Sex Determination & Chromosomes

Chapter 5: Sex Determination and Sex Chromosomes

• Eukaryotic organisms can exhibit phenotypic dimorphism between males and females
• Heteromorphic or sex chromosomes (ex. XY in mammals) characterize one sex in a species
• Genes, present on sex or autosomal chromosomes, actually determine an individual's sex

Life Cycles and Sexual Differentiation

• It is important to distinguish between primary and secondary sexual differentiation in multicellular organisms
• Primary sexual differentiation involves the gonads, where gametes are produced
• Secondary sexual differentiation involves the overall appearance of the organism, like mammary glands and external genitalia
• Plants and animals with only male or female reproductive organs are called unisexual (dioecious or gonochoric)
• Plants and animals with both male and female reproductive organs are called bisexual (monoecious or hermaphroditic)

Chlamydomonas Sexual Reproduction

• Chlamydomonas are green algae that spend their life cycle in a haploid phase
• They asexually produce daughter cells using mitotic division
• Under unfavorable nutrient conditions, Chlamydomonas daughter cells can function as gametes
• When acting as gametes, two gametes fuse together during mating
• Chlamydomonas gametes that are not morphologically distinguishable from each other are known as isogametes
• There are two mating types of Chlamydomonas haploid gametes: mt- and mt+
• mt- cells can only mate with mt+ cells, and vice versa
• Four haploids are produced through meiosis, also known as zoospores
• Chemical differences exist between the two mating types

Sex Determination in Maize

• In maize (Zea mays), the diploid sporophyte stage predominates, with both male and female structures on the adult plant
• For maize, sex determination occurs differently in different tissues of the same plant
• In nonseed plants the haploid gametophyte phase predominate, but the reverse is true for seed plants
• The stamens (tassel) produce mature male microgametophyte (pollen grain), which contain two haploid sperm nuclei
• The pistil produces four haploid female megaspores where only one survives
• The surviving megaspore divides mitotically three times to produce a total of eight haploid nuclei enclosed in the embryo sac
• Two nuclei unite to produce the endosperm during division
• In maize, upon fertilization, one of the two sperm nuclei unites with the haploid oocyte, and the other sperm unites with the two endosperm nuclei
• Double fertilization yields the diploid zygote nucleus, the triploid endosperm nucleus, which give rise to a corn kernel that germinates (sporophyte)
• Certain mutant genes (ts1 and ts2) can cause sex reversal in maize
• When homozygous, mutations classified as tassel seed (ts) interfere with tassel production, and induce female structure production
• Recessive mutations silkless (sk) and barren stalk (ba) interfere with pistil development, resulting in plants with only male-functioning reproductive organs

C. Elegans Sexual Phenotypes

• The nematode worm Caenorhabditis elegans has two sexual phenotypes: males and hermaphrodites
• Males have only testes
• Hermaphrodites have both testes and ovaries
• In hermaphrodites, testes produce sperm that is stored
• Also in hermaphrodites, ovaries are produced but oogenesis does not occur until the adult stage is reached
• Self-fertilization occurs in hermaphrodites and produces primarily hermaphrodite offspring, with less than 1% male offspring
• Adult males can mate with hermaphrodites can produce about half male and half female offspring
• C. elegans male lacks a Y chromosome but has 1 X chromosome
• Hermaphrodites have 2 X chromosomes
• The ratio of X chromosomes to the number of sets of autosomes determines the sex of these worms
• A ratio of 1.0 (two X chromosomes and two copies of each autosome (5AA; XX)) results in hermaphrodites
• A ratio of 0.5 (5AA; X0) results in males

Chromosomes and Sex Determination

• XX/XO Protenor (butterfly) mode depends on the X chromosome's random distribution into half of the male gametes
• The presence of two X chromosomes in the zygote results in female offspring (14 chromosomes, including two X chromosomes)
• The presence of only one X chromosome results in male offspring (13 chromosomes, including one X chromosome)
• In the XX/XY Lygaeus mode of sex determination, female gametes all have an X chromosome
• Additionally, 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
• Males are not always the heterogametic sex; in some organisms, females are the heterogametic sex
• The notation ZZ/ZW is used in such cases
• Females are the heterogametic (ZW) sex
• Males are the homogametic (ZZ) sex

Y Chromosomes Determine Maleness

• Human karyotypes reveal one pair of chromosomes that differs in males and females
• Females have two X chromosomes
• Males have one X and one Y chromosome

Klinefelter Syndrome

• Klinefelter syndrome affects 1/660 males
• Includes being tall, with long arms and legs, and underdeveloped testes and prostate gland with no facial hair
• Phenotypically male, infertile, with slight breast enlargement, and hips often rounded
• Affected individuals have normal intelligence but may be slow learners
• Usually an XXY, or a 47,XXY, 48,XXXY, 49,XXXXY karyotype

Turner Syndrome

• Turner syndrome affects 1/2000 females
• Includes feale external genitalia and internal ducts but ovaries are undeveloped
• Affected individuals have short stature, skin flaps on back of neck, flat underdeveloped breasts, broad shield-like chest
• Generally have normal intelligence, but may have learning disabilities
• Includes a 45,XO karyotype
• Both Klinefelter and Turner syndromes occur due to nondisjunction during meiosis

Additional Sex Chromosome Anomalies

• 47,XXX Syndrome (Triplo-X_) involves the abnormal presence of three X chromosomes along with a normal set of autosomes (47,XXX)
• Leads to female differentiation (1/1000 live births)
• 47, XXX women are often perfectly normal and unaware of their condition
• In some cases, there can be underdeveloped secondary sex characteristics, sterility, and mental retardation
• The extra X-chromosome can disrupt normal female development
• 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

Y Chromosome Development

• The Y chromosome has at least 75 genes, and the X chromosome has 900-1400 genes
• The pseudoautosomal regions (PARs) located on both ends of the Y chromosome share homology with regions on the X chromosome
• The pseudoautosomal regions synapse and recombine with the X chromosome during meiosis
• The presnce of such a pairing region is critical to segregation of the X and Y chromosomes during male gametogenesis
• The nonrecombining region of the Y (NRY) chromosome is called the male-specific region of the Y (MSY)
• Some portions of MSY share homology with the X chromosome, others do not
• MSY has euchromatic (functional genes) and heterochromatic regions (nonfunctioning_genes)
• The SRY (sex-determining region) is located adjacent to the PAR of the short arm of the Y chromosome

Male Specific Region Y Types

• MSY, found exclusively on the Y chromosome, is known as the male-specific region
• MSY represents 23 million base pairs
• MSY is divided into three regions:
  • The X-transposed region (15 percent of MSY) maintains 98.78% homology between the X and Y
  • The X-degenerative region (20 percent) houses housekeeping genes needed for basic cellular function
  • The Ampliconic region (30 percent) encodes proteins specific to development and function of testis

Human Sexual Differentiation

• During early embryonic development, the embryo is hermaphroditic, where the gonadal phenotype is sexually indifferent
• As development continues, gonadal ridges can form either ovaries or testes (bipotential gonads)
• The determination of ovaries or testes is triggered by presence or absence of Y chromosome
• As development progress, primordial germ cells migrate to gonadal ridges
• The outer cortex develops into ovary and the inner medulla develops into testis
• At 6-8 weeks of development, the sex-determining region (SRY) genes become active in XY embryos
• The testis-determining factor (TDF) is a protein encoded by a gene in the SRY that triggers testes formation
• TDF is present in all mammals
• TDF is considered the transcription factor that behaves as a master switch controlling the genes involved in sexual differentiation

Sex Ratio

• 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 expected in a population
• The secondary sex ratio reflects the proportion of each sex that is born
• Y chromosome is smaller than an X chromosome and contains less mass
• It has been speculated that Y-bearing sperm are more motile than X-bearing sperm, resulting to a male zygote

Dosage Compensation

• Dosage compensation prevents excessive expression of X-Linked genes in humans and other mammals
• Dosage compensation is a genetic mechanism
• Balances dose of X chromosome gene expression levels in males and females
• Prevents excessive expression of X-linked genes in humans and other mammals
• The inactive X chromosomes in a female somatic cell are highly condensed
• These chromosomes are observed in stained interphase cells, and are referred to as Barr bodies
• Barr bodies arise from the random inactivation of either the maternal or paternal chromosome
• Barr bodies occur early in embryonic development, and all cellular descendants have the same inactivated chromosome
• Barr bodies can also occur in males when there is an abnormality and the male is XXY instead of the normal XY
• In somatic cells, all but one of the X-chromosomes is 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
• Lyon Hypothesis
  • Inactivation of X chromosome is random
  • Occurs in somatic cells at an early stage of embryonic development and is then passed on to progeny cells by mitosis
• Xic and XIST
  • Xic: X inactivation center is:
    • Active only on inactive X
    • Has X-inactive specific transcript (XIST) gene critical for X inactivation
• Tsix and Xite play important roles in X chromosome inactivation

Drosophila Sex Determination

• The Y chromosome does not determine sex in Drosophila
• It is needed for fertility
• Sex is determined by the ratio of X chromosomes to the haploid sets of autosomes (A)
• Normal female contain AA and XX chromosomes at a 1:1 ratio
• Normal male contain AA and XY chromosomes at a 1:2 ratio
• With respect to primary sex determination, male gametes contain one of each autosome plus a Y chromosome leades to male offspring due to the lack of an X chromosome
• Genic Balance Theory
  • Threshold of maleness is reached when the X:A ratio is 1:2 (X:2A)
• An additional X (XX:2A) chromosome alters the balance and differentiation to be female

Temperature Variation

• 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
• Sex determination is profoundly influenced by the environment, specifically temperature using a process known as temperature-dependent sex determination (TSD)
• Reptile species use ZZ/ZW or XX/XY, but in others TSD becomes the norm
• 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
• Temperature is believed to involve steroids, mainly estrogens, and the enzymes involved in their synthesis
• One enzyme, aromatase, converts androgens to estrogens
• Sex-determining mechanisms involving estrogens seem to be characteristic of nonmammalian vertebrates