3.1 How sex is determined #
3.1.1 Four chromosomal systems #
The letters record which chromosome differs and which sex makes two kinds of gametes. The switch that reads the difference is not the same in a fly, a mammal, and a bird.
Chromosomal Crossover
| System | Usual female | Usual male | Heterogametic sex | What is read | Familiar in |
|---|---|---|---|---|---|
| XY | XX | XY | Male | Mammals: SRY on the Y. Drosophila: X-to-autosome ratio, not the Y | Mammals; Drosophila |
| XO | XX | XO | Male | One X versus two | Grasshoppers. In C. elegans, XO is male and XX is hermaphrodite |
| ZW | ZW | ZZ | Female | Not SRY. In birds, dose of Z-linked DMRT1 is the leading switch | Birds; butterflies and moths |
| Haplodiploidy | Diploid | Haploid | Neither, in the XY sense | Fertilised eggs female; unfertilised eggs male | Bees, ants, wasps |
In Drosophila, XO is a sterile male and XXY is female. In humans, 45,X has a female phenotype and 47,XXY a male phenotype, because functional SRY decides the gonad. An XX person with SRY translocated to an X develops as male; an XY person without functional SRY develops as female. The fly rule and the human rule must not be swapped. A haploid male has no genetic father and transmits his whole genome to each daughter. What that relatedness implies for social insects is Evolutionary Biology.
202208 Chromosomal Structural Abnormality Robertsonian Translocation Icon
3.2 X-linked inheritance #
The study of X-linked inheritance provides fundamental principles governing cellular architecture, molecular interactions, and physiological regulation.
X Linked Recessive
3.2.1 White eye in Drosophila #
Morgan’s white eye (1910) is X-linked and recessive. Males are hemizygous: the Y lacks the locus, so the single allele shows. Red-eyed females × white-eyed males give a red F1. In the F2 every daughter is red, because she receives the father’s X^{w⁺}, and half the sons are white, because they receive the heterozygous mother’s X. Overall the ratio is about 3:1, and the white flies are male.
The reciprocal cross does not match. White-eyed females × red-eyed males give red-eyed daughters and white-eyed sons. Sons take the mother’s X and daughters the father’s. That criss-cross is the signature of X-linkage. Morgan’s title said sex-limited. The trait is sex-linked: homozygous females show it.
3.2.2 Haemophilia and red–green colour vision #
Haemophilia is the classical human X-linked recessive: clotting factor VIII (F8) or IX (F9). An affected man passes his X to every daughter and his Y to every son, so he has no affected sons by this allele unless the mother also carries it. A carrier passes the mutant X to half her sons and half her daughters. The pedigree running from Queen Victoria has this shape and is used here only as a diagram, not as a clinical history.
Red–green defects are X-linked because the long- and medium-wave opsin genes lie together on the X and mispair. A male has one array. Short-wave (blue) opsin is autosomal, so an isolated blue defect is not this pattern. Heterozygous females are usually unaffected when one working copy supplies a circulating product, or when one normal cell population is enough. Section 3.4 is why “usually” is not “always”.
3.2.3 Why X-linked recessives appear more often in males #
If the recessive allele has frequency q, affected males have frequency about q, because every male who receives it expresses it. Affected females have frequency about q² under random mating (Chapter 9). The ratio of affected males to affected females is about 1/q, large when the allele is uncommon.
Autosomal Recessive Pedigree (1)
No extra male susceptibility is required for that arithmetic. An affected female implies an affected father and a carrier mother, or incomplete recessivity. For a genetically lethal X-linked recessive, many isolated males are also new mutants (Chapter 11).
3.3 The Y chromosome #
3.3.1 What Y-linked inheritance can and cannot do #
A strictly Y-linked allele lies in the male-specific region, which does not recombine with the X. It passes from father to all sons and to no daughters. The region is gene-poor. SRY is the clear sex-determining gene; much of the rest concerns spermatogenesis, and a mutation that blocks sperm removes itself. The pseudoautosomal tips do recombine with the X, so a father can pass those alleles to a daughter. They are not Y-linked. Old claims such as hairy pinnae do not survive the distinction.
A male-only trait that passes through daughters is sex-limited and autosomal until a male-specific locus is shown. Father-to-all-sons, never through a daughter, is the Y-linked pattern, and it is rare.
3.4 Dosage compensation #
3.4.1 Lyonisation, the Barr body, and the calico cat #
Mammals correct X dose by inactivating one X in each XX cell. Lyon (1961): the choice is random early in the embryo and then stable through mitosis, so the adult is a mosaic of clones. The inactive X is the Barr body. Barr-body number is the number of X chromosomes minus one: XX has one, 45,X none, 47,XXY one. XIST RNA coats the future inactive X in cis; the chromatin detail is Molecular Biology. Some genes escape, and pseudoautosomal genes must, because males express them from both X and Y.
An X-linked orange-versus-black locus makes a heterozygous female cat a mosaic of orange and black clones. White patches are a separate, usually autosomal spotting genotype. A calico cat is almost always female; a rare male is expected to be XXY. Where a product stays in the cell, clones that inactivated the wild-type X can show the mutant phenotype, as in the patchy skin of anhidrotic ectodermal dysplasia. A circulating product such as a clotting factor can be supplied by the cells that kept the wild-type X, so the heterozygote usually does not manifest the disease. Skewed inactivation can still reveal it. Flies compensate by up-regulating the single male X, and C. elegans by down-regulating both X chromosomes in the hermaphrodite. The dose problem is shared. Lyonisation is not.
3.5 Key terms, summary, and self-check #
Key terms. SRY; X-to-autosome ratio; haplodiploidy; hemizygous; criss-cross inheritance; pseudoautosomal; Barr body; Lyon hypothesis; XIST; calico; manifesting heterozygote.
Summary. XY, XO, ZW, and haplodiploidy are different devices; flies read X dose and mammals read SRY. X-linked recessives criss-cross and do not pass from father to son; males are affected at about q and females at about q². The male-specific Y goes from father to all sons and carries few genes. XX mammals inactivate one X at random, keep the choice, and are mosaics for cell-autonomous alleles.
Self-check.
1. Why is an XO fly male, while 45,X in humans has a female phenotype?
2. Which white-eye reciprocal cross gives white-eyed sons and red-eyed daughters in the F1?
3. For an X-linked recessive with q = 0.01, what are the frequencies of affected males and females?
4. Why does father-to-all-sons transmission describe few human genes?
5. How many Barr bodies has a 47,XXY cell, and why can a male calico cat point to that karyotype?
