Principles of Inheritance and Variation: NEET notes

1. Mendel's laws of inheritance

NCERT § "Mendel's Laws of Inheritance"

• Inheritance is the transfer of characters from parents to progeny and is what heredity rests on; variation is how far the progeny differ from their parents.
• Gregor Mendel ran hybridisation experiments on garden pea for seven years, from 1856 to 1863, and proposed the laws of inheritance from them.
• His pea work marked the first use of statistical analysis and mathematical logic on a problem in biology, and his large sample sizes made his data more credible.
• He began with 14 true-breeding pea varieties that formed pairs differing in one character with two contrasting forms. A true-breeding line keeps showing the same trait after many generations of self-pollination.
• The seven characters and their dominant form: stem height (tall), flower colour (violet), flower position (axial), pod shape (inflated), pod colour (green), seed shape (round), seed colour (yellow). The recessive forms are dwarf, white, terminal, constricted, yellow pod, wrinkled seed and green seed.

2. Inheritance of one gene: dominance and segregation

NCERT § "Inheritance of One Gene"

• In a monohybrid cross of tall with dwarf pea, all F₁ plants were tall. Self-pollinating F₁ gave F₂ plants in a 3 tall : 1 dwarf ratio, and the dwarf plants were as dwarf as the original parent, with no blending.
• Mendel said a stable 'factor' passes each character from parent to offspring; these factors are now called genes. Alternative forms of one gene are alleles, such as T and t.
• A plant with two identical alleles (TT or tt) is homozygous; one with two different alleles (Tt) is heterozygous. Tt is a hybrid that looks tall, so genotype and phenotype are not the same thing.
• The F₂ genotypic ratio is 1 TT : 2 Tt : 1 tt, while the phenotypic ratio is 3 tall : 1 dwarf. The Punnett square, drawn by Reginald C. Punnett, is used to work these out.
• A test cross crosses an organism of unknown genotype showing the dominant trait with the recessive parent. A 1:1 result shows it was heterozygous; all-dominant offspring show it was homozygous.
• Law of dominance: characters are controlled by paired factors, and in a dissimilar pair one factor is expressed (dominant) while the other is masked (recessive). It explains why only one parental form shows in F₁ and both show in F₂.
• Law of segregation: the two alleles of a pair do not blend; they separate during gamete formation so each gamete gets only one of them. A homozygote makes one kind of gamete, a heterozygote two kinds in equal numbers.

3. Incomplete dominance, co-dominance and multiple alleles

NCERT § "Inheritance of One Gene"

• In incomplete dominance the heterozygote looks intermediate. In the dog flower (snapdragon, Antirrhinum sp.), red (RR) × white (rr) gives pink F₁ (Rr), and selfing F₁ gives F₂ of 1 red : 2 pink : 1 white.
• In incomplete dominance the phenotypic and genotypic F₂ ratios become the same (1:2:1), because every genotype has its own look.
• Dominance can be explained at the level of gene products: a normal allele usually makes a working enzyme, while a modified allele may make a normal enzyme, a less efficient one, a non-functional one, or none. Where the modified allele gives no working product, it behaves as recessive.
• Dominance is not an absolute property of an allele; it depends on the gene product and on which phenotype we choose to look at. In pea seeds, one gene controls starch synthesis: BB seeds have large starch grains and are round, bb seeds have smaller grains and are wrinkled, and Bb seeds are round but with intermediate grain size. Judged by seed shape, B is dominant; judged by grain size, the alleles show incomplete dominance.
• In co-dominance the F₁ shows both parental characters fully. Human ABO blood groups are the NCERT example.
• The ABO gene I has three alleles, Iᴬ, Iᴮ and i. Iᴬ and Iᴮ make slightly different forms of the sugar polymer on the red blood cell surface, while i makes none. Iᴬ and Iᴮ are fully dominant over i but co-dominant with each other.
• With three alleles there are six genotypes and four blood groups: A (IᴬIᴬ, Iᴬi), B (IᴮIᴮ, Iᴮi), AB (IᴬIᴮ) and O (ii).
• ABO is also an example of multiple alleles, where more than two alleles govern one character. Since one person carries only two alleles, multiple alleles can be detected only by studying a population.

