Principles of Inheritance and Variation-Notes

1 Mendelian GeneticsGregor Johann Mendel (Father of Genetics) Many experiments were done by Mendel on the garden pea plant (Pisum sativum) between 1856 and 1863. He studied the results of the experiments and deduced many observations. Thus, Mendel’s laws of inheritance came into existence. 

Mendel’s Experiments on Pea Plant

Mendel selected the pea plant for his experiments due to many reasons. These are:

1. The flowers of this plant are bisexual.
2. They are naturally self-pollinating, but self and cross-pollination can easily be performed.
3. It had few distinguishable external features.
4. They have a shorter life span and the plants are easier to maintain.

Mendel made a list of characters with contrasting traits found in pea plants.

Monohybrid cross

• In the landmark experiment ofGregor Mendel, monohybrid crosses helped in determining the dominant and recessive traits in pea plants.
• He cross-pollinated two pure lines for contrasting characters and the resultant offspring were called F1 generation (first filial generation).

• The F1 generation offspring were then self-pollinated to give the F2 generation or the second filial generation.
• A cross between a pure yellow seed pea plant with a pure green seed pea plant is a monohybrid cross.

• The following conclusions were drawn from Mendel’s monohybrid crosses.

1. The genes that are passed from the parents to the offspring exist in pairs. These pairs are called alleles.
2. When the two alleles are the same, they are called homozygous. When both alleles are different, they are called heterozygous.
3. Dominant characters are described using capital letters and recessive using small letters. For example, the dominant genes for tallness in a pea plant are written as TT and recessive genes as tt.
4. The heterozygous genes are written as Tt where the plant appears tall and has the recessive gene which might express itself in future generations.
5. The physical appearance of the plant is known as the phenotype whereas the genetic makeup of the plant is called the genotype. So, a heterozygous plant has genotype Tt and it appears tall phenotypically.
6. During gametogenesis, when the chromosomes become half in the gametes, there is a 50% chance of either of the alleles to fuse with that of the other parent to form a zygote.

Laws of Inheritance Mendel proposed three laws of inheritance:

• Law of Dominance: According to this law, in a heterozygous condition, the allele whose characters are expressed over the other allele is called the dominant allele and the characters expressed by this dominant allele are called dominant characters. The characters appearing in the F1 generation are called dominant characters. The recessive characters appear in the F2 generation.
• Law of Segregation: Each individual possesses two alleles of a gene and each allele separates or segregates at the time of meiosis, that is, during the formation of gametes. The monohybrid cross (cross of a single trait) was used to explain the law of segregation of genes.

• Law of Independent Assortment: According to the law of independent assortment, there are separate genes for separate traits and characters and they influence and sort themselves independently of the other genes. The two genes segregate independently of each other as well as of other traits at the time of gametogenesis.

Analysis of Mendel’s ResultsBack cross It is a cross between (F1) hybrid with any one of its parents, to achieve offspring with a genetic identity closer to the parents. It is used to test inheritance theory. Test Cross A cross between (F1) hybrid and its homozygous recessive parent is known as Test Cross. it used to know whether the dominant trait is homozygous or heterozygous.

2 Exceptions to Mendel’s Laws Incomplete Dominance The inheritance pattern in which the first generation (F1) phenotype does not resemble either of the two parents but shows an intermediate character is called incomplete dominance. Example: In a Snapdragon (Antirrhinum majus) plant, when two types of pure breeding plants, one with red-flowers and the other with white-flowers are crossed, the F1 plants possess pink flowers. On selfing the plants with pink flowers, F2 generation so obtained has 1 red: 2 pink: 1 white flowered plants. The pink flower is due to incomplete dominance expressed by the genes for red flower colour and genes for white flower colour.

Codominance It is the phenomenon of two alleles lacking a dominance-recessive relationship and both expressing themselves equally in the organism. Example: ABO blood grouping systems in humans are controlled by gene I. The gene has three alleles I^A, I^B and i/I^O. Here I^A and I^B alleles are codominant and both these are dominant over i/I^O. Presence of these alleles decides the blood group in human beings.

