Essentials of Genetics Chapter 5 : Sex Determination & Sex Chromosomes (PDF)

Essentials of Genetics Seventh Edition William Klug, Michael Cummings, Charlotte Spencer, Michael Palladino CHAPTER 5 Sex Determination & Sex Chromosomes Pearson Lectures Adapted by Dr. Amin Majdalawieh American University of...

Essentials of Genetics Seventh Edition William Klug, Michael Cummings, Charlotte Spencer, Michael Palladino CHAPTER 5 Sex Determination & Sex Chromosomes Pearson Lectures Adapted by Dr. Amin Majdalawieh American University of Sharjah @2011  Life Cycles Depend on Sexual Differentiation ► In multicellular organisms, it is important to distinguish between: primary sexual differentiation, which involves only the gonads where gametes are produced. secondary sexual differentiation, which involves the overall appearance of the organism including clear differences in such organs as mammary glands and external ganitalia.  Life Cycles Depend on Sexual Differentiation ► Individuals who contain only male or female reproductive organs are unisexual (dioecious or gonochoric). ► Individuals who contain both male and female reproductive organs are bisexual (monoecious or hermaphroditic), and can produce both male and female gametes. ► The term intersex refers to individuals of intermediate sexual differentiation (often sterile).  Life Cycles Depend on Sexual Differentiation ► Some organisms (e.g. Chlamydomonas) spend most of their life cycle in the haploid phase, asexually producing daughter cells by mitotic division. ► Under unfavorable nutrient conditions, however, certain daughter cells function as gametes. ► In such species, the two gametes that fuse together during mating are not usually morphologically distinguishable. ► Such gametes are called isogametes, and species producing them are said to be isogamous. ► Isogametes fusion leads to diploid zygote (withstands unfavorable conditions), which can re-establish the haploidy state if the unfavored condition is relieved. ► Chlamydomonas haploid gametes are of two mating types, mt– & mt+. ► mt– cells can mate only with mt+ cells, and vice versa. ► There are chemical differences between these mating types. Chlamydomonas Mating The life Cycle of Chlamydomonas Figure 5.1  Life Cycles Depend on Sexual Differentiation ► In many plants, there is an alternation between the diploid sporophyte stage and the haploid gametophyte stage. ► These two stages are linked by meiosis and fertilization. ► In maize (Zea mays), a monoecious plant, the sporophyte stage predominates and both male and female structures are present on the adult plant. ► This indicates that sex determination must occur differently in different tissues of the same plant. The Life Cycle of Maize (Zea mays) Figure 5.2  Life Cycles Depend on Sexual Differentiation ► The nematode worm Caenorhabditis elegans has two sexual phenotypes: Males, which have only testes Hermaphrodites, which have both testes and ovaries ► Self-fertilization (egg and sperm from the same organism) occurs in the hermaphrodites and produces primarily hermaphrodite offspring, with less than 1% male offspring. ► As adults, the males can mate with the hermaphrodites, producing about half male and half hermaphrodite offspring. ► Sex determination in C. elegans results from the presence of only one X chromosome in the males and two in the hermaphrodites. Self-Fertilization & Cross-Fertilization in C. elegans Figure 5.3  X and Y Chromosomes Were First Linked to Sex Determination Early in the Twentieth Century ► The XX/XO (butterfly, Protenor) 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. ► So, there is NO Y chromosome! Protenor Mode Figure 5.4a  X and Y Chromosomes Were First Linked to Sex Determination Early in the Twentieth Century ► The XX/XY (milkweed bug, Lygaeus) mode of sex determination: female gametes all have 2 X chromosomes male gametes have 1 X chromosome & 1 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. Lygaeus Mode Figure 5.4b Protenor & Lygaeus Modes of Sex Determination Figure 7.5  X and Y Chromosomes Were First Linked to Sex Determination Early in the Twentieth Century ► The ZZ/ZW sex determination (most birds, reptiles, amphibians, etc): females are the heterogametic (ZW) sex males are the homogametic (ZZ) sex ► So, this is opposite to XX/XY mode of sex determination. X and Y Chromosomes Were First Linked to Sex Determination Early in the Twentieth Century Does the Y chromosome cause maleness? Does only 1 X chromosome cause maleness? Do 2 X chromosomes cause femaleness? Answer comes from examining Klinefelter and Turner syndromes Klinefelter XXY Turner X  X and Y Chromosomes Were First Linked to Sex Determination Early in the Twentieth Century ► Both conditions result from nondisjunction (i.e. chromosomes don’t segregate properly during meiosis). ► Klinefelter: XXY results in male offspring. ► Turner: X results in female offspring. ► So, maleness is controlled by having the Y chromosome. ► XXXY, XXYY etc. are also males! (How is it possible to get XXXY and XXYY genotypes?)  