4. Inheritance of two genes: independent assortment

NCERT § "Inheritance of Two Genes"

• In a dihybrid cross Mendel crossed round-yellow (RRYY) with wrinkled-green (rryy) peas. All F₁ seeds were round and yellow (RrYy).
• Selfing the F₁ produced an F₂ ratio of 9 round yellow : 3 round green : 3 wrinkled yellow : 1 wrinkled green, from 16 combinations of gametes.
• Looked at one character at a time, round : wrinkled and yellow : green are each 3:1, showing that each gene still segregates on its own.
• Law of independent assortment: if a hybrid carries two pairs of traits together, one pair segregates independently of the other. So an RrYy plant produces four kinds of gametes, RY, Ry, rY and ry, in equal proportion.
• A dihybrid test cross (RrYy × rryy) gives four phenotypes in a 1:1:1:1 ratio.
• Mendel's work, published in 1865, went unrecognised for years, partly because factors were abstract, not physically observed, and his mathematical approach was new to biologists. It was rediscovered independently in 1900 by de Vries, Correns and von Tschermak.

5. Chromosomal theory, linkage and recombination

NCERT § "Inheritance of Two Genes"

• Better microscopes let scientists follow chromosome behaviour in division. Chromosomes, like Mendel's factors, occur in pairs, separate at gamete formation and assort independently.
• Walter Sutton and Theodore Boveri noticed that chromosome movement in meiosis parallels the behaviour of Mendel's factors. Sutton combined chromosomal segregation with Mendel's principles into the chromosomal theory of inheritance.
• Thomas Hunt Morgan and colleagues tested this experimentally with the fruit fly Drosophila melanogaster, which grows on a simple synthetic medium, finishes its life cycle in about two weeks, gives many progeny from one mating, has easily distinguishable males and females and shows many heritable variations visible under a low-power microscope.
• Morgan crossed flies differing in X-linked genes. In the F₂, the parental gene combinations appeared much more often than the new (non-parental) ones, so these genes did not assort independently.
• Morgan explained this with linkage, the physical association of genes on one chromosome, and used recombination for the production of non-parental gene combinations.
• Tightly linked genes show little recombination, while loosely linked genes show more. In Morgan's data, yellow body and white eye genes gave 1.3 per cent recombination, whereas white eye and miniature wing genes gave 37.2 per cent.
• Morgan's student Alfred Sturtevant took the recombination frequency between two genes on one chromosome as a measure of how far apart they are, and used it to map gene positions. Genetic maps of this kind now serve as a starting point for sequencing whole genomes.

6. Polygenic inheritance and pleiotropy

NCERT § "Polygenic Inheritance" and § "Pleiotropy"

• Mendel's traits fall into distinct classes, but many traits, like human height or skin colour, vary continuously across a range. Usually three or more genes control such traits, which are called polygenic traits.
• In polygenic inheritance each allele contributes a small additive effect, and the environment also influences the outcome.
• In the NCERT model of human skin colour, three genes A, B and C control it, with dominant alleles adding dark pigment. AABBCC is darkest, aabbcc is lightest, and AaBbCc is intermediate.
• Pleiotropy is when one gene produces more than one phenotypic effect. The usual basis is that the gene affects a metabolic pathway feeding several phenotypes.
• Phenylketonuria is the NCERT example of pleiotropy: a mutation in the gene for phenylalanine hydroxylase leads to mental retardation as well as reduced hair and skin pigmentation.

7. Sex determination

NCERT § "Sex Determination"