Differences between Incomplete-dominance and codominance

Incomplete Dominance	Codominance
Alleles produce a mixture of the expression of two alleles.	There is no mixing of the effect of the two alleles.
The F1 does not resemble either of the parents.	The F1 resembles both the parents.
E.g.: Flower colour in Snapdragon plants	E.g.: ABO blood grouping system in humans

Multiple Allelism Multiple allelism is a deviation from the Mendelian inheritance pattern. It involves more than two alleles that code for a certain characteristic in a species. It involves the presence of more than two contrasting alleles for a gene. Example:ABO blood groups are the best examples for multiple allelism in human beings. The ABO blood group system was proposed by Karl Landsteiner. The blood groups A, B, AB and O are distinguished by the presence or absence of antigens on the surface of RBC. Persons with blood type A have antigen A on their RBCs and anti B antibodies in the plasma. Persons with blood type B have antigen B on their RBCs and anti A antibodies in the plasma. Persons with blood type AB have antigen A and B on the RBCs and no antibodies in the plasma. Persons with blood type O have no antigens on their RBCs and both anti-A and anti-B antibodies are present in the plasma. Bernstein discovered that the different phenotypes were inherited by the interactions of three autosomal alleles of the genes named ‘I’ located on chromosome 9. I^A, I^B and I^O are the three alleles of the gene. The alleles I^A and I^B are responsible for the production of the respective antigen A and B. The alleles I^O does not produce any antigen. The alleles I^A and I^B are dominant to the allele I^O, but co-dominant to each other. Phenotype and Genotypes of the alleles – I^A, I^B and I^O A child receives one of the three alleles from each parent, giving rise to six possible genotypes and four possible blood types. The genotypes are, I^AI^A, I^AI^O, I^BI^B, I^BI^O, I^AI^B, I^OI^O. The phenotypic expression of I^AI^A, I^AI^O is blood type A. The phenotypic expression of I^BI^B, I^BI^Ois blood type B. The phenotypic expression of I^AI^Bis blood type AB. The phenotypic expression of I^OI^Ois blood type O.

3 Chromosomal Theory of Inheritance and Morgan’s Experiments

Chromosome Theory of Inheritance

• Sutton and Boveri independently proposed the Chromosomal theory of inheritance in the year of 1902.
• This theory was proved by Thomas Hunt Morgan, who studied fruit flies (Drosophila melanogaster).
• According to Chromosomal theory of inheritance, the chromosome is the genetic material responsible for Mendelian inheritance. Mendel knew nothing of the chromosomes and meiosis.
• This theory states that individual genes are found at specific locations on particular chromosomes, and that the behaviour of chromosomes during meiosis can explain why genes are inherited according to Mendel’s laws.
• Thus, the similarity between the Mendelian factors and chromosomes became apparent.

How does the Chromosomal Theory of Inheritance support Mendel’s law?

• In somatic cells, the chromosome or gene occurs in homologous pairs as one chromosome is from the father and the other from the mother.

• During meiosis or gametogenesis, homologous chromosome pairs segregate independently of other chromosome pairs. Thus, a gamete contains only one particular type of chromosome i.e. a gamete contains only one of two alleles of a particular trait.

• The sorting of chromosomes from each homologous pair into pre-gametes appears to be random and it is similar to Mendel’s law of independent assortment.
• Similarly, chromosome is transferred from one generation to another. And the number of chromosomes are fixed in each organism.
• Even though male and female gametes differ in size and morphology, they have the same number of chromosomes, suggesting equal genetic contributions from each parent.
• The gametes combine during fertilization to produce offspring with the same number of chromosome as their parents.

Morgan’s Experiments on Drosophila melanogaster to explain Chromosomal Theory of Inheritance. In 1910, Thomas Hunt Morgan performed an experiment on Drosophila melanogaster (fruit fly).

• In the experiment, normal flies with red eyes and mutated flies with white eyes are crossed and offspring are observed.
• Dominant allele: red eye colour.
• Recessive allele (mutated): white eye colour.
• When a red eyed female (Xw+ Xw+) and white eyed male (Xw Y) were mated, all the progeny in the F1 generation had red eyes.
• In the next step he performed a reciprocal cross where a red eyed male (Xw+ Y) and white eyed female (Xw Xw) were crossed.
• A surprising result was obtained, in F1 generation instead of obtaining all the progeny with red eyes, the result showed that all the female progeny had red eyes and all the male progeny had white eyes.
• This result showed that traits for gender and eye color are linked, which is not in accordance to Mendel’s law of independent assortment.
• This result can be explained only if the gene for colour of eye is present on the X chromosome and is linked.

