Unit 5: Sex Determination and Population Genetics

Sex determination governs how the two sexes arise in an individual, while population genetics describes how allele frequencies behave across a breeding group. This section fixes the definitions and quantities the later sections depend on.

• Sex determination: The genetic or environmental mechanism that directs an organism toward a male or female developmental path, usually via a "trigger" (chromosome, gene, or temperature).
• Heterogametic vs homogametic sex: The sex producing two kinds of gametes (heterogametic) versus one kind (homogametic); e.g. human males are XY (heterogametic), females XX (homogametic).
• Genic balance: In some organisms, sex reflects the ratio of X chromosomes to autosome sets (X:A), not the mere presence of a Y.
• Gene pool: The total collection of alleles in a population at a given locus.
• Allele (gene) frequency: Proportion of a given allele among all alleles at a locus; symbols p and q for two alleles, with p + q = 1.
• Genotype frequency: Proportion of individuals carrying a given genotype; the three diploid classes sum to 1.

II. Mechanisms of Sex Determination

The mechanism differs by taxon: some use a dominant Y-borne switch, others a chromosome ratio, others the environment. Each is defined by its heterogametic sex and its trigger.

A. Mechanism of sex determination in birds, fishes

Birds use a Z–W system opposite to mammals, while fishes show the most varied and labile systems of any vertebrate group.

• ZW system in birds: Females are heterogametic (ZW), males homogametic (ZZ); the egg determines offspring sex.
• Dosage in birds: No single master switch is fully confirmed; the Z-linked gene DMRT1, present in double dose in ZZ males, is the leading candidate driving testis development.
• Chromosomal fishes: Many teleosts have XX/XY or ZZ/ZW systems; the medaka master gene DMY/dmrt1bY on the Y is a duplicated dmrt1 copy triggering maleness.
• Environmental sex determination (ESD) in fishes:
  • Temperature: In some species (e.g. Atlantic silverside), incubation temperature during a critical window skews the sex ratio.
  • Social/pH cues: Sequential hermaphrodites (e.g. clownfish, wrasses) switch sex based on group composition, showing sex is not always fixed at fertilization.

B. Mechanism of sex determination in mammals and Drosophila

These two contrast sharply: mammals use a dominant Y gene, Drosophila uses the X:autosome ratio, so the Y is decisive in one and irrelevant in the other.

1. Mammals (Y-dominant switch):
   • SRY gene: The SRY locus on the Y short arm encodes a testis-determining factor; its presence forces male development regardless of X number.
   • Evidence: XXY (Klinefelter) individuals are male; XO (Turner) individuals are female — sex tracks the Y, not X count.
2. Drosophila (genic balance):
   • X:A ratio: Sex depends on the ratio of X chromosomes to haploid autosome sets.
     • Ratio 1.0 (2X:2A) → female; ratio 0.5 (1X:2A) → male.
   • Y is not determinant: XXY flies are female and XO flies are (sterile) males, proving the Y governs fertility, not sex.
   • Master gene: The ratio is read by Sex-lethal (Sxl), whose ON state initiates the female splicing cascade (Sxl → tra → dsx).

C. Sex differentiation

Sex differentiation is the developmental cascade that converts the determined signal into anatomical and physiological sex.

• Bipotential gonad: The early mammalian gonad can become either testis or ovary; SRY activates SOX9 to divert it to a testis.
• Hormonal control in mammals:
  • Testosterone: From Leydig cells, stabilizes the Wolffian ducts into male internal ducts.
  • Anti-Müllerian hormone (AMH): From Sertoli cells, causes regression of the Müllerian ducts, preventing female structures.
• Default pathway: Without a testis-determining signal, Müllerian ducts persist and the ovarian/female phenotype develops.

D. Chromatin bodies

Chromatin bodies are condensed heterochromatic masses whose count reflects the number of inactivated sex chromosomes.

• Barr body: A darkly staining mass at the nuclear periphery of interphase cells; it is a condensed, inactivated X chromosome.
• N–1 rule: Number of Barr bodies = (number of X chromosomes) − 1.
  • Normal female (XX): one Barr body; normal male (XY): none.
  • XXX: two Barr bodies; XXY (Klinefelter): one.
• Drumstick: A small drumstick-shaped appendage on the nucleus of neutrophils in females, representing the inactive X.

E. Dosage compensation

Dosage compensation equalizes the expression of X-linked genes between the sexes despite their differing X-chromosome numbers.

