Fundamentals of Genetics: Heredity and Variation

Introduction

Genetics is the scientific study of genes, heredity, and variation in living organisms. It is a field of biology that explores the mechanisms of inheritance, the transmission of traits from one generation to the next, and how genes influence the development, function, and evolution of organisms. In the 19th century, Gregor Mendel (1822-1884) conducted a series of experiments on pea plants, studying their inheritance patterns and developing the laws of heredity that are still widely used today. He was the first to systematically study the patterns of inheritance of traits in plants. Although Mendel’s work was not widely recognized during his lifetime, his experiments provided the foundation for the study of genetics and the development of the modern theory of inheritance. For his remarkable work, he is referred to as the “father of modern genetics.”

Mendel’s contribution

  • Mendel’s work eventually founded an entirely new branch of science – genetics. His ideas were published under the title “Experiments in plant hybridization” in the year 1866.
  • Mendel chose the garden pea, Pisum sativum plant for his genetic experiments.
  • The following are the reasons behind choosing the pea plant:
  1. It is easy to grow
  2. Flowers contain both male and female sex organs i.e., flowers are bisexual
  3. Self as well as cross-pollinating
  4. Short life span
  5. Several pairs of contrasting characters (Mendel used seven pairs only for his studies)
  6. No marked disturbance in their fertility in the successive generations

Characteristics used by Mendel in his experiments with pea plant

Characteristics

Dominant trait

Recessive trait

Plant height

Tall

Dwarf

Seed shape

Round

Wrinkled

Seed colour

Yellow

Green

Flower colour

Violet

White

Pod shape

Inflated (full)

Constricted

Pod colour

Green

Yellow

Flower position

Axial

Terminal

Mendel’s work remains largely unnