Principles of Inheritance and Variation

Written and reviewed by Anjali Sharma, Biology faculty at UniDrill (M.Sc. Botany, Banaras Hindu University · 8 years teaching NCERT Biology). Based on NCERT Biology Class XII, Chapter 4.

Two healthy parents, one sick child: how?

A couple who both have normal blood have a child with sickle cell anaemia. Nobody in the family did anything wrong, and nothing was "skipped". The answer is that the child received two copies of a recessive allele, one hidden in each parent. A monk growing peas in a monastery garden worked out the logic in the 1850s. Everything in this chapter, from blood groups to colour blindness to Down's syndrome, is that logic stretched to cover more situations.

Genetics is the study of inheritance (passing of characters from parent to progeny) and variation (the degree to which progeny differ from their parents).

The vocabulary you need first

Why Mendel succeeded with peas

Mendel crossed garden peas for seven years (1856 to 1863). He chose 14 true breeding lines, arranged as seven pairs of contrasting traits. The pea gave him easy control: it self pollinates naturally, so lines stay pure, and he could cross plants by removing anthers from a flower (emasculation), dusting it with pollen of another plant and covering it with a bag.

His real innovation was mathematical. He used large samples and applied statistics to biology for the first time, so a ratio like 3:1 could stand out from chance. Table below gives the seven pairs.

Notice what is not here: pink flowers, or leaf shape. Pink flowers are an intermediate, which Mendel's peas never produced.

The monohybrid cross: one trait at a time

Cross true breeding tall (TT) with true breeding dwarf (tt). Every F1 plant is Tt and looks tall. The dwarf trait has not vanished. When F1 plants self pollinate, F2 comes out as three tall plants for every one dwarf.

The Punnett square, devised by the British geneticist Reginald C. Punnett, lists the gametes of one parent along the top and the other down the side, so every possible offspring combination can be read from the boxes.

From the grid: phenotypic ratio 3 tall : 1 dwarf, genotypic ratio 1 TT : 2 Tt : 1 tt. These two ratios differ in complete dominance because TT and Tt look the same, so keep them apart.

Law of Dominance (Mendel's first law). Characters are controlled by discrete units called factors, which occur in pairs. In a dissimilar pair, one factor dominates the other. This explains why F1 is all tall.

Law of Segregation (second law). The two alleles of a pair do not blend. They separate during gamete formation, so each gamete carries only one allele. A heterozygote therefore makes two kinds of gametes in equal numbers, and this is why the dwarf trait reappears in F2.

Test cross. How do you tell whether a tall plant is TT or Tt? Cross it with the homozygous recessive (tt). If every offspring is tall, the plant is TT. If tall and dwarf appear in a 1:1 ratio, it is Tt.

Pause and predict: a tall pea plant is test crossed and gives 24 tall and 26 dwarf offspring. What is its genotype?

Check your answer: Tt. A TT plant would give only tall offspring. The near 1:1 ratio shows the unknown plant made two kinds of gametes in equal numbers.

Beyond the textbook. For the exam: the dominant allele hides the recessive one. In reality: dominance is not a fight between strong and weak alleles. A typical dominant allele codes for a working enzyme or protein, and the recessive allele often codes for a faulty or missing one. One working copy is usually enough, so the heterozygote looks normal. This is also why a "dominant" trait is not always the common one in a population.

When dominance is not complete

Mendel's peas gave tidy results, but many traits do not.

Incomplete dominance. In snapdragon (Antirrhinum), red (RR) crossed with white (rr) gives an F1 of Rr that is pink, a blend between the two parents. In F2 the ratio is 1 red : 2 pink : 1 white. Here the phenotypic and genotypic ratios are both 1:2:1, because the heterozygote is distinct.

Co-dominance. Both alleles show up fully and separately in the heterozygote. The classic example is the ABO blood group. The gene I has three alleles: IA, IB and i. IA makes sugar A on the surface of red blood cells, IB makes sugar B, and i makes no sugar. IA and IB are dominant over i, but they are co-dominant with each other, so IA IB produces both sugars, giving blood group AB.

Multiple alleles. ABO is also the example of a gene with more than two alleles in the population. Any one person carries only two of them, so six genotypes give four phenotypes.