The Y Chromosome Determines Maleness in Humans ► The human karyotype revealed that one pair of chromosomes differs in males and females: females have two X chromosomes males have one X chromosome and one Y chromosome Female Male Figure 5.5  The Y Chromosome Determines Maleness in Humans ► Persons with Klinefelter syndrome have: male genitalia more than one X chromosome (usually XXY, or a 47,XXY karyotype) ► Persons with Turner syndrome usually have: female genitalia a single X chromosome no Y chromosome (X, or a 45,X karyotype) ► Such syndromes provide evidence that the Y chromosome determines maleness. Klinefelter Syndrome & Turner Syndrome Klinefelter XXY Turner X Figure 5.6  Klinefelter Syndrome ► Klinefelter syndrome results in: Rudimentary testes that don’t produce sperm Slight breast enlargement Round hips Less hair on the face/body Social development problems The extra X chromosome does have an effect.  Turner Syndrome ► Turner syndrome results in: Rudimentary ovaries Short stature Folds of skin on the neck Small breasts “Shield-like” chest So, lack of an X chromosome in females does have an effect.  The Y Chromosome Determines Maleness in Humans ► The presence of three X chromosomes along with a normal set of autosomes (47,XXX) results in female differentiation. ► Frequently, 47,XXX women are perfectly normal. ► In some cases, underdeveloped secondary sex characteristics, sterility, and mental retardation may occur. ► The only consistently shared characteristic found so far in the 47,XYY karyotype is that such males are over 6 feet tall. ► The Y chromosome has far fewer genes than the X chromosome.  Triple X Syndrome (XXX Syndrome) ► Females with XXX genotype: Often normal, but can have:  Underdeveloped secondary sexual characteristics  Sterility  Mental retardation So, additional X chromosomes can have a negative effect.  XYY Syndrome ► XYY males often (but not always) have: Low intelligence Tall Behavior problems Chance of ending up in jail or mental institutions So, additional Y chromosome can have a negative effect.  The Y Chromosome Determines Maleness in Humans ► Present on both ends of the Y chromosome are the pseudoautosomal regions (PARs) that share homology with regions on the X chromosome (synapse & 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. ► Y chromosome contains: the male-specific region of the Y (MSY) a sex-determining region of the Y (SRY) ► The testis-determining factor (TDF) is a protein encoded by a gene in the SRY that triggers testes formation. ► The MSY consists of three regions: X-transposed region X-degenerative region ampliconic region Human Y Chromosome Figure 5.7  The Ratio of Males:Females in Humans is not 1.0 ► Primary sex ratio reflects the proportion of males to females conceived in a population. ► Secondary sex ratio reflects the proportion of each sex that is born. ► In 1969, studies demonstrated that secondary sex ratios among different populations were greater than 1. The Ratio of Males:Females in Humans is not 1.0 Since males produce ½ X and ½ Y gametes there should be an equal number of male and female babies produced, Is this the case? No! Actual number of boys born is more than 1:1 ratio of boys:girls 1.06 :1 USA whites 1.03:1 USA blacks 1.15:1 Korea (1.02-1.08):1 Worldwide The Ratio of Males:Females in Humans is not 1.0 What about fertilization? Are more female fetuses being spontaneously aborted? No! More male fetuses are spontaneously aborted! If fertilization = birth, male:female ratio would be (1.08-1.6):1 The Ratio of Males:Females in Humans is not 1.0 Why are there more male fertilizations? The Y chromosome is lighter than the X chromosome Why so many male spontaneous abortions? Unlike females, males only have 1 X chromosome, if a key development gene on this is faulty, fetus has no functioning homologous chromosome  Dosage Compensation Prevents Excessive Expression of X-Linked Genes in Humans & Other Mammals ► Dosage compensation balances the dose of X chromosome gene expression in