7.2 Genetics, Heredity, and Molecular Biology

7.2 Genetics, Heredity, and Molecular Biology

Genetics items at senior-high level are almost always solvable on paper inside a minute, provided you can translate a word problem into symbols and then draw the right grid. This section assumes you already know where the nucleus and ribosomes sit, which is covered in 7.1, and concentrates instead on what the DNA inside them does across generations.

1. Mendel's two laws and the vocabulary that carries them

Gregor Mendel's pea experiments produced two rules that still frame every cross:

• Law of segregation — the two alleles of a gene separate during gamete formation, so each sperm or egg carries only one of them.
• Law of independent assortment — alleles of different genes are handed to gametes independently, provided the genes sit on different chromosomes.

A dominant allele is not the common one. Polydactyly is dominant and rare, while the recessive allele behind blood type O is extremely common. Frequency and dominance are unrelated ideas.

Monohybrid crosses and the test cross

Cross two heterozygous tall plants, Tt × Tt:

Genotypic ratio 1 TT : 2 Tt : 1 tt; phenotypic ratio 3 tall : 1 short. Items very often ask for one and supply the other as bait.

A test cross answers a different question. A tall plant may be TT or Tt and you cannot tell by looking, so you cross it with the homozygous recessive tt:

• If the unknown parent is TT, every offspring is Tt and therefore 100% tall.
• If the unknown parent is Tt, half the offspring are Tt and half are tt, giving 1 tall : 1 short.

A single short offspring is enough to prove the unknown parent was heterozygous.

Worked example 1 — a dihybrid cross without drawing sixteen boxes

In peas, round seed R is dominant to wrinkled r, and yellow Y is dominant to green y. Cross RrYy × RrYy and predict 320 seeds.

1. Treat each gene on its own. Rr × Rr gives three-quarters round and one-quarter wrinkled; Yy × Yy gives three-quarters yellow and one-quarter green.
2. Multiply the separate probabilities (the product rule):
   • round and yellow = 3/4 × 3/4 = 9/16
   • round and green = 3/4 × 1/4 = 3/16
   • wrinkled and yellow = 1/4 × 3/4 = 3/16
   • wrinkled and green = 1/4 × 1/4 = 1/16
3. That is the classic 9 : 3 : 3 : 1 phenotypic ratio.
4. With 320 seeds, one-sixteenth is 320 ÷ 16 = 20. Expect 180 round-yellow, 60 round-green, 60 wrinkled-yellow and 20 wrinkled-green.

2. When Mendel's ratios do not appear

ABO blood typing

The A and B alleles are codominant with each other and both are dominant over the O allele, written as a lowercase i.

Worked example 2 — can these parents have that child?

A man with type A blood and a woman with type B blood present a child with type O. Is that genetically possible?

1. Type O is $ii$, so the child received an O allele from each parent.
2. The father must therefore be $I^A i$, not $I^A I^A$.
3. The mother must likewise be $I^B i$.
4. Crossing $I^A i$ × $I^B i$ gives $I^A I^B$ (AB), $I^A i$ (A), $I^B i$ (B) and $ii$ (O), each with probability one-quarter.

So yes — and more strikingly, two parents of types A and B can produce children of all four blood types.

Sex-linked traits

Males are XY. A gene on the X has no partner on the much smaller Y, so a male is hemizygous and one recessive allele is enough to express the trait. Females are XX and need two copies. Writing $X^C$ for normal vision and $X^c$ for colour blindness, take a carrier mother $X^C X^c$ and a father with normal vision $X^C Y$:

Half the sons are affected, no daughter is affected, half the daughters are carriers, and one quarter of all the children are colour blind — all of them boys. Note too that a father never passes an X-linked allele to a son, because what he gives a son is the Y.

3. Reading a pedigree

Squares are males and circles are females; a shaded symbol means affected; a horizontal line joins mates and a vertical line drops to their children; generations carry Roman numerals. Three diagnostic patterns cover almost every item:

• Autosomal recessive — two unaffected parents produce an affected child, the trait appears to skip generations, and both sexes are affected roughly equally.
• Autosomal dominant — every affected child has at least one affected parent, so the trait shows in every generation.
• X-linked recessive — affected individuals are overwhelmingly male, and the trait travels from an affected grandfather through an unaffected carrier daughter to a grandson.

4. DNA, RNA and the central dogma

A nucleotide is a phosphate group plus a five-carbon sugar plus a nitrogenous base. In DNA (deoxyribonucleic acid) the sugar is deoxyribose, and two antiparallel strands twist into a double helix held together by hydrogen bonds between complementary bases: A pairs with T using two bonds, G pairs with C using three.

Chargaff's rule follows directly — %A = %T and %G = %C. If a sample is 30% adenine, thymine is also 30%, and the remaining 40% splits evenly into 20% guanine and 20% cytosine.

Replication is semiconservative: helicase unzips the helix, DNA polymerase lays complementary nucleotides along each exposed strand, and each new double helix keeps one old strand paired with one new one.

Transcription copies one DNA strand into messenger RNA (mRNA) using RNA polymerase, substituting uracil wherever thymine would have gone. Translation then happens on a ribosome: mRNA is read three bases at a time as a codon, and each codon is matched by the anticodon of a transfer RNA (tRNA) carrying one amino acid. AUG is the start codon and codes for methionine; UAA, UAG and UGA are stop codons and code for no amino acid at all. There are 64 codons for only 20 amino acids, so the code is degenerate — several codons can specify the same amino acid.

A short worked reading: the template DNA 3'-TAC GGA TTT ACG ATC-5' transcribes to mRNA 5'-AUG CCU AAA UGC UAG-3', which translates to methionine, proline, lysine, cysteine and then stops — a peptide of four amino acids.

5. Mutations, chromosomes and karyotypes

A mutation is any change in the base sequence.

• A point or substitution mutation swaps a single base. It may be silent because the code is degenerate, missense when one amino acid changes — sickle-cell anaemia comes from one GAG to GTG change that puts valine where glutamic acid belongs — or nonsense when a stop codon appears early and truncates the protein.
• A frameshift mutation inserts or deletes bases in a number not divisible by three. Every codon after the change is read in the wrong grouping, so frameshifts are usually far more destructive than substitutions.
• Mutations in body cells affect only that individual. Only mutations arising in gametes are inherited.

A human body cell carries 46 chromosomes in 23 pairs: 22 pairs of autosomes and one pair of sex chromosomes, XX in females and XY in males. A gamete carries 23. A karyotype is a photograph of those chromosomes sorted by size, and it is how doctors detect nondisjunction, the failure of chromosomes to separate during meiosis.

Common traps

• Giving the genotypic ratio 1:2:1 when the item asked for the phenotypic ratio 3:1.
• Treating a test cross as a cross between two heterozygotes. A test cross is always against the homozygous recessive.
• Confusing incomplete dominance with codominance. Pink snapdragons are a blend; an AB red cell shows both antigens intact and unblended.
• Assuming an affected father passes an X-linked allele to his sons. He passes it to every daughter and to no son.
• Writing that Down syndrome involves 45 chromosomes. A trisomy adds one, giving 47.
• Applying Chargaff's rule to RNA. It holds only for double-stranded DNA.