Pause and predict: a woman with blood group A and a man with blood group B have a child with blood group O. Is that possible?

Check your answer: yes. The mother is IA i and the father is IB i. The child received an i from each of them and has genotype ii. Each parent hid a recessive allele, just like the sickle cell parents in the opening question.

One gene, two kinds of dominance. In pea starch synthesis, gene B has two alleles. BB seeds are round with large starch grains, bb seeds are wrinkled with small grains, and Bb seeds are round but have intermediate sized grains. So Bb shows complete dominance for shape and incomplete dominance for grain size. Dominance depends on which phenotype you examine.

The dihybrid cross: two traits together

Mendel crossed round yellow seeds (RRYY) with wrinkled green seeds (rryy). F1 is all round yellow (RrYy). When F1 self pollinates, the F2 phenotypes appear in the ratio 9 round yellow : 3 round green : 3 wrinkled yellow : 1 wrinkled green, taken from a 16 box Punnett square. There are 9 genotypes in the ratio 1:2:1:2:4:2:1:2:1.

Law of Independent Assortment. When two pairs of traits are combined in a hybrid, the segregation of one pair is independent of the other pair. RrYy therefore makes four gamete types, RY, Ry, rY and ry, each 25 percent.

The easy way to solve questions is to multiply separate probabilities. For TtYy crossed with Ttyy, dwarf needs tt (one in four from Tt × Tt), and green needs yy (one in two from Yy × yy). A dwarf green plant is 1/4 × 1/2 = 1/8.

One condition is hidden in the law: it works only for genes on different chromosomes (or very far apart on the same one). The next sections explain what happens when genes share a chromosome.

Chromosomes carry the genes

Mendel's work was published in the 1860s but went unrecognised until 1900. In 1902 Walter Sutton and Theodore Boveri noticed that chromosomes behave exactly like Mendel's factors, which led to the Chromosomal Theory of Inheritance.

Morgan's flies. Thomas Hunt Morgan tested the theory on the fruit fly Drosophila melanogaster, which is ideal: it grows on simple synthetic medium, completes its life cycle in about two weeks, produces many offspring from a single mating, has clearly distinguishable males and females, and shows many hereditary variations that are easy to see.

Linkage and recombination. Morgan found that when two genes lie on the same chromosome, the parental combinations appear more often than the new ones. He called their physical association linkage, and the generation of non-parental combinations recombination. The closer two genes are, the less often they are separated.

Alfred Sturtevant, a student of Morgan, used recombination frequency as a measure of the distance between genes and used it to map their positions on the chromosome. This was the first genetic mapping.

Pause and predict: gene pair A shows 2 percent recombination and gene pair B shows 30 percent. Which pair is closer together?

Check your answer: pair A. Low recombination means tight linkage, which means the genes sit close together on the chromosome. Students often invert this.

Polygenic inheritance and pleiotropy

Polygenic inheritance. Some traits are controlled by three or more genes, and the effect of each allele adds up. Human skin colour and height are the examples. With three genes, AABBCC is the darkest, aabbcc is the lightest, and AaBbCc is intermediate. The number of capital letters decides the shade. The environment also influences the phenotype, so these traits show a continuous range rather than distinct classes.

Pleiotropy is the reverse: one gene, many effects. In phenylketonuria, a mutation in the gene for the enzyme phenylalanine hydroxylase leads to mental retardation as well as reduced pigmentation of hair and skin.

Sex determination

Sex is decided by chromosomes in different ways in different animals. Henking (1891) first noticed a special nuclear structure, which he called the X body, that went to only half of the sperm in some insects. It was later identified as a chromosome.

In humans, each person has 22 pairs of autosomes and one pair of sex chromosomes. Every egg carries an X. Half of the sperm carry an X and half carry a Y, so the father's sperm decides the sex of the child. In birds, it is the opposite: the mother's egg decides, because the female makes two kinds of gametes (Z or W).

In honey bees, the queen and the workers (females) develop from fertilised eggs, so they are diploid. The drones (males) develop from unfertilised eggs by parthenogenesis, so they are haploid and make sperm by mitosis. A drone therefore has no father and cannot have sons, but has a grandfather and can have grandsons.

