Sex determination involves various mechanisms across animal groups. XX-XY (most common): Females = XX (homogametic — all eggs carry X). Males = XY (heterogametic — 50% sperm carry X, 50% carry Y). Examples: humans (44 autosomes + XX/XY), Drosophila melanogaster. Sex determined by Y chromosome (SRY gene in humans). XX-XO: Females = XX. Males = XO (single X, no Y chromosome). Males have one fewer chromosome than females. Examples: grasshopper (Locusta, Schistocerca, Acridium), cockroach (some species), many orthoptera. ZW-ZZ: Females = ZW (heterogametic). Males = ZZ (homogametic). Opposite of XY. Examples: birds (Gallus, Pavo), butterflies (Bombyx mori — silkworm), some fish (Xiphophorus). Haplodiploid: honeybees (Apis). Females = diploid (2n=32) from fertilised eggs. Males = haploid (n=16) from unfertilised eggs by parthenogenesis.

Grasshoppers (Order Orthoptera) use XX-XO sex determination. Chromosome numbers: Females (XX): 2n = 24 (22 autosomes + 2 sex chromosomes = XX). Males (XO): 2n = 23 (22 autosomes + 1 sex chromosome = 1 X, no Y). The single X in males is unpaired during meiosis I — this was the "X body" first observed by Henking in 1891. Gametes produced: Females (XX) produce eggs: 11 autosomes + 1X = 12 chromosomes. Males (XO) produce two types of sperm: 11 autosomes + 1X = 12 chromosomes (50%), OR 11 autosomes + 0X = 11 chromosomes (50%). After fertilisation: 12+12 = 24 (female XX) or 12+11 = 23 (male XO). So sex is determined by the sperm — X-bearing sperm → female, X-lacking sperm → male. Note: no Y chromosome exists in this system.

Humans: 44 autosomes + XX (female) or XY (male). SRY gene (Sex-determining Region Y) on Y chromosome: master switch for male development. Presence of SRY: activates downstream genes → gonadal differentiation to testes → testes produce testosterone and AMH → male phenotype develops. Absence of SRY (XX): ovarian development → female phenotype. SRY evidence: XX individuals with SRY translocation → phenotypically male. XY individuals with SRY deletion → phenotypically female. SRY activates SOX9, which activates other genes including AMH (Anti-Mullerian Hormone). AMH: from Sertoli cells → causes Mullerian duct regression (female reproductive structures absent in males). Testosterone: from Leydig cells → masculinises Wolffian ducts and external genitalia. Chromosomal sex (XX/XY) determines gonadal sex → gonadal sex (hormones) determines phenotypic sex.

Abnormal sex chromosome numbers cause specific conditions. Turner syndrome (45,X or 45,X0): female phenotype. Missing one X. Short stature, webbed neck, primary amenorrhoea (streak gonads), infertility. Normal intelligence. Prevalence: 1 in 2500 female births. Klinefelter syndrome (47,XXY): male phenotype (SRY present). Extra X. Tall stature, gynecomastia (breast development), small testes, infertility, Leydig cell failure (low testosterone). Often mild intellectual disability or learning difficulties. Prevalence: 1 in 1000 male births. Triple X syndrome (47,XXX): female, usually normal fertility. Some learning difficulties. XXY females (rare). XYY syndrome (47,XYY): male, usually tall. Behavioural difficulties sometimes reported but not consistently. Normal fertility. All these conditions result from non-disjunction during meiosis. Klinefelter is the most common sex chromosome aneuploidy.

Drosophila melanogaster uses a different mechanism from humans despite having XX/XY chromosomes. Sex determined by X:Autosome (X:A) ratio, NOT by Y chromosome. X:A = 1.0 (XX, diploid): female. X:A = 0.5 (XY, diploid): male. X:A = 1.5 (XXX, triploid): superfemale (weak, infertile). X:A = 0.67 (XXYY, triploid): intersex. Drosophila XY males: Y chromosome required for male FERTILITY (sperm production) but NOT for sex determination. XO Drosophila: infertile male (sex determined by X:A = 0.5, but Y needed for sperm). Comparison with humans: Humans — Y (SRY) determines maleness. Drosophila — X:A ratio determines sex, Y only needed for fertility. Both are XX-XY externally but the molecular mechanism differs.

The history of sex chromosome discovery: Henking (1891): studying spermatogenesis in Pyrrhocoris (fire bug). Noticed an unpaired chromatin body during meiosis I in males that went to only one pole — called it X body (X = unknown). McClung (1902): studying grasshoppers. Proposed that the accessory chromosome (Henking X body) determines sex. Stevens and Wilson (1905): independently demonstrated XX-XY system in beetles (Tenebrio molitor). Established that sex is chromosomally determined. Morgan (1910): working with Drosophila. Discovered sex-linkage (white eye gene on X chromosome). Proved Sutton-Boveri chromosome theory of heredity. Ford and Hamerton (1956): established human chromosome number = 46. Tjio and Levan (1956): correct count of 46 human chromosomes (previously thought to be 48). Barr and Bertram (1949): Barr body = inactive X in female cells. Lyon (1961): X-inactivation hypothesis.

Sex-linked (X-linked) inheritance: genes on X chromosome. X-linked recessive (colour blindness, haemophilia A and B): more common in males (XY — only one X, so hemizygous). Carrier females (XRXr) are phenotypically normal but pass to sons. X-linked dominant (hypophosphataemia, Rett syndrome): affected females transmit to 50% daughters and 50% sons. Y-linked (holandric) inheritance: Y chromosome genes. Passed from father to ALL sons (never daughters). Examples: H-Y antigen genes, SRY, azoospermia factor (AZF). Autosomal dominant (Huntington disease, Marfan syndrome, achondroplasia): one mutant allele sufficient. Usually in every generation. Autosomal recessive (sickle cell, cystic fibrosis, PKU, albinism): both alleles must be mutant. Heterozygote = carrier. Skips generations. Consanguinity increases risk. Co-dominance (ABO blood groups): both alleles expressed in heterozygote.

Sutton (1902) and Boveri (1902) independently proposed that chromosomes carry genes (Chromosomal Theory of Heredity / Sutton-Boveri Theory). Key observations supporting the theory: Chromosomes occur in pairs (like Mendel factors/alleles). Homologous chromosomes separate during meiosis (like alleles). Chromosomes are inherited from both parents (like factors). The number of chromosomes is small but genes are many → genes must be linked (Sutton correctly predicted linkage). Morgan (1910) confirmed using Drosophila: sex-linked white eye gene on X chromosome, crossing over between linked genes, creation of genetic maps (linkage groups). The chromosome theory explained: Mendel laws (segregation = chromosome segregation, independent assortment = independent chromosome pairs), sex determination, sex linkage, and exceptions to independent assortment (linkage groups).