The Nature of Sex

1. The Nature of Sex Ricki Lewis Klug and Cummings

2. Platypus Sex Chromosome • Platypus - Echidna • Earliest type of mammal duck like bill, web feet,fur, and mammary glands • The platypus, long thought a strange creature, just got stranger • Researchers discovered that it has 10 sex chromosomes, • Some of them linked to mammals and some to birds.

3. Evolution of the Sex Chromosomes - Marsupials • http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=53113&tools=bot • http://www.newscientist.com/article.ns?id=dn6568

4. The Nature of Sex – The sex chromosomes in humans

5. The Evolution of Y • The X and Y chromosomes diverged around 300 million years ago when some reptile, the distant ancestor of all mammals, developed a so-called 'male gene' - simply possessing this gene caused the organism to be male. • The chromosome with this gene became the Y chromosome, and a similar chromosome without it became the X chromosome. • So initially, X and Y chromosomes were nearly identical. Over time, genes which were beneficial for males and harmful to (or had no effect on) females either moved to or developed on the Y chromosome.

6. Recombination between X and Y • Recombination between the X and Y chromosomes proved harmful - it resulted in males without necessary genes formerly found on the X chromosome • Females were found with unnecessary or even harmful genes previously only found on the Y chromosome. • As a result, genes beneficial to males assembled near the sex-determining genes in order to make this less probable. Eventually, the Y chromosome changed in such a way as to inhibit the areas around the sex determining genes from recombining at all with the X chromosome.

7. The evolution of the Y • With time, larger and larger areas became unable to recombine with the X chromosome. • This caused its own problems: without recombination, the removal of harmful mutations from chromosomes becomes increasingly difficult. • These harmful mutations continued to damage Y-unique genes until several finally stopped functioning and became genetic junk; this was eventually removed from the Y chromosome.

8. More about the Y chromosome • As a result of this process 95% of the human Y chromosome is unable to recombine, the chromosome itself contains only 83 working genes • Compare this to close to 1000 working genes on the X chromosome. • In some animals, Y degradation is even more severe. For example, the kangaroo Y chromosome contains only the SRY gene

9. The Y chromosome • The Y chromosome has a p and q arm • The SRY gene bestows the male identity • The pseudoautosomal region is on the q arm

10. Y chromosome • Short and long arm • There are 63 pseudoautosomal genes that cross over with the X chromosome • Bulk of the Y chromosome is termed the male-specific region or MSY • The MSY lies between the two pseudoautosomal regions

11. MSY and Pseudoautosomal genes • The MSY lies between the two pseudoautosomal regions and it consista of three classes of DNA sequences • About 10 to 15 % of the MSY consists of X transposed sequences that are 99 percent identical to counterparts on the X chromosome

12. MSY and the other • The remainder of the MSY contains palindrome ridden regions called amplicons • Most of the MSY genes are vital to fertility

13. Y chromosome • Although 95% of the Y chromosome lies between the pseudoautosomal regions, fewer than 80 genes have been found here. • Over half of this region is genetically-barren heterochromatin. Of the 80-odd genes found in the euchromatin, some encode proteins • The others encode proteins that appear to function only in the testes. A key player in this latter group is SRY.

14. SRY • The SRY encodes a transcription factor • It sends signals to the indifferent gonads early in the development of the embryo

15. Genes on the Y chromosome • AMELY (amelogenin,Y-chromosomal) • ANT3Y (adenine nucleotide translocator-3 on the Y) • ASMTY (which stands for acetylserotonin methyltransferase) • AZF1 (azoospermia factor 1) • AZF2 (azoospermia factor 2) • BPY2 (basic protein on the Y chromosome) • CSF2RY (granulocyte-macrophage colony-stimulating factor receptor, alpha subunit on the Y chromosome) • DAZ (deleted in azoospermia) • IL3RAY (interleukin-3 receptor) • PRKY (protein kinase, Y-linked) • RBM1 (RNA binding motif protein, Y chromosome, family 1, member A1) • RBM2 (RNA binding motif protein 2) • SRY (sex-determining region) • TDF (testis determining factor) • TSPY (testis-specific protein) • UTY (ubiquitously transcribed TPR gene on Y chromosome) • ZFY (zinc finger protein)

16. Human Chromosome LaunchPad • http://www.ornl.gov/sci/techresources/Human_Genome/launchpad/chromY.shtml

17. Tracing the history of the Y • indels - insertions into or deletions of the DNA at particular locations on the chromosome. One insertion particularly useful in population studies is the YAP, which stands for "Y chromosome alu polymorphism." Alu is a sequence of approximately 300 letters (base pairs) which has inserted itself into a particular region of the DNA. There have been some half a million alu insertions in human DNA; YAP is one of the more recent. • snips - are "single nucleotide polymorphisms" in which a particular nucleotide (an A, for example) is changed (perhaps into a G). Stable indels and snips are relatively rare and, in the case of the latter, so infrequent that it is reasonable to assume they have occurred at any particular position in the genome only once in the course of human evolution. Snips and stable alus have been termed "unique event polymorphisms" (UEPs).

