Sex Determination and Sex Chromosomes Active Lecture PowerPoint® Presentation for Essentials of Genetics Seventh Edition Klug, Cummings, Spencer, Palladino Chapter 5 Sex Determination and Sex Chromosomes Copyright © 2010 Pearson Education, Inc.

Outline Life Cycles & Sexual Differentiation Chlamydomonas Maize (Zea mays) Caenorhabditis elegans Humans Drosophila Reptiles

Asexual reproduction vs. Sexual reproduction Which organisms have asexual reproduction? Which organisms have both asexual and sexual modes of reproduction? Do bacteria have sexes?

Life Cycles Depend on Sexual Differentiation In multicellular organisms, it is important to distinguish between: primary sexual differentiation - involves only gonads where gametes are produced and secondary sexual differentiation - involves overall appearance of organism

Sexual Differentiation Unisexual (dioecious or gonochoric): - individuals contain only male or female reproductive organs Bisexual (monoecious or hermaphroditic): - individuals contain both male and female reproductive organs - can produce both male and female gametes

Life Cycle of Chlamydomonas spend most of life cycle in haploid phase asexually produce daughter cells by mitotic divisions under unfavorable nutrient conditions, certain daughter cells function as gametes Normally produce daughter cells asexually through mitotic divisions. However… under unfavorable nutrient conditions, a primitive form of sexual reproduction occurs.

Life Cycle of Chlamydomonas two gametes that fuse together during mating are not morphologically distinguishable such gametes are called isogametes

Figure 5-1 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 5-1 The life cycle of Chlamydomonas. Unfavorable conditions stimulate the formation of isogametes of opposite mating type that may fuse in fertilization. The resulting zygote undergoes meiosis, producing two haploid cells of each mating type. The photograph shows vegetative cells of this green alga. Figure 5-1 Copyright © 2006 Pearson Prentice Hall, Inc.

Chlamydomonas Mating Chlamydomonas haploid gametes are of two mating types: mt– and mt+ mt– cells can mate only with mt+ cells, and vice versa there are chemical differences between these mating types, though no visible difference exits

Copyright © 2006 Pearson Prentice Hall, Inc. Illustration of mating types during fertilization in Chlamydomonas. Mating will occur only when plus and minus cells are together. (This figure is not in sixth edition) Copyright © 2006 Pearson Prentice Hall, Inc.

Maize (Zea mays) Life Cycle The diploid sporophyte stage predominates Both male and female structures are present on adult plant (monoecious) Thus, sex determination occurs differently in different tissues of same plant During development, certain cells are determined to become male or female structures. Following sexual differentiation into male or female structures, male or female gametes are produced. Figure 5-2 Copyright © 2006 Pearson Prentice Hall, Inc.

Maize (Zea mays) Life Cycle Figure 5-2 The life cycle of maize (Zea mays). The diploid sporophyte bears stamens and pistils that give rise to haploid microspores and megaspores, which develop into the pollen grain and the embryo sac that ultimately house the sperm and oocyte, respectively. Following fertilization, the embryo develops within the kernel and is nourished by the endosperm. Germination of the kernel gives rise to a new sporophyte (the mature corn plant), and the cycle repeats itself. Figure 5-2 Copyright © 2006 Pearson Prentice Hall, Inc.

Caenorhabditis elegans The nematode worm C. elegans has two sexual phenotypes: Males - have only testes Hermaphrodites - have both testes and ovaries Males are X; hermaphrodites are XX C. elegens lacks a Y chromosome. Maleness determined by genes on both the X chromosome and autosomes Ratio of X chromosomes:autosomes determines the sex:Hermaphrodites have a ratio of 1.0 and males 0.5

Caenorhabditis elegans Self-fertilization occurs in hermaphrodites and produces primarily hermaphrodite offspring, with < 1% male offspring As adults, males can mate with hermaphrodites, producing ~½ male and ½ hermaphrodite offspring

Figure 5-3 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 5-3 (a) Photomicrograph of a hermaphroditic nematode, C. elegans; (b) The outcomes of self-fertilization in a hermaphrodite and a mating of a hermaphrodite and a male worm. Figure 5-3 Copyright © 2006 Pearson Prentice Hall, Inc.

