Ch 7 Sex Determination and Sex Chromosomes

Karyotype and basic terminology

• Karyotype overview: 22 pairs of autosomes plus a pair of sex chromosomes; the last pair shown as the sex chromosomes. In the example, a male has one X (larger) and one Y (smaller) chromosome. The Y chromosome is specifically discussed later.
• Terminology:
  • Primary sexual differentiation = gonads, where gametes are produced.
  • Secondary sexual differentiation = the organism’s overall appearance.
  • Most organisms are unisexual (diaches): male and female reproductive organs are in separate individuals.
  • Bisexual or hermaphroditic organisms possess both male and female reproductive organs.
  • Examples: plants often exhibit hermaphroditism.

Life cycles and modes of sex

• Three life-cycle examples illustrating different sex-reproduction strategies:
  1) Organisms with infrequent periods of sexual reproduction (Planidomonas example):

  • Majority of life cycle is haploid (N). Cells divide mitotically to produce more haploid individuals.
  • Under stress (nitrogen depletion), some cells differentiate into gametes (male and female types).
  • Fusion (fertilization) forms a diploid zygote (2N).
  • When conditions are favorable again, meiosis occurs to produce haploid individuals. Most of the time these organisms are haploid vegetative cells.
    2) Organisms with sex structures in different tissues (Zea mays, maize/corn):
  • Diploid sporophyte (2N) dominant; male and female structures are in different tissues.
  • Male part (stamen) meioses produce pollen (male gametophyte; haploid).
  • Female part (pistil/ovule) meioses form haploid female gametes.
  • Result is separation of male and female gamete formation in distinct floral organs.
    3) Hermaphrodites (C. elegans):
  • The majority are hermaphrodites (≈99%), with a very small minority being males (≈1%).
  • In these organisms the X chromosome is involved in sex determination: hermaphrodites carry two X chromosomes; males carry one X chromosome (and no Y in many cases).

• Birds and heterogamety:

  • In birds, the heterogametic sex is female (ZW), while the homogametic sex is male (ZZ).
  • To avoid confusion, notation ZZ (males) and ZW (females) is used; here, females are the heterogametic sex.

Human karyotypes and notation

• Human karyotypes illustrated: normal female (left) and normal male (right).
  • Each has 22 autosomal pairs (44 autosomes) and 2 sex chromosomes.
  • Female: XX; Male: XY.
  • Y chromosome is smaller than X.
• Chromosome count notation:
  • Normal female: total chromosomes = 46; sex chromosome complement XX.
  • Normal male: total chromosomes = 46; sex chromosome complement XY.
• Notation convention for karyotypes:
  • Always present the total number of chromosomes first, then a comma, followed by the sex chromosome complement or aberration (e.g., 46,XX or 46,XY).

Sex-determination disorders (historical and current)

• First recognized human sex-development abnormalities (1940s): Klinefelter syndrome and Turner syndrome.
  • Klinefelter syndrome: 47 total chromosomes with XXY sex chromosome complement (two X chromosomes and one Y).
  • Phenotype: male but sterile; rounded hips and some breast development.
  • Incidence: approximately 1 in 600 male births.
  • Turner syndrome: 45 total chromosomes with a single X chromosome (monosomy X, 45,X).
  • Phenotype: female; sterile; webbed neck, broad chest; usually short stature.
  • Incidence: approximately 1 in 2,000 female births.
• Other common aneuploidies discussed:
  • 47,XXX (Triple X): three X chromosomes; sometimes not detected.
  • 47,XYY: one X and two Y chromosomes; typically taller stature and potential behavioral issues.
• Convention recap:
  • Karyotype notation lists total chromosome number first, then a comma, then the sex chromosome complement or specific abnormality (e.g., 47,XXY; 45,X).

How sex is determined in humans and the underlying genetics

• In humans, the Y chromosome carries the key determinant of maleness.
  • Y chromosome contains the SRY (sex-determining region Y) gene.
  • SRY expression leads to production of testis-determining factor (TDF).
  • Gonads develop into testes under TDF influence.
  • Testes produce two important signals:
  • Müllerian inhibiting hormone (MIH; also called anti-Müllerian hormone, AMH): causes regression of Müllerian ducts.
  • Testosterone: promotes development of Wolffian ducts into male internal genitalia.
  • With Y present, Müllerian ducts regress and Wolffian ducts develop, leading to male differentiation.
• In the absence of the Y chromosome:
  • Gonads develop into ovaries.
  • Müllerian ducts persist and Wolffian ducts regress, leading to female differentiation.
• But there is a specific Y region structure:
  • Pseudoautosomal region (PAR): regions at the ends of X and Y that are homologous and pair/separate during meiosis; this region is depicted at the top and bottom in the visual description.
  • MSY: Male-Specific Region of the Y; contains genes necessary for male development besides SRY.
  • SRY location: within the Y’s sex-determining region; SRY product initiates the cascade toward testis formation.
  • Euchromatin vs heterochromatin:
  • Euchromatin (lighter blue) contains actively transcribed genes.
  • Heterochromatin (dark gray) is highly condensed and transcriptionally inactive.

