Sex Determination And Sex Chromosomes PDF

Sex Determination and Sex Chromosomes Chapter 5 1 Reproduction In the biological world, there are a wide range of reproductive modes. – Some are totally asexual. – Some alternate between short periods of sexual reproduction and prolonged periods of asexual reproduction. – Others use sexual reproduct...

Sex Determination and Sex Chromosomes Chapter 5 1 Reproduction In the biological world, there are a wide range of reproductive modes. – Some are totally asexual. – Some alternate between short periods of sexual reproduction and prolonged periods of asexual reproduction. – Others use sexual reproduction exclusively. – Sexual reproduction is the only natural mechanism for producing new members of the species. Meiosis ensures genetic constancy but also gives genotypic/phenotypic variability through segregation, recombination and independent assortment during the production of gametes. 2 Sexual Differentiation A wide range of eukaryotic organisms exhibit phenotypic dimorphism of males and females. Heteromorphic, or sex dissimilar, chromosomes (XY in mammals) characterize one sex or the other in a wide range of species. – Genes rather than sex chromosomes determine the sex of the individual Genes on both sex and on autosomal chromosomes! 3 Sexual Differentiation Plants and animals that contain only male or female reproductive organs are unisexual (dioecious or gonochoric). Plants and animals that contain both male and female reproductive organs are bisexual (monoecious or hermaphroditic) and can produce both male and female gametes. 4 Life Cycles and Sexual Differentiation: Roundworm The nematode worm Caenorhabditis elegans has two sexual phenotypes: – Males, which have only testes – Hermaphrodites, which have both testes and ovaries Testes produce sperm that is stored. Oogenesis does not occur until the adult stage. Self-fertilization occurs in the hermaphrodites and produces primarily hermaphrodite offspring, with less than 1 percent male offspring. – As adults, males can mate with hermaphrodites, producing about half male and half hermaphrodite offspring. Genetic signal for male development comes from X chromosome and autosomes Hermaphrodites have two X chromosomes – Males have only one X chromosome (no Y chromosome) Ratio of X chromosome(s) to autosomes is determinant 5 Figure 5-2 6 X & Y Chromosomes and Sex Determination: Early On The XX/XO Protenor (butterfly) mode of sex determination depends on the random distribution of the X chromosome into half of the male gametes. The presence of two X chromosomes in the zygote results in female offspring. The presence of only one X chromosome results in male offspring 7 X & Y Chromosomes and Sex Determination: Early On In the XX/XY Lygaeus (milkweed bug) mode of sex determination: – female gametes all have an X chromosome. – male gametes have either an X or a Y chromosome. Zygotes with two X chromosomes (homogametous) result in female offspring. Zygotes with one X and one Y chromosome (heterogametous) result in male offspring 8 Figure 5-3 9 X & Y Chromosomes and Sex Determination: Early On Males are not always the heterogametic sex. In some organisms, females are the heterogametic sex. – Some moths, butterflies, most fish, reptiles, amphibians, and one species of plants Notation used: ZZ/ZW – Females are the heterogametic (ZW) sex. – Males are the homogametic (ZZ) sex. 10 The Y Chromosome Determines Maleness The human karyotype revealed that one pair of chromosomes differs in males and females: – Females have two X chromosomes. – Males have one X and one Y chromosome 11 Klinefelter Syndrome Klinefelter syndrome (1/1000 males) – Tall stature, with long arms and legs – Underdeveloped testes and prostate gland, no facial hair – Phenotypically male, infertile, slight breast enlargement, and hips often rounded – Generally, intelligence is within normal range – Usually XXY, or a 47,XXY, 48,XXXY, 49,XXXXY karyotype More than two X chromosomes in Klinefelter causes more sever manifestations, but same phenotypically 12 Turner Syndrome Turner syndrome (1/3000 females) – Female external genitalia and internal ducts but ovaries are rudimentary – Short stature, short neck, flat underdeveloped breasts, broad shield-like chest – Generally, have normal intelligence, may have learning disabilities – 45,XO karyotype – Both Klinefelter and Turner syndromes occur due to nondisjunction during meiosis Nondisjunction: Failure of chromosomes (or sister chromatids) to separate during cell division (more on this in chapter 6) – Frequency is less than that of Klinefelter’s, and this due to substantially more 45, X in utero aborted fetuses 13 Y Chromosome Determines “Maleness” It is due to these actual syndromes that it was determined that the Y-chromosome is responsible for causing maleness!! Even in the presence of multiple X chromosomes in Klinefelter…male phenotypes are produced 14 47, XXX Syndrome (Triplo-X) The abnormal presence of three X chromosomes along with a normal set of autosomes (47,XXX) results in female differentiation (1/1000 live births) Frequently, 47,XXX women are perfectly normal and unaware of condition unless a karyotype is done – They have a tendency to be tall and thin In other cases, underdeveloped secondary sex characteristics, sterility, and intellectual disability occur In rare cases, 48, XXXX (tetra-X) and 49, XXXXX (penta-X)  similar but more pronounced than 47,XXX Extra X-chromosomes can disrupt normal female development 15 47, XYY Condition In 1965 Patricia Jacobs discovered that 9/315 males in a Scottish prison had this condition They were all above average in height and were jailed for violent crimes. 7 of the 9, had subnormal intelligence The only consistently shared characteristic found so far in the 47,XYY karyotype is that such males are over 6 feet tall with subnormal intelligence. 16 Sexual Differentiation in Humans During early embryonic development, the embryo is hermaphroditic—the gonadal phenotype is sexually indifferent. As development continues, gonadal ridges (bipotential gonads) can form either ovaries or testes. – Triggered by presence or absence of Y chromosome 17 The Y Chromosome and Male Development The Y chromosome has at least 75 genes, and the X chromosome has 900–1400 genes. The pseudoautosomal regions (PARs) present on both ends of the Y chromosome share homology with regions on the X chromosome and synapse and recombine with it during meiosis. The presence of such a pairing region is critical to segregation of the X and Y chromosomes during male gametogenesis. 