X and Y Chromosomes in Sex Determination X and Y chromosomes were first linked to sex determination early in the twentieth century XX/XO (Protenor )mode of sex determination XX/XY (Lygaeus) mode of sex determination

XX/XO (Protenor) Mode of Sex Determination Depends on random distribution of X chromosome into ½ of male gametes The presence of two X chromosomes in zygote results in female offspring The presence of only one X chromosome in zygote results in male offspring http://natureproducts.net/Animals/Insects/Butterflies/Papilio_protenor2.jpg

Figure 5-4a Copyright © 2006 Pearson Prentice Hall, Inc. Figure 5-4 (a) The Protenor mode of sex determination where the heterogametic sex (the male in this example) is XO and produces gametes with or without the X chromosome Figure 5-4a Copyright © 2006 Pearson Prentice Hall, Inc.

XX/XY (Lygaeus) Mode of Sex Determination http://perso.orange.fr/groisy-nature/images/punaiseimage/Lygaeus_saxatilis_050815DSCN4482groisyweb.jpg 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

Figure 5-4b Copyright © 2006 Pearson Prentice Hall, Inc. Figure 5-4 (b) The Lygaeus mode of sex determination, where the heterogametic sex (again, the male in this example) is XY and produces gametes with either an X or a Y chromosome. In both cases, the chromosome composition of the offspring determines its sex. Figure 5-4b Copyright © 2006 Pearson Prentice Hall, Inc.

ZZ/ZW Sex Determination Females are heterogametic (ZW) sex and males are homogametic (ZZ) sex Examples: some birds, fish, reptiles

Sex Determination 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 and one Y chromosome Y chromosome determines maleness in humans

Sex Determination in Humans Figure 5-5 Copyright © 2006 Pearson Prentice Hall, Inc. The Y chromosome determines maleness in humans. Figure 5-5 The traditional human karyotypes derived from a normal female and a normal male. Each contains 22 pairs of autosomes and two sex chromosomes. The female (a) contains two X chromosomes, while the male (b) contains one X and one Y chromosome (see arrows).

Klinefelter Syndrome Persons with Klinefelter syndrome have more than one X chromosome (usually XXY or a 47,XXY karyotype) Occurs 1 in 1000 male births Have male genitalia; feminine sexual development not entirely suppressed Looks like a male, but sterile (testes do not produce sperms), small testes, reduced facial and pubic hair. They are often taller than normal and sterile; most have normal intelligence.

Figure 5-6 Copyright © 2006 Pearson Prentice Hall, Inc. Klinefelter Syndrome Figure 5-6 The karyotypes and phenotypic depictions of individuals with (a) Klinefelter syndrome (47,XXY) and (b) Turner syndrome (45,X). Figure 5-6 Copyright © 2006 Pearson Prentice Hall, Inc.

Turner Syndrome Persons with Turner syndrome usually have a single X chromosome and no Y chromosome (45, X karyotype) Have female genitalia; ovaries are rudimentary They are short, have a low hairline, relatively broad chest and folds of skin on the neck. Occurs 1 in 3000 female births. Have underdeveloped secondary characteristics. Such syndromes provide evidence that the Y chromosome determines maleness. There are no known cases where both X chromosomes are missing, indicating that at least one X is necessary for human development. Presumably, embryos missing both X’s are aborted spontaneously.

Figure 5-6 Copyright © 2006 Pearson Prentice Hall, Inc. Turner Syndrome Figure 5-6 The karyotypes and phenotypic depictions of individuals with (a) Klinefelter syndrome (47,XXY) and (b) Turner syndrome (45,X). Figure 5-6 Copyright © 2006 Pearson Prentice Hall, Inc.

XXX Condition (Poly X females) The presence of three X chromosomes along with a normal set of autosomes (47,XXX) results in female differentiation Frequently, 47,XXX women have no distinctive features other than a tendency to be tall and thin. 1 in 1000 female births Although a few are sterile, many menstruate regularly and are fertile, and slight tendency towards mental retardation may occur Poly X females Triplo-X syndrome; these persons have no distinctive features other than a tendency to be tall and thin. Although a few are sterile, many menstruate regularly and are fertile. The incidence of mental retardation is slightly greater than in the general population.

Table 5-1 Copyright © 2006 Pearson Prentice Hall, Inc. XYY Condition Only consistently shared characteristic found so far in the 47,XYY karyotype is that such males are over 6 feet tall Table 5-1 Copyright © 2006 Pearson Prentice Hall, Inc.

Y Chromosome Y is a unique chromosome that determines sex in mammals. Y chromosome contains far fewer genes than X (Y has about 75 genes, X about 900-1400). Present on both ends of Y chromosome are the so-called pseudoautosomal regions (PARs) PARs share homology with regions on X chromosome and synapse and recombine with it during meiosis The presence of such a pairing region is critical to segregation of X and Y chromosomes during male gametogenesis The remainder of the Y chromosome does not synapse or recombine with the X chromosome, this non recombining region is the calledthe MSY.