• In 1891 Henking, studying spermatogenesis in some insects, saw that half the sperms received a particular nuclear structure and half did not. He called it the X body; it was later recognised as a chromosome and named the X chromosome.
• XO type: in many insects such as grasshoppers, males have one X besides the autosomes while females have two X. Males therefore make two kinds of sperm, with and without X.
• XY type: in many insects and in mammals including humans (and Drosophila), males have one X and one smaller Y, while females are XX.
• Chromosomes that decide sex are sex chromosomes; the rest are autosomes. In both XO and XY systems the male produces two kinds of gametes, so these are examples of male heterogamety.
• In birds, female heterogamety is seen: females are ZW and produce two kinds of eggs, while males are ZZ and homogametic.
• Humans have 23 pairs of chromosomes, 22 pairs of autosomes and one pair of sex chromosomes. Females make only X-bearing ova; males make X-bearing and Y-bearing sperms in equal proportion.
• Because the sperm type decides the zygote's sex, there is an equal (50 per cent) chance of a boy or a girl in each pregnancy, and the father's gamete determines it.
• Honey bees use a haplodiploid system based on the number of chromosome sets. A fertilised egg develops into a female (queen or worker) with 32 chromosomes (diploid), while an unfertilised egg develops by parthenogenesis into a male (drone) with 16 chromosomes (haploid).
• Since drones are haploid, they make sperms by mitosis. A drone has no father and so cannot have sons, but it does have a grandfather and can have grandsons.

8. Mutation

NCERT § "Mutation"

• Mutation is a change in the DNA sequence, which changes the genotype and phenotype of an organism. Along with recombination, it is a source of variation.
• Loss (deletion) or gain (insertion or duplication) of a DNA segment changes chromosomes. Such chromosomal aberrations are commonly seen in cancer cells.
• Sickle-cell anaemia is the classic example of a point mutation, where only one base pair of DNA is changed.
• Deletion or insertion of base pairs can cause frame-shift mutations.
• Chemical and physical agents that cause mutation are mutagens; UV radiation is one of them.

9. Genetic disorders: pedigree and Mendelian disorders

NCERT § "Genetic Disorders"

• Controlled crosses are impossible in humans, so inheritance of a trait is traced through a family tree over several generations; this is pedigree analysis, and it helps in genetic counselling.
• Mendelian disorders are caused by a change in one gene and are inherited according to Mendel's rules. They can be autosomal or sex-linked, dominant or recessive; examples are colour blindness, haemophilia, sickle-cell anaemia, cystic fibrosis, thalassemia and phenylketonuria.
• Haemophilia is sex-linked recessive: one protein of the clotting cascade is affected, so a small cut may bleed without stopping. A heterozygous (carrier) female can pass it to sons. An affected female is very rare, as her mother must be at least a carrier and her father haemophilic. Queen Victoria's family had many haemophilic descendants because she was a carrier.
• Colour blindness, a sex-linked recessive disorder, results from a defect in the red or green cone cells of the eye. About 8 per cent of males have it, whereas among females the figure is only about 0.4 per cent, since a female is affected only if both her X chromosomes carry the allele.
• Sickle-cell anaemia is autosomal recessive. Only HbˢHbˢ individuals show the disease; HbᴬHbˢ heterozygotes are unaffected carriers who can pass it on.
• It is caused by a single base change in the codon, GAG → GUG, which puts valine (Val) in place of glutamic acid (Glu) at position six of the beta-globin chain. At low oxygen tension the altered haemoglobin polymerises, and the red cells become elongated and sickle-shaped.
• Phenylketonuria is an autosomal recessive inborn error of metabolism. The affected person lacks the enzyme that converts phenylalanine to tyrosine, so phenylalanine builds up and is converted to phenylpyruvic acid and related compounds; their build-up in the brain causes mental retardation, and poor kidney absorption leads to their excretion in urine.
• Thalassemia, an autosomal recessive blood disease, results from a mutation or deletion that lowers the synthesis of one of the globin chains, leading to abnormal haemoglobin and anaemia. In α-thalassemia the genes involved are HBA1 and HBA2, a closely linked pair on chromosome 16; β-thalassemia involves one gene, HBB, on chromosome 11.
• Thalassemia is a quantitative problem (too few globin molecules are made), whereas sickle-cell anaemia is a qualitative problem (a globin that works incorrectly is made).