Mutation

A mutation is a change in the DNA sequence that changes the genotype and sometimes the phenotype. Deletions, insertions and duplications of DNA segments are chromosomal aberrations, and are common in cancer cells. A change in a single base pair is a point mutation, and sickle cell anaemia is the standard example. Agents that cause mutations are mutagens, and UV radiation is one.

Pedigree analysis

Humans cannot be crossed on demand, so geneticists study a trait across generations in a family tree. Learn the symbols below.

Mendelian disorders

A Mendelian disorder is caused by a mutation in a single gene and follows Mendel's rules. Whether it is dominant or recessive, and autosomal or X linked, decides the pattern in a pedigree.

Why X linked disorders strike males more. A female has two X chromosomes, so a recessive allele on one is usually covered by a normal allele on the other. A male has one X and a Y, so any recessive allele on his X shows. A son always gets his X from his mother and his Y from his father, so a son can never inherit an X linked trait from his father. A father passes his X to every daughter.

For an unaffected carrier mother and a normal father, half of the sons are affected and half of the daughters are carriers. A woman would have to be homozygous for the recessive allele to be haemophilic, which requires a carrier mother and a haemophilic father. Haemophilic females are extremely rare. Queen Victoria was a carrier, and her pedigree shows haemophilia spreading through the royal families of Europe.

Pause and predict: a colour blind man marries a woman who is not a carrier. What are the colour vision outcomes for their sons and daughters?

Check your answer: all sons are normal, because they get his Y and her normal X. All daughters are carriers, because they get his affected X and her normal X. None of the children is colour blind, but every daughter is a carrier.

Sickle cell anaemia. The alleles are HbA and HbS. Only HbS HbS individuals have the disease, and HbA HbS people are carriers. The mutation is a single base substitution in the gene for the beta globin chain: the sixth codon changes from GAG to GUG (written as mRNA), replacing glutamic acid with valine. Valine is not charged, so the mutant haemoglobin clumps when oxygen is low and bends the biconcave red cell into a sickle shape. If both parents are carriers (HbA HbS × HbA HbS), each child has a 1 in 4 chance of the disease. That is the answer to the question at the start.

Beyond the textbook. For the exam: HbA HbS carriers are normal and HbS HbS is diseased. In reality: carriers are partly protected against malaria. In regions where malaria has been common, this protection has kept the harmful allele frequent in the population, which is a well known case of an advantage in the heterozygote.

Phenylketonuria. The affected child lacks the enzyme that converts the amino acid phenylalanine into tyrosine. Phenylalanine and its by products, such as phenylpyruvic acid, build up and reach the brain, where they cause mental retardation, and part is excreted in the urine.

Thalassaemia versus sickle cell. Sickle cell is a qualitative defect: a globin chain is made, but it is the wrong one. Thalassaemia is a quantitative defect: too little globin is made. Alpha thalassaemia is controlled by two closely linked genes, HBA1 and HBA2, on chromosome 16, and beta thalassaemia by a single gene, HBB, on chromosome 11.

Chromosomal disorders

These arise from the absence, excess or abnormal arrangement of chromosomes, not from a single gene mutation. Aneuploidy is the gain or loss of a chromosome, caused by the failure of chromosomes to separate (segregate) during cell division. Polyploidy is the gain of an entire extra set of chromosomes, caused by failure of cytokinesis after chromosome replication, and it is seen mainly in plants. An extra chromosome is a trisomy (2n + 1) and a missing one is a monosomy (2n − 1).

Down's syndrome was first described by Langdon Down in 1866.

Beyond the textbook. For the exam: aneuploidy comes from failed chromosome separation. In reality: the risk of Down's syndrome rises with the age of the mother, because the failure to separate happens mostly in the egg during meiosis. Down's, Klinefelter's and Turner's are all aneuploidies, while haemophilia and thalassaemia are single gene disorders, not chromosomal ones.

Exam traps

60-second revision

Where this chapter connects

• Previous: Reproductive Health covers the reproductive side of humans. Here you follow the genes that those gametes carry.
• Next: Molecular Basis of Inheritance opens up what Mendel's factors really are: DNA, and how it is copied, transcribed and translated.
• Class XI link: Cell Cycle and Cell Division explains meiosis, whose chromosome movements are the physical basis of segregation and independent assortment.