Download Chapter 7: Outline Sexual Differentiation Heterogametic Sex

Chapter 7: Outline
• Sexual Differentiation
Heterogametic
• Human Male/Female
– Y C-some
– Dosage compensation
• Drosophila Male/Female
– X to autosome Ratio
– Dosage compensation
• Reptile Male/Female determination
– Environmental factors (Temperature)
Sexual Differentiation
• Sexually reproducing organisms depend upon fertilization of gametes
formed during meiosis
• Fertilization relies on some form of sexual differentiation between
individuals
• Genetic basis is often related to different C-some composition between the
sexes
– The Heterogametic sex either lacks one C-some or contains a unique C-some
Heterogametic Sex Determination
• Protenor (insect): XX/X0
– Random distribution of the X c-some into only half of the male gametes
– Females=XX (Homogametic)
– Males=X0 (Heterogametic)
• Lygaeus (insect): XX/XY
– Random distribution of Y c-some into male gametes
– Females=XX (Homogametic)
– Males=XY (Heterogametic)
• Males not always Heterogametic
– ZZ/ZW Mode, where female=ZW
Human Sex C-somes
• Humans have a diploid (2n) number of 46
– 22 homologous pairs of Autosomes
– 1 homologous pair of sex chromosomes
– Typical Males=XY and Females=XX
• X and Y C-somes
– Very different in Appearance and DNA composition
Heteromorphic
– Pair during meiosis/mitosis
Possible Interpretations
• Y C-some determines maleness in humans
– Have the Y then you will express male phenotype
• Y C-some does not play a role in sexual development
– Presence of two XX determines femaleness
– Lack of the second X C-some determines maleness
Human Sexual C-some Abnormalities
• Klinefelter Syndrome (47,XXY)
– Male genitalia and internal ducts
– Testes are underdeveloped and fail to produce sperm
• Turner Syndrome (45, X)
– Female genitalia and internal ducts
– Underdeveloped ovaries
• XXX Syndrome
– Female genitalia and internal ducts
– Normal to sterility
• XYY Condition
– Male genitalia and internal ducts
– Above average height
Correlation of Y with Maleness
• Appears to be a high degree of correlation between the Y C-some and the
development of maleness
• Molecular biologists also observed that in the absence of Y C-some, no
male development occurs
• What is so special about the Y C-some?
Y C-some Structure
• Shares very little homology with the X C-some
– Less than 10% is shared between X and Y C-somes
– Regions termed PARs (Pseudoautosomal regions)
– A few allelic X genes
• Rest is termed NRY (Nonrecombining region of Y)
– Much of this is genetically blank (no genes) termed Heterochromatin
– Some Y C-some specific genes have been discovered
Observations
• Some individuals who appeared to express Turner Syndrome (X0) were
shown to have mutated Y C-some
– Lost (missing) p arm of Y
• Studies examining XX Males and XY Females established that
translocations or mutations of Y p arm were present
• By correlating the extent of Y alterations to phenotypes the interval
bearing the male-determining factor (called TDF, testis-determining
factor), was narrowed down to 35 kb on the p arm of Y
SRY Gene
• Sex-determining region of Y (SRY) was identified as the TDF
– Testis-specific expression
– XX (Males) and XY (Females) are often missing this SRY region
– Highly conserved in mammals
– Inserting this gene in XX mice (transgenic) and observed male development
• Not the only gene on the Y C-some involved in Male development
Genetic Dosage Problem
• X C-somes are very similar to autosomes both in appearance and genetic
content
• Females contain 2x X genes
– Do females producing 2 times X-linked genes than males?
– How are males viable with only half the genetic X material?
– Do males X c-some produce 2x the amount as female X?
• How do humans compensate for this genetic dosage problem?
Dosage Compensation
• Females shut down one of their X C-some in somatic cells in a process
called Lyonization
– X-inactivation occurs in the first few days after fertilization (a few hundred cells)
– In each cell, one of the X C-some becomes highly condensed forming a Barr body
– Inactivation is stably transmitted to all subsequent progeny cells
• Random average half maternal and half paternal
• Can produce mosaics: patches of tissue expressing the allele in one X and alternating patch
expressing other allele
Drosophila Sex Determination
• Males and females of drosophila have the same sex C-some composition
as humans
– Male=XY and Female=XX
• Question then is does Maleness depend on the presence of the Y C-some?
– Answer: No, Bridge showed this not to be the case
Bridges’ Work
• Drosophila have 3 pairs autosomes and 1 pair of sex C-somes
• Observation: Offspring resulting from non-disjunction of X C-some
(meiosis) in females (Result in 2n+1 or 2n-1)
– XXY normal Female
– X0 sterile males
• Conclusion: Y C-some lacks male determining factor, but contains
information essential for fertility
Bridges’ Work
• Observation: Offspring of females containing 3 copies of each C-some
– Wide range of C-some complements occur during meiosis leading to C-some
abnormalities in offspring
• Conclusions: Ratio of X c-somes to the number of haploid sets of
autosomes (A) present determines the sex of drosophila
– > 1.0= Normal Females
– < 0.5= Normal Males
– Between 0.5 and 1.0= Intersex
Dosage Compensation
• Again males contain only half of the genetic material on the X c-some
• Do they compensate for this like humans?
– No, X C-some inactivation is not observed
• Instead male X-genes are transcribed at twice the level as female X-genes
– Master regulator Sxl is inactivated in males (other genes activated) causing
enhanced X gene activity
– Sxl is active in females to inactivate male-specific autosome gene(s)
Drosophila Mosaics
• Appearance of a unique fruit fly
– Half of body expressed mutant phenotype (white eyes and miniature wing), while
other side expressed wild phenotype
• Other females of this cross were heterozygous for these X-linked genes
• Bilateral Gynandromorph: Half of body developed as male and half as
female
Process to Form Mosaics
• Female zygote (heterozygous for both genes) were to loss one of its X Csomes during the 1st mitotic division
– Two cells would be produced one that was XX (Female) and one X0 (Male)
• Progenitor cells then are responsible for producing one half of the flies
body
– Half would be Male
– Half would be Female
Temperature-Sensitive Sex Determination
• Some species sex is determined not by C-some composition
– Retiles, including all crocodiles, most turtles, and some lizards
• Rather sex is determined according to the incubation temperature of the
eggs during a critical period of embryonic development
– Three distinct patterns of sex development have been observed
3 Patterns of TSD
• Case I: 100% females at higher and 100% males lower temps
• Case II: 100% males at higher and 100% females lower temps
• Case III: 100% females at high and low temps, while males at
intermediate temps
• Important observations
– In all cases, both M/F generated at certain temps
– Pivotal temp (P) is fairly narrow
• <5°C sometimes 1°C
Mechanism of TSD
• Thought to involve steroids (mainly estrogen) and the enzymes involved
in their synthesis
• Temp changes have been shown to alter estrogens, androgens, and
inhibitors of the enzymes controlling their synthesis
– Aromatase converts androgen (male hormone) to estrogen (female hormone)