10. Chromosomal disorders

NCERT § "Genetic Disorders"

• Chromosomal disorders result when one or more chromosomes are absent, in excess, or abnormally arranged.
• Aneuploidy is a gain or loss of chromosomes caused by failure of chromatid segregation during cell division. Polyploidy is an increase in whole chromosome sets caused by failure of cytokinesis after telophase, and is often seen in plants.
• Trisomy means an extra copy of one chromosome; monosomy means one chromosome is missing.
• Down's syndrome is trisomy of chromosome 21, first described by Langdon Down in 1866. Affected people are short with a small round head, furrowed tongue and partly open mouth, have a broad palm with a characteristic crease, and show delayed physical, psychomotor and mental development.
• Klinefelter's syndrome has an extra X in a male, giving 47, XXY. The person has an overall masculine build but also some feminine features such as breast development (gynaecomastia), and is sterile.
• Turner's syndrome is the absence of one X in a female, giving 45, X0. These females are sterile, with rudimentary ovaries and a lack of other secondary sexual characters.

Must-know facts

1. Mendel worked on garden pea from 1856 to 1863 using 14 true-breeding varieties and 7 pairs of contrasting characters.
2. Green pod colour and yellow seed colour are dominant in pea; axial flower position and inflated pod are also dominant.
3. Monohybrid F₂: phenotype 3:1, genotype 1:2:1. Dihybrid F₂: phenotype 9:3:3:1 out of 16.
4. Monohybrid test cross of a heterozygote gives 1:1; dihybrid test cross gives 1:1:1:1.
5. Snapdragon (Antirrhinum sp.) shows incomplete dominance: F₂ is 1 red : 2 pink : 1 white, so phenotypic and genotypic ratios match.
6. ABO: three alleles, six genotypes, four phenotypes; Iᴬ and Iᴮ co-dominant, both dominant over i.
7. Pea starch grain size (gene B) shows incomplete dominance even though seed shape shows complete dominance.
8. Mendel's work was rediscovered in 1900 by de Vries, Correns and von Tschermak.
9. Sutton and Boveri matched chromosome behaviour to Mendel's factors, Sutton named it the chromosomal theory of inheritance, and Morgan verified it experimentally in Drosophila melanogaster.
10. Morgan's recombination: yellow body–white eye 1.3%; white eye–miniature wing 37.2%.
11. Sturtevant used recombination frequency to build genetic maps.
12. Human skin colour is the NCERT example of polygenic inheritance (three genes); phenylketonuria is the example of pleiotropy.
13. Henking (1891) named the X body; grasshopper is XO; humans and Drosophila are XY; birds are ZW with heterogametic females.
14. Honey bee: haplodiploid; females (queen, worker) are diploid with 32 chromosomes, drones are haploid with 16 and arise from unfertilised eggs by parthenogenesis.
15. Sickle-cell: Glu → Val at position 6 of beta-globin, GAG → GUG; autosomal recessive.
16. Haemophilia and colour blindness are X-linked recessive; colour blindness affects about 8% of males and about 0.4% of females.
17. α-thalassemia: HBA1 and HBA2 on chromosome 16; β-thalassemia: HBB on chromosome 11.
18. Down's syndrome = trisomy 21; Klinefelter's = 47, XXY; Turner's = 45, X0.
19. Aneuploidy comes from failed chromatid segregation; polyploidy from failed cytokinesis after telophase.

Common traps

Key terms

Allele

One of the alternative forms of a gene, such as T and t for pea height.

True-breeding line

A line that shows the same form of a trait over many generations of self-pollination.

Homozygous

Having two identical alleles of a gene.

Heterozygous

Having two different alleles of a gene.

Test cross

Crossing a dominant-looking individual with the recessive parent to reveal its genotype.

Incomplete dominance

Heterozygote shows a phenotype in between the two homozygotes.

Co-dominance

Both alleles are fully and separately expressed in the heterozygote.

Multiple alleles

More than two alleles of one gene existing in a population.

Linkage

Physical association of genes on the same chromosome, so they tend to be inherited together.

Recombination

Production of gene combinations not present in either parent.

Polygenic trait

A trait controlled by three or more genes whose effects add up.

Pleiotropy

One gene influencing more than one phenotypic trait.

Male heterogamety

The male produces two kinds of gametes with respect to sex chromosomes (XO or XY).

Female heterogamety

The female produces two kinds of gametes (ZW females in birds).

Point mutation

A change affecting only one base pair of DNA.

Pedigree analysis

Tracing a trait through a family tree over generations.

Aneuploidy

Gain or loss of individual chromosomes after failed chromatid segregation.

Polyploidy

Presence of extra complete chromosome sets after failed cytokinesis.