18. Tracing the history of the Y • microsatellites are short sequences of nucleotides (such as GATA) repeated over and over again a variable number of times in tandem. The specific number of repeats in a particular variant (or allele) usually remains unchanged from generation to generation but changes do sometimes occur and the number of repeats may increase or decrease.

19. Tracing the Y • The fourth polymorphism category is minisatellites, extensively studied by Mark Jobling at the University of Leicester. Unlike microsatellites, in which the repeated sequences are short (often no more than 3 or 4 nucleotides), • In minisatellites they are normally 10-60 base pairs long and the number of repeats often extends to several dozen. Changes during the copying process take place more frequently in minisatellites than in microsatellites and the mechanisms may be different in the two cases.

20. The Y chromosome and the European Men • http://www.raceandhistory.com/Science/europeanmen.htm

21. The X chromosome

22. Mammalian comparison

23. Unraveling the X

24. X Chromosome – related genes • Alport syndrome • Androgen insensitivity syndrome • Becker's muscular dystrophy • Centronuclear myopathy • Charcot-Marie-Tooth disease • Coffin-Lowry syndrome • Duchenne • Fabry disease • Fragile X syndrome • Glucose-6-phosphate dehydrogenase deficiency • Hemophilia • Incontinentia pigmenti • Lesch-Nyhan syndrome • Menkes disease • Myotubular myopathy • Nonsyndromic deafness and X-linked nonsyndromic deafness • Ornithine transcarbamylase deficiency • Rett syndrome • Spinal and bulbar muscular atrophy • X-linked severe combined immunodeficiency (SCID) • X-linked agammaglobulinemia (XLA) • X-linked sideroblastic anemia

25. X and Y chromosomes • Genes on the X chromosome are referred to as X linked • Genes on the Y chromosome are referred to as Y linked

26. X inactivation • There are two X chromosome in females • One is inactivated early in embryological development • The inactivation is random so that only one chromosome is active in each cell • Females are mosaics of the X chromosomes

27. Barr Body • The Barr Body is the remnant of the X chromosome

28. Calico Cats

29. Sex Limited • Genes that are only expressed in one sex • Antlers in male deer • Milk production in female cows

30. Sex influenced • Baldness in males • Traits that are expressed with one copy in males and two copies in females( with hormonal influence)

31. Genomic imprinting • The phenomenon of genomic imprinting is the differential modification of the maternal and paternal genetic contributions to the zygote, resulting in the differential expression of parental alleles during development and in the adult. • A disturbance in genomic imprinting in humans has been shown to play a role in several birth defects, genetic diseases and cancers. • In humans, the most convincing demonstration of an imprinted region is at chromosome 15q11-q13 with a deficiency of the maternal region resulting in the Angelman syndrome (AS) and a deficiency of the paternal region resulting in the Prader-Willi syndrome (PWS).

32. Genomic imprinting

33. Prader Willi • short stature • small hands and feet • hypotonia and poor muscle development • excess fat, especially in the central portion of the body • narrow forehead • almond shaped eyes with thin, down-turned lips • light skin and hair relative to other family members • lack of complete sexual development in adolescence

34. Angelman Syndrome

35. Angelman Syndrome • Severe developmental delay (100%) • Minimal use of words or nonverbal; receptive skills higher than expressive skills (100%) • Movement or balance disorder including, wide based gait with feet turned outward, tremulous movement of limbs, and uncoordinated movements (100%) • Behavioral uniqueness such as frequent laughter or smiling, happy demeanor, easily excitable often with hand flapping movements, hypermotoric behavior (can be seen in infants as ceaseless activity), and a short attention span (100%) • Microcephaly by age 2 (>80%) • Seizures of any type by age 3 years (>80%) • Abnormal EEG (>80%) • Strabismus (20-80%) • Tongue thrusting and suck and swallow disorders (20-80%) • Feeding problems in infancy (20-80%) • Hypopigmented skin and eyes (20-80%) • Hyperactive tendon reflexes (20-80%) • Uplifted arms when walking (20-80%) • Prominent mandible (20-80%) • Wide mouth/wide spaced teeth (20-80%)