Thus, this experiment on eye colour of Drosophila supports the chromosome theory of inheritance.

4 Non-disjunction as Proof of the Chromosomal Theory of Inheritance Bridges’s Experiment

• Morgan showed that a gene for eye colour was on the X chromosome of Drosophila.
• One of his students, C. B. Bridges, secured proof of the chromosome theory by showing that exceptions to the rules of inheritance could also be explained by chromosome behaviour.
• Bridges performed one of Morgan’s experiments.
• In his experiment, awhite-eyed female Drosophila (Xw Xw) was crossed with red-eyed males (Xw+ Y).
• In F1 generation, the following results were obtained:
  • Almost all of the F1 progeny flies were either red-eyed females or white-eyed males which was normal.
  • But few flies such as white-eyed females and red-eyed males were also obtained which was exceptional.
• When he tried to cross red-eyed F1 progeny males with normal white-eyed females, it was found that all the F1 progeny red-eyed males were sterile.
• However, the F1 progeny white-eyed females were fertile. When these white-eyed females were crossed with normal red-eyed males, many F2 progeny were obtained as white-eyed females and red-eyed males.

It seems, the exceptional F1 progeny females produced a large number of exceptional progeny in a successive generation.

• Bridges explained these results by proposing that the exceptional F1 flies were the result of abnormal X chromosome behaviour during meiosis in the females of the P generation.
• Normally the X chromosome in females separates or disjoin during gametogenesis but occasionally, they might fail to separate, producing an egg with two X chromosomes (diplo-X) or an egg with no X chromosome at all (nullo-X). This is referred to as Non-disjunction. Fertilization of such abnormal eggs by normal sperms would produce zygotes with an abnormal number of sex chromosomes.
• If an egg with two X chromosomes (XwXw) is fertilized by a normal Y chromosome of sperm (Y), the zygote will be XwXwY. Since each of the X chromosomes in this zygote carries a mutant Xw allele, the resulting fly will have white eyes.
• If an egg without an X chromosome (O) is fertilized by an X-bearing sperm (Xw+), the zygote will be Xw+ O. (‘O’denotes absence of a chromosome.) Because the single Xw+ in this zygote carries mutant Xw+ allele, the zygote will develop into a red-eyed fly.
• It is inferred that XXY flies were female and that XO flies were male. The exceptional F1 white-eyed females that were observed were, therefore, XwXwY, and the exceptional F1 red-eyed males were Xw+O.
• Bridges confirmed the chromosome composition of these exceptional flies by direct cytological observation.
• As the XO animals were male, Bridges concluded that in Drosophila, the Y chromosome has nothing to do with the determination of the sexual phenotype. However, because the XO males were always sterile, he realized that this chromosome must be important for male sexual function.
• Bridges called the anomaly nondisjunction because it involved a failure of the chromosomes to disjoin during meiotic divisions.

5 Pedigree Analysis Eugenics Sir Francis Galton, 1883 proposed the idea of improvement in the human species through a change in hereditary characters in a scientific manner and named it ‘Eugenics’. Sir Francis Galton is thus known as ‘Father of Eugenics’. The study and analysis of human genetic studies are performed by many methods like pedigree analysis, statistical analysis and human karyotyping. Human Karyotyping

• Humans have 23 pairs (46) of chromosomes. In human karyotyping method, the chromosomes (autosomes and sex chromosomes) are arranged according to their size and structure.
• Based on the position of the centromere and relative lengths of both arms of the chromosome, three types of chromosomes are found in human beings. These are metacentric, submetacentric and acrocentric.
• A karyotype helps to know the relative structures of chromosomes. Besides, it helps in chromosomal identification and its nomenclature. It is also used in studying chromosomal abnormalities.

Pedigree AnalysisPedigree Inheritance of hundreds of characteristics such as polydactyly, haemophilia, colour blindness, attached earlobes and tongue rolling, generation after generation in particular families of man have been studied. A pedigree is a pictorial representation of family history, essentially a family tree that outlines the inheritance of one or more characteristics. To study and analyse, a pedigree of genetic facts/data and following symbols are used. Symbols used in Pedigree:

Patterns in Pedigree Analysis

1. Autosomal Dominant – affected individual will always have at least one affected parent.
2. Autosomal Recessive – affected individual will have unaffected parents and skipping of generation.
3. X-Linked Dominant – father is affected – all the daughters will be affected and no skipping of generation.
4. X-Linked Recessive – affected mother – all the sons are affected, criss cross inheritance from grandfather to carrier daughter to grandson.
5. Y-Linked Traits – father is affected – only sons will be affected.
6. Maternal Inheritance – affected mother – all the offspring affected and affected father – none of the offspring affected.

