg Dd Dd
dextral
sinistral

8. Maternal Effect Genes in Drosophila Development
Discovered by Edward Lewis, Christiane Nusslein-Volhard 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: dorsal-ventral and anterior-posterior and control later zygotic genes.

9. Gene Map of the Y Chromosome
II. Sex Determination
Gene Map of the Y Chromosome

10. 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

11. XX/XO (Protenor) Mode
Female
Male
1:1 SEX RATIO

12. C. elegans Sex DeterminationXX XO
X/Autosome
Sets = 0.5
X/Autosome
Sets = 1

13. III. Normal Human Karyotypes
Female
Male

14. Klinefelter Syndrome (47, XXY)
Some male dev.
but no sperm, and
some female dev. too.
2 in 1000 male births

15. Turner Syndrome (45, X) Female dev. but no eggs.
1 in 3000 female births

16. 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

17. The Human Y Chromosome
NRY is non-recombining
region of Y

18. 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.

19. 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.

20. Genotypically Female Mice Transgenic for SRY are Phenotypically Male
XY male
XX male

21. IV. Dosage Compensation
Shouldn’t XX females produce twice the amount of X-linked 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.

22. Barr Bodies are Inactivated X Chromosomes in Females

23. 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

24. Lyon-Hypothesis: X-inactivation
A precursor cell to all coat color
cells
Random inactivation

25. Mosaicism Reveals the Random Inactivation of one X chromosome
Regions where
sweat glands
are absent.

26. Bilateral Gyandromorph (both Male and Female Genotypes)
Occurs from loss of one X (with wildtype alleles) at
1st mitotic division during development, oriented bilaterally.
Female (XX) half:
heterozygous for both
markers
Male (XO) half:
white,
miniature wing