18 The Y Chromosome and Male Development The non-recombining region (95 %) of the Y chromosome is called the male-specific region of the Y (MSY) – Some portions of MSY share homology with the X chromosome, others do not. – It has heterochromatic (highly condensed region) and euchromatic (less condensed region) regions. The SRY (sex-determining region) gene is located adjacent to the PAR of the short arm of the Y chromosome. 19 Figure 5-5 20 Y-Chromosome and Human Males At 6–8 weeks of development, the SRY genes become active in XY embryos. The testis-determining factor (TDF) is a protein encoded by the SRY gene that triggers testes formation. – Present in all mammals Deviations from normal sex determination – Males: with two X chromosomes and no Y, but SRY region attached to X chromosome – Females: with one X chromosome and one Y chromosome are missing the SRY gene. 21 Male : Female = 1:1? The actual proportion of male to female offspring is referred to as the sex ratio. The primary sex ratio reflects the proportion of males to females conceived in a population. The secondary sex ratio reflects the proportion of each sex that is born. Initial results male : female (1969): – Secondary ratio: US Caucasian 1.06 US African American 1.025 Korea 1.15 – Many more males are conceived but also have higher fetal mortality; nevertheless, more males are born than females? Remained so until 2015 New results (2015): PSR is actually 1 but embryonic and fetal mortality for females is higher. 22 Extra X Chromosome Dosage compensation balances the dose of X chromosome gene expression in females and males The inactive X chromosomes are highly condensed, can be observed in stained interphase cells, and are referred to as Barr bodies – Arise from the random inactivation of either the maternal or paternal chromosome – Occur early in embryonic development, and all cellular descendants have the same inactivated chromosome 23 Barr Bodies Regardless of how many X chromosomes a somatic cell possesses, all but one of them are inactivated. (N-1 rule: N is the number of X chromosomes) – No Barr bodies in Turner’s (XO) – One Barr body in Klinefelter’s (XXY) – Two Barr bodies in 47,XXX 24 Figure 5-7 25 X Chromosome Inactivation Although the apparent inactivation explains dosage compensation, it complicates certain perceptions in this matter – Why is Turner syndrome 45,XO not entirely normal? – Why are females with triple or tetra Xs not normal? – Why does an extra X in Klinefelter syndrome (47,XXY) result in the characteristic phenotype? Possible explanations: Inactivation does not take place in early stages of the development of gonadal tissue. Not all X chromosomes are inactivated. – 15% remain active 26 Lyon Hypothesis Inactivation of X chromosome is random. It occurs in somatic cells at an early stage of embryonic development and is then passed on to progeny cells by mitosis. – Heterozygote female mice show mottling coat color for coat color genes on X chromosome. – Calico cats show black and yellow-orange patches of fur color – Human G6PD (glucose 6-phosphate dehydrogenase) is controlled by an X-linked gene. Heterozygous females for different allelic forms of G6PD show X inactivation via gel migration. 27 Mechanism of Inactivation Not very well understood, but somehow the DNA, or the histone proteins, or both get inactivated chemically. A memory is created to keep track of the chemically modified homolog that keeps the same homolog inactivated following chromosome replication and cell division. This process whereby expression of genes on one homolog but not the other is affected is called imprinting. 28 X-Inactivation The X-inactivation center (Xic) is located on the proximal end of the p arm in humans, and its genetic expression occurs only on the X chromosome that is inactivated. – It consists of the X-inactive specific transcript (XIST) gene, which is critical to inactivation. XIST RNA is not translated into a protein It binds to the X chromosome and shields it – Recruits other proteins to create the shield 29 Drosophila Sex Determination The Y chromosome does not determine sex in Drosophila. – But the Y chromosome is needed for fertility. Sex is determined by the ratio of X chromosomes to the haploid sets of autosomes (A). Normal female XX and AA 1:1 Normal male XY and AA 1:2 30 Figure 5-9 31 Drosophila Sex Determination With respect to primary sex determination, male gametes containing one of each autosome plus a Y chromosome result in male offspring because they lack an X chromosome. – Genic Balance Theory: Threshold of maleness is reached when the X:A ratio is 1:2 (X:2A), but the presence of additional X (XX:2A) alters the balance and results in female differentiation. 32 Temperature and Sex Determination The environment, specifically temperature, has a profound influence on sex determination. – Temperature-dependent sex determination (TSD) Although many reptile species do use ZZ/ZW or XX/XY, in others TSD is the norm. For all crocodiles, most turtles, and some lizards, sex determination is achieved according to the incubation temperature of eggs during a critical period of embryonic development. 33 TSD There are three different patterns of temperature sex determination in reptiles Case I: Low temperatures yield 100 percent females, and high temperatures yield 100 percent males. Case II: The exact opposite occurs. Case III: Low and high temperatures yield 100 percent females, and intermediate temperatures yield various proportions of males. – Seen in various species of crocodiles, turtles, and lizards 34 Figure 5-10 35 Temperature and Sex Differentiation This temperature difference is believed to involve steroids (mainly estrogens) and the enzymes involved in their synthesis. – One enzyme in particular, aromatase, converts androgens (male hormones such as testosterone) to estrogens (female hormones such as estradiol). Sex-determining mechanisms involving estrogens seem to be characteristic of non-mammalian vertebrates. 36