females and males. ► The inactive X chromosome is highly condensed, can be observed in stained interphase cells, and is referred to as Barr body. Dosage Compensation Prevents Excessive Expression of X-Linked Genes in Humans & Other Mammals Figure 5.9  Dosage Compensation Prevents Excessive Expression of X-Linked Genes in Humans & Other Mammals ► The Lyon hypothesis states that X-inactivation occurs randomly in somatic cells (i.e. which X becomes inactivated (maternal or paternal) is a random event). ► This is evident in the calico cat (mosaic phenomenon). Figure 5.10  Dosage Compensation Prevents Excessive Expression of X-Linked Genes in Humans & Other Mammals ► Anhidrotic ectodermal dysplasia is a condition in females in which the active X chromosome in certain tissues carries a mutated gene that blocks the formation of sweat glands in patches of tissue over the surface of the body.  The Mechanism of Inactivation: Imprinting ► In chromosome inactivation, either the DNA and/or its associated proteins (histones) is modified such that most genes on the chromosome are silenced. ► Whatever the modification, the same chromosome remains inactivated with every cycle of DNA replication & cell division (memory!) ► Such an event whereby gene expression from one chromosome homolog, but not the other, is affected is called “impriniting”. ► The X-inactivation center (Xic) is “active” on the inactive X chromosome. ► Xic consists of 4 genes, the most influential of which is the X-inactive specific transcript (XIST) gene. Many questions remain unanswered regarding the exact mechanism of chromosome inactivation.  The Ratio of X Chromosomes to Sets of Autosomes Determines Sex in Drosophila ► Unlike in humans, the Y chromosome in Drosophila does NOT determine the sex. ► XXY flies are normal females, while XO flies are sterile males! ► So, the Y chromosome in Drosophila lacks male-determining factors. ► However, the Y chromosome in Drosophila contains genes that are essential for fertility since XO flies are sterile males.  The Ratio of X Chromosomes to Sets of Autosomes Determines Sex in Drosophila ► In mid 1910s, Calvin Bridges realized that the critical factor in determining sex in Drosophila is the ratio of X chromosomes to the number of haploid sets of autosomes present. Normal (2X:2A) and triploid (3X:3A) females are fertile (X:A ratio is 1.0) (3X:2A) females are sterile (X:A ratio is NOT 1.0) ► So, what are supposed to be “superfemales” are most likely infertile, and hence, they are more appropriately called “metafemales”! ► What about males? Normal (XY:2A) and sterile (XO:2A) males have an X:A ratio of 0.5. (XY:3A) males are infertile (X:A ratio is 0.33) (metamales). ► Flies with an X:A ratio between 0.5 and 1.0 express BOTH male and female morphologies and they are sterile (intersexes). ► The “genic balance theory” explains this mode of sex determination, in which a threshold for maleness is reached at a specific X:A ratio. The Ratio of X Chromosomes to Sets of Autosomes Determines Sex in Drosophila Figure 5.11  Temperature Variation Controls Sex Determination in Reptiles ► For all crocodiles, most turtles, and some lizards, sex determination is set according to the incubation temperature of eggs during a critical period of embryonic development. ► Males and females are genetically the same! Sex is temperature-dependent. ► There are three different patterns of temperature-dependent sex determination in reptiles. Temperature-Dependent Sex Determination in Reptiles Figure 5.12  Temperature-Dependent Sex Determination in Reptiles How does this occur? ► Aromatase converts androgens (male hormones) to estrogens (female hormones). ► Such hormones in these reptiles regulate formation of testes/ovaries. Is protein transcription of aromatase gene temperature-dependent?  Global Warming and Sex Determination ► Eulamprus tympanum Australian lizard lives on mountain tops. ► The female regulates body temperature to determine offspring’s sex (through sunning). Global warming → warmer temp. → all males being born?!  Sex Determination & Pollutants ► Polychlorinated biphenyls (PCBs) pollutants may mimic estrogens for some temperature-dependant organisms, like turtles and crocodiles. ► PCB pollutants may cause females to develop even though the eggs are placed under temperatures where males normally develop. ► Sperm counts in human males in Western countries declined about 40% between the years 1938 and 1990, possibly due to exposure to estrogens in the environment (endocrine disrupters).