• Purpose: Prevents females (2X) from producing twice the X-gene product of males (1X).
• Mammalian strategy — X-inactivation (Lyonization):
  • Random silencing: One X per female cell is inactivated early in development, controlled by the XIST RNA, and the choice is clonally inherited.
  • Mosaicism: Produces patchy expression, e.g. the coat colour of tortoiseshell/calico cats.
• Drosophila strategy — hyperactivation: The single male X is transcribed at twice the rate via the MSL (male-specific lethal) complex.
• Caenorhabditis strategy — downregulation: Each X in the XX hermaphrodite is transcribed at half rate, halving total output to match the male.

III. Population Genetics: Allele Frequencies and Their Change

Population genetics treats the population, not the individual, as the unit of study, tracking allele and genotype frequencies over generations. Its baseline is the Hardy–Weinberg equilibrium.

A. Hardy–Weinberg Law

The law states that in a large, randomly mating population free of evolutionary forces, allele and genotype frequencies stay constant across generations.

• Statement: For two alleles at frequencies p and q, genotype frequencies settle in one generation to:

p² + 2pq + q² = 1
where  p + q = 1
p²  = frequency of homozygous dominant (AA)
2pq = frequency of heterozygotes (Aa)
q²  = frequency of homozygous recessive (aa)

• Conditions (assumptions):
  • Large population: No genetic drift.
  • Random mating: No assortative mating for the locus.
  • No mutation, migration, or selection: Allele frequencies are not perturbed.
• Use as null model: Deviation from expected genotype ratios signals that one or more forces is acting.

B. Genotypic and allelic frequencies

These frequencies are the raw measurements from which all population-genetic inference proceeds.

• Allele frequency from counts: Each homozygote contributes two copies, each heterozygote one:

p = (2·N_AA + N_Aa) / (2N)
q = (2·N_aa + N_Aa) / (2N)
N = total individuals

• Worked example: In 100 people, 36 AA, 48 Aa, 16 aa.
  • p = (2·36 + 48)/200 = 120/200 = 0.6
  • q = (2·16 + 48)/200 = 80/200 = 0.4
  • Expected under equilibrium: p²=0.36, 2pq=0.48, q²=0.16 — matching the observed counts, so the locus is at equilibrium.
• Recessive-only case: When heterozygotes are hidden, estimate q = √(q²) from the recessive phenotype frequency, then p = 1 − q.

C. Changes in allelic frequencies

Four forces move allele frequencies away from the Hardy–Weinberg baseline; each acts differently in direction and predictability.

1. Mutation

• Source of new alleles: Mutation is the ultimate origin of genetic variation.
• Slow directional pressure: With forward rate u (A→a) and reverse rate v (a→A), change per generation is small:

Δq = u·p − v·q

• Equilibrium: Frequencies balance when u·p = v·q; because rates (~10⁻⁵–10⁻⁶) are tiny, mutation alone shifts frequencies negligibly per generation.

2. Migration

• Gene flow: Movement of individuals introduces alleles from another population and homogenizes differences.
• One-generation model: With migration rate m and donor frequency q_m:

q' = (1 − m)·q + m·q_m
Δq = m·(q_m − q)

• Effect: Migration always pulls the recipient frequency toward the donor's; sustained gene flow prevents populations from diverging.

3. Selection

• Differential reproduction: Genotypes differ in fitness (w), so favoured alleles rise and disadvantaged ones fall.
• Selection coefficient: s = 1 − w measures the fitness reduction of a genotype.
• Against a recessive lethal: When aa is lethal (s = 1), the recessive allele declines slowly because it hides in heterozygotes:

q_n = q_0 / (1 + n·q_0)
n = number of generations

• Directional outcome: Unlike drift, selection is deterministic and can drive an allele to fixation or loss depending on which genotype is favoured.

4. Genetic drift

• Random sampling error: Chance fluctuation in allele frequencies from generation to generation, strongest in small populations.
• Magnitude: The variance in allele frequency per generation is:

Vq = (p·q) / (2N)
N = effective population size

• Consequences:
  • Fixation/loss: Given enough time, one allele is fixed (frequency 1) and the other lost (frequency 0), reducing heterozygosity.
  • Founder effect: A new colony started by few individuals carries a non-representative allele sample.
  • Bottleneck: A sharp population crash randomly alters and depletes allelic variation among survivors.
• Contrast with selection: Drift is non-directional and unpredictable, whereas selection consistently favours higher-fitness alleles.