6 Genetic Disorders The genetic disorders may be grouped into two categories – Mendelian disorders and chromosomal disorders.

Mendelian Disorders Mendelian disorders are chiefly determined by alteration or mutation in the single gene. E.g., Haemophilia, cystic fibrosis, sickle cell anaemia, thalassemia, colour blindness, phenylketonuria, etc.

• Haemophilia: It is an inherited disorder of the blood in which an essential clotting factor is either partly or completely missing. This is a type of sex-linked recessive disorders. According to the genetic inheritance pattern, the unaffected carrier mother passes on the haemophilic genes to sons. It is a very rare type of disease among females because for a female to get the disease, the mother should either be haemophilic or a carrier but the father should be haemophilic. In this type of genetic disorder the affected gene is located on the X chromosomes. Males are thus more frequently affected as they have just one X chromosome.
• Sickle cell anaemia: The glutamic acid (glutamine) is replaced by valine at the sixth position in the β chain of haemoglobin. It is a disease of blood, where the red blood cells become sickle-shaped as compared to the normal biconcave shape.. This is a type of autosomal recessive genetic disorder. According to Mendelian genetics, its inheritance pattern follows inheritance from two carrier parents.
• Thalassemia is due to an autosomal mutant gene. It is a type of genetic disorder which results from the defective synthesis of subunits of haemoglobin (α and β globin chains of haemoglobin). It is an autosomal recessive disease.

Chromosomal Disorders

• Chromosomal disorders are due to absence or excess or abnormal arrangement of one or more chromosomes. Non-segregation of chromatids during cell division cycle results in the gain or loss of a chromosome(s), referred as aneuploidy. Types of chromosomal disorders include Down’s syndrome, Klinefelter’s syndrome and Turner’s syndrome.
• The numerical changes (chromosomal aberrations) can be classified as below:

Differences between Chromosomal and Mendelian Disorders

Chromosomal Disorders	Mendelian Disorders
Caused by chromosomal abnormalities.	Caused by allelic abnormalities.
Chromosomal abnormalities develop due to defective synapsis and disjunction.	Allelic abnormalities develop due to mutations.
The defect can be known through amniocentesis.	The defect can be predicted through pedigree analysis.
The disorder is rarely transmitted.	The disorder is transmitted to the progeny.

7 Sex Determination

Sex determination, in biology, is a system that decides the sexual characteristics of an organism or offspring. It helps to determine whether the organism will be male or female, which are the two most common sexes. 

Chromosomal Sex Determination

Humans have 23 pairs or 46 chromosomes. Of these 23 pairs, 22 pairs are known as autosomes whereas 1 pair is known as the sex chromosome. This one pair determines the sex of an individual. This was first studied by the German scientist Hermann Henking in 1891. He first noticed a different nuclear material in some of the male gametes in the insect he was studying. It was named the X chromosome. He also noticed that a large number of insects had only one chromosome and were denoted as XO. From here began the studies on sex determination of both sexes in all animals. 

Types of Sex Determination

The XX-XY system is seen in human beings, where, XX is the female and XY is the male. This is also seen in a few insects.

• The ZW-ZZ system is seen in birds, where ZW is the heteromorphic female and ZZ is the homomorphic male. This is also seen in some fishes and few insects.

• In the XO sex determination system which is found in several insects, females are still XX, but instead of carrying a Y chromosome, males simply carry a single X – the ‘O’ in ‘XO’ indicates the absence of a second sex chromosome.

• Haplodiploidy: Haploid-diploid mechanism or Haplodiploidy is a typical phenomenon in which an unfertilized egg develops into a male and a fertilized egg develops into a female. The female is thus diploid (2n), while the male is haploid (n). Fertilization restores the diploid number of chromosomes in the zygote; this zygote gives rise to the female. If the egg is not fertilized, it will still develop, but into a male (arrhenotoky or arrhenotokous parthenogenesis). It is seen in hymenopterous insects, such as bees, wasps, sawflies and ants.