Inheritance

📚The biology

Meiosis

Haploid (n) cells have one set of chromosomes; diploid (2n) cells have two. Homologous chromosomes are a matching pair, one from each parent, with the same genes at the same loci — though not necessarily the same alleles.

A reduction division is necessary because fertilisation doubles the chromosome number. Without halving it during gamete formation, the number would double every generation. Meiosis therefore produces haploid gametes from diploid cells, in two divisions.

Names of the stages are required — prophase I, metaphase I, anaphase I, telophase I, then prophase II, metaphase II, anaphase II, telophase II — but not the sub-divisions of prophase I. The essential difference from mitosis:

• In prophase I, homologous chromosomes pair up and crossing over occurs at chiasmata: sections of chromatid are exchanged between homologues, producing new combinations of alleles on a chromosome.
• In metaphase I, homologous pairs line up on the equator, and the orientation of each pair is random and independent of the others — independent assortment.
• In anaphase I, whole chromosomes (still two chromatids) are separated, one of each pair to each pole. This is the reduction to haploid.
• The second division separates sister chromatids, as in mitosis.

Three sources of variation, and questions usually want all three: crossing over, independent assortment, and the random fusion of gametes at fertilisation, which combines two already-varied haploid sets.

The vocabulary

• Gene — a length of DNA coding for a polypeptide. Locus — its position on a chromosome. Allele — a version of a gene.
• Genotype — the alleles present. Phenotype — the observable characteristics, produced by genotype and environment.
• Homozygous — two identical alleles. Heterozygous — two different alleles.
• Dominant — expressed in the heterozygote. Recessive — expressed only in the homozygote. Codominant — both alleles are expressed in the heterozygote, so the phenotype shows both.
• Linkage — two genes on the same chromosome, so their alleles tend to be inherited together. Test cross — crossing an individual of unknown genotype with a homozygous recessive, to reveal the unknown from the offspring.

Writing a genetic diagram

Marks are given for the layout as well as the answer, so use the same structure every time: parental phenotypes, parental genotypes, gametes (circled), a Punnett square, offspring genotypes, offspring phenotypes and ratio. Define your symbols first. Use a capital and its own lower case for dominance (A, a); for codominance and multiple alleles use a base letter with superscripts, as in C^R and C^W; for sex linkage always write the alleles on the X, as X^HY.

Ratios to recognise, and what they signal:

• 3:1 — monohybrid F₂, both parents heterozygous.
• 1:2:1 — monohybrid F₂ with codominance, since the heterozygote is distinguishable.
• 1:1 — a test cross, or a heterozygote crossed with a homozygous recessive.
• 9:3:3:1 — dihybrid F₂, both parents heterozygous for two unlinked genes.
• 1:1:1:1 — dihybrid test cross with unlinked genes.
• Anything close to 9:7, 12:3:1, 13:3, 15:1 — a modified dihybrid ratio, which means epistasis: one gene is affecting the expression of another. You are not required to know which ratio goes with which type of epistasis.
• A dihybrid cross giving far more parental types than expected and very few recombinants — autosomal linkage. The genes are on the same chromosome, so they do not assort independently; the few recombinants arise by crossing over.

Sex linkage

Genes on the X chromosome have no equivalent on the much shorter Y. A male has only one allele, so he expresses it whether dominant or recessive — he cannot be heterozygous, and the terms homozygous and heterozygous do not apply to him for X-linked genes. This is why X-linked recessive conditions such as haemophilia and red-green colour blindness are far commoner in males, and why an affected male passes the allele to all his daughters (who become carriers) and none of his sons.

The chi-squared test

Use it to test whether a difference between observed and expected frequencies is significant, or is within what chance alone could produce.

Set out a table with columns for O, E, O − E, (O − E)² and (O − E)²/E, and total the last column. Degrees of freedom \( \nu = c - 1 \), where \( c \) is the number of classes — you are expected to know this formula, as it is not provided. Compare your value with the critical value at p = 0.05 for that number of degrees of freedom.

• χ² less than the critical value → the difference is not significant, is due to chance, and the null hypothesis is accepted.
• χ² greater than the critical value → the difference is significant, chance alone is an inadequate explanation, and the null hypothesis is rejected — so something else, such as linkage or differential mortality, is operating.

Chi-squared uses counts, never percentages or ratios, and questions will only ask it on one row or column of data.

Genes, proteins and phenotype

Four examples are named, and each should be learnt as gene → protein → phenotype:

• TYR → tyrosinase → albinism. A recessive allele codes for a non-functional tyrosinase, so the pathway converting tyrosine to melanin is blocked and no pigment is made.
• HBB → the β-globin of haemoglobin → sickle cell anaemia. A single base substitution changes one amino acid; the altered haemoglobin polymerises when oxygen is low, distorting red blood cells into a sickle shape. The alleles are codominant: heterozygotes have both normal and sickle haemoglobin, and have some resistance to malaria.
• F8 → factor VIII → haemophilia. An X-linked recessive allele gives non-functional factor VIII, so the blood clotting cascade fails.
• HTT → huntingtin → Huntington’s disease. A dominant allele with an expanded repeat produces an altered huntingtin protein that damages neurones; because onset is usually after reproductive age, the allele is not removed by selection.

Gibberellin and stem length. The dominant allele Le codes for a functional enzyme in the gibberellin synthesis pathway, so gibberellin is made and the stem elongates — tall plants. The recessive le codes for a non-functional enzyme, so little gibberellin is made and plants are dwarf. Applying gibberellin to a dwarf plant makes it grow tall, which is neat evidence that the gene acts through the hormone.

Gene control

Structural genes code for proteins used in the cell’s structure or metabolism; regulatory genes code for proteins that control the expression of other genes. An inducible enzyme is made only when its substrate is present; a repressible enzyme is made continuously until something switches it off.

The lac operon is the syllabus’s prokaryotic example. A regulatory gene codes for a repressor protein.

• Lactose absent: the repressor binds to the operator. RNA polymerase cannot bind at the promoter and move along, so the structural genes are not transcribed and no enzymes are made — no waste.
• Lactose present: lactose binds to the repressor and changes its shape, so it can no longer bind the operator. RNA polymerase now transcribes the structural genes, and the enzymes for taking up and hydrolysing lactose are made. They are therefore inducible enzymes.

Knowledge of the role of cAMP in the operon is not required.

In eukaryotes, transcription factors are proteins that bind to DNA and decrease or increase the rate of transcription of particular genes. The gibberellin example completes the story from Topic 15: gibberellin causes the breakdown of DELLA protein repressors, which normally inhibit the transcription factors that promote transcription. Removing the repressor releases the factors, so the amylase gene is switched on.