Sexual differentiation in humans By the fifth week the human embryo is potentially hermaproditic. There is no phenotypic difference in the gonadal primordia, the tissues that will form the gonad. Gonadal ridge tissue developes to form either the male or female gonads. Primodial germ cells migrate into these ridges. The cortex can develop into an ovary while the medula can develop into a testis. In addition, two sets of undifferntiated ducts are present. Wolffian ducts that will differentiate into male reproductive tract and the Mullarian ducts that will become structure of the female reproductive tract.

Figure 5-7 Copyright © 2006 Pearson Prentice Hall, Inc. Y Chromosome Y chromosome also contains male-specific region of the Y (MSY) This includes Sex-determining region of the Y (SRY) Figure 5-7 The various regions of the human Y chromosome. Some portions of the MSY share homology with genes on X chromosome and some do not. Euchromatin regions contain functional genes and heterochromatin regions lack genes. In humans, the absence of Y chromosome almost always leads to female development. Thus, SRY is absent from X chromosome. SRY is the gene responsible for male sex determination. It encodes a gene product that triggers the undifferentiated embryos to produce testes. At 6-8 weeks the SRY gene becomes active and causes the undifferntiated gonads of the embryo to form testis. Figure 5-7 Copyright © 2006 Pearson Prentice Hall, Inc.

Y Chromosome SRY or a closely related gene determines sex in all mammals. In humans, the absence of Y chromosome almost always leads to female development. Thus, SRY is absent from X chromosome. SRY is the gene responsible for male sex determination. It encodes a gene product that triggers the undifferentiated embryos to produce testes. At 6-8 weeks the SRY gene becomes active and causes the undifferentiated gonads of the embryo to form testis.

Y Chromosome 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: originally derived from the X; nearly identical to region in X called Xq21 X-degenerative region: originally derived from the X; distantly related to parts in X Ampliconic region: no counterpart in X, genes associated with testes development TDF is the master switch, it is a transcription factor that regulates expression of many other genes. Results from David Page’s research on the Y chromosome. Q: In which region is the SRY located?

We’re Getting More Boys!!! Primary sex ratio vs. Secondary sex ratio Ratio of males to females in humans is not 1.0! Why? In theory the XY & XX cross should generate XY (males) to XX (females) in 1:1 ratio. (Do the Punnett square for this). However, in reality this ratio is slightly greater than one, ranging from 1.025 :0.075 Spontaneous abortions are more common in boy fetuses than in girl fetuses. This ratio might be as high as1.2-1.6 at conception, indicating that many more boys than girls are conceived in a population. One hypothesis is that Y chromosome is smaller than X chromosome Y therefore has less mass So, maybe Y-bearing sperm are more motile than X-bearing sperm increasing likelihood of male zygote being produced

Dosage Compensation: Barr Bodies Darkly staining body in female nuclei that is absent in male cells Barr body is an inactivated X chromosome Mechanism for dosage compensation If one X in females in inactivated, dosage of genetic information that can be expressed in males and females is equivalent Females have two X chromosomes, while males have only one. There is the potential for females to produce twice as much of each gene product for all X-linked genes. But this does not happen because of the dose-compensation mechanism that limits the expression of X-linked genes in females. This compensation is achieved by inactivating either one of the X chromosomes. Barr body in female somatic cells is an inactivated X chromosome.

Figure 5-8 Copyright © 2006 Pearson Prentice Hall, Inc. Barr Bodies Female Figure 5-8 Photomicrographs comparing cheek epithelial cell nuclei from a male that fails to reveal Barr bodies (bottom) with a female that demonstrates Barr bodies (indicated by an arrow in the top image). This structure, also called a sex chromatin body, represents an inactivated X chromosome. Male Figure 5-8 Copyright © 2006 Pearson Prentice Hall, Inc.

Occurrence of Barr Bodies One inactivated None inactivated Figure 5-9 Barr body occurrence in various human karyotypes, where all X chromosomes except one are inactivated. N is the total number of X chromosomes present 45, X – Turner syndrome 46, XY –Normal male 46, XX –Normal female 47,XXY – Klinefelter males Still the Turners females (45,X), 47,XXX and 48,XXXX are not normal. Why? As much as 15% of human x-chromosomal genes escape inactivation. Excessive expression of certain X-linked genes still might occur despite apparent inactivation of additional X chromosomes. Two inactivated Three inactivated

The Lyon Hypothesis The inactivation of X chromosomes occurs randomly in somatic cells at a point early in embryonic development Once inactivation has occurred, all progeny cells have same X chromosome inactivated Makes females mosaics for X-linked traits One X chromosome is of maternal origin and the other paternal origin. Which one is inactivated? Is the same X inactivated in all somatic cells? No. Answers provided by Mary F. Lyon, a British geneticist and collegues working on mouse coat color.

Figure 5-10 Copyright © 2006 Pearson Prentice Hall, Inc. Calico cat Tortoiseshell cat Figure 5-10 (a) A calico cat, where the random distribution of orange and black patches illustrates the Lyon hypothesis. The white patches are due to another gene; (b) A tortoiseshell cat, which lacks the white patches characterizing calicos. Calico & tortoiseshell cats have orange and black patches, Orange parts express the color allele in one X chromosome and black parts express the color allele in the other chromosome. Such color patterns do not exist in males because all their cells contain the single maternal X chromosome. Therefore, calico and tortoiseshell cats are always females. Figure 5-10 Copyright © 2006 Pearson Prentice Hall, Inc.

Copyright © 2006 Pearson Prentice Hall, Inc. This figure not in the Sixth edition Depiction of the absence of sweat glands (shaded regions) in a female heterozygous for the X-linked condition anhidrotic ectodermal dysplasia. The locations vary from female to female, based on the random pattern of X chromosome inactivation during early development, resulting in unique mosaic distributions of sweat glands in heterozygotes. Figure Depiction of the absence of sweat glands (shaded regions) in a female heterozygous for the X-linked condition anhidrotic ectodermal dysplasia. The locations vary from female to female, based on the random pattern of X chromosome inactivation during early development, resulting in unique mosaic distributions of sweat glands in heterozygotes. Q: Are females homozygous for X-linked traits mosaics also? Copyright © 2006 Pearson Prentice Hall, Inc.

The Mechanism of Inactivation: Imprinting X-inactivation Center (Xic) Major control unit in humans Expression occurs only on X chromosome that is inactivated Contains four genes X-inactive specific transcript (XIST) Believed to be critical gene in Xic Lacks an extended open reading frame (ORF) RNA product along with other RNA products of Xic genes may coat X chromosome that produced it How does one X chromosome inactivated? A region in human X chromosome called X-inactivation center has been discovered to be the major control unit.

Sex Determination in Drosophila Females are XX & males are XY Unlike in humans, the Y chromosome is not involved in sex determination in Drosophila Ratio of X chromosomes to sets of autosomes (X:A) determines sex 1:1 X Chromosome: sets of autosome ratio = female 1:2 X Chromosome: sets of autosome ratio = male This is known as the Genic Balance theory of Calvin Bridges XO flies lack a Y chromosome, but they are sterile males. Therefore, Y chromosome in Drosophila lacks male-determining factors, but since XO males are sterile, it does contain genetic information essential to male fertility. Calvin Bridges was a student of T. H. Morgan in the early 1920’s

Drosophila Chromosome compositions and sex Figure 5-11 Chromosome compositions, the ratios of X chromosomes to sets of autosomes, and the resultant sexual morphology in Drosophila melanogaster. The normal diploid male chromosome composition is shown as a reference on the left (XY2A). Figure 5-11 Copyright © 2006 Pearson Prentice Hall, Inc.

Sex Determination in Reptiles In many reptiles sex is determined by sex-chromosome composition However, in some reptiles, sex determination is achieved according to incubation temperature of eggs during a critical period of embryonic development Temperature is thought to influence the enzymes involved in production of estrogens and androgens Examples: crocodiles, some turtles and lizards Not only genes can determine sex. The environment, particularly temperature, has a profound influence on sex determination in reptiles. Jurassic Park movie shows this.

Figure 5-12 Copyright © 2006 Pearson Prentice Hall, Inc. Three Different Patterns of Temperature-Dependent Sex Determination in Reptiles Figure 5-12 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 5-12 Three different patterns of temperature-dependent sex determination (TSD) in reptiles, as described in the text. The relative pivotal temperature is crucial to sex determination during a critical point during embryonic development (FT:female-determining temperature; MT:male-determining temperature).

Genetics, Technology & Society (p107) A Question of Gender: Sex selection in humans

Problems Q 32-34 (p113) The Problem of Cat Cloning Cloned Cats are not Copy-Cats !