Drosophila and alternative sex-determination mechanisms

• Drosophila melanogaster (fruit fly) uses X chromosome to autosome (X:A) ratio for sex determination rather than presence/absence of Y:
  • Normal female: X:A ratio is 1:1 (one X per set of autosomes).
  • Normal male: X:A ratio is 1:2 (two sets of autosomes per single X), leading to male development.
  • This demonstrates an X-chromosome counting mechanism that determines sex in Drosophila differently from the mammalian Y-centered system.

Temperature-dependent sex determination in reptiles

• Some reptiles exhibit temperature-dependent sex determination (TSD):
  • A pivotal temperature determines the sex of the developing embryo.
  • Pattern variants include:
  • High temperatures yielding one sex (often females in many species) and low temperatures yielding the other (often males).
  • Some species show the opposite pattern.
  • In some species, only intermediate temperatures produce males; temperatures outside that range yield females.
• Example reference: red-pups (a common example mentioned in the transcript).
• Practical implication: environmental conditions during incubation can determine the sex ratio of the population.

X-linked genes, dosage compensation, and Barr bodies

• X-linked genes reside on the X chromosome; females have two X chromosomes, males have one.
• Dosage compensation is needed to prevent overexpression of X-linked genes in females.
  • In many species (including humans), one X chromosome is inactivated in each cell, forming a Barr body (the inactive X).
  • Barr body formation occurs early in development and is random with respect to which parental X is silenced in each cell.
• Barr body naming and history:
  • Named after Murray Barr and Ewart Bertram who observed Barr bodies in female somatic cells.
• Implications for X-linked traits:
  • In females who are heterozygous for an X-linked allele, some cells express one allele and some express the other due to random X inactivation, leading to mosaic phenotypes.

X-linked pigmentation and calico cats as an illustration of X-inactivation

• Calico cats demonstrate X-linked mosaicism due to X-inactivation:
  • Coat color genes (orange vs black) are on the X chromosome.
  • In females heterozygous for orange and black alleles (X^O/X^B), random X inactivation in different cells leads to patches of color (orange and black) in the same animal.
  • Males, having only one X, show a uniform coat color corresponding to the single X they inherited from the mother.
• In a female with two X chromosomes carrying the same allele (both X^O or both X^B), the cat’s coat is uniformly one color.
• If a female is heterozygous in certain tissues, the pattern can vary across tissues due to the random nature of X inactivation.

Summary of key conventions and concepts

• Karyotype notation examples to memorize:
  • 46,XX (normal female)
  • 46,XY (normal male)
  • 47,XXY (Klinefelter)
  • 45,X (Turner syndrome)
  • 47,XXX (Triple X)
  • 47,XYY (XYY syndrome)
• Core biological concepts:
  • Sex determination in humans is driven by the SRY gene on the Y chromosome, which triggers testis development and downstream hormonal signaling.
  • In the absence of Y, ovaries develop and female internal structures form.
  • The Y chromosome contains regions beyond SRY (MSY) and shares a small region (PAR) with the X for pairing.
  • XXX and XYY are examples of aneuploidies with distinct phenotypic implications.
  • Drosophila uses X:A ratio rather than Y for sex determination.
  • Some reptiles use temperature to determine sex (TSD), with pivotal temperatures defining sexual fate.
  • Dosage compensation via X inactivation creates Barr bodies to balance X-linked gene expression between the sexes.
  • X-inactivation is random and can produce mosaic phenotypes in females (e.g., calico cats).

Connections to broader topics and real-world relevance

• Genetic testing and diagnosis: understanding karyotype notation and sex chromosome abnormalities informs clinical genetics and counseling (e.g., Turner, Klinefelter).
• Developmental biology: SRY/TDF pathway illustrates how a single gene cascade can determine the developmental fate of gonads and downstream sexual phenotypes.
• Evolutionary genetics: multiple sex-determination systems (XY, ZW, X:A ratio, TSD) reveal diversity of strategies for achieving sexual reproduction and how sex chromosomes evolve.
• Ethical and practical considerations (implicit): knowledge of sex determination and chromosomal abnormalities underpins decisions in prenatal screening, medical management, and discussions about fertility and gender-related health issues.

Notable numerical references and formulas to remember

• Human chromosome counts and karyotypes:
  • Autosomes: $22$ pairs (i.e., $44$ autosomes)
  • Sex chromosomes: 1 pair (XX or XY)
  • Total human chromosomes: $46$
• Common aneuploidies:
  • Klinefelter: $47,XXY$
  • Turner: $45,X$
  • Triple X: $47,XXX$
  • XYY: $47,XYY$
• Important gene concept:
  • SRY gene encodes the Testis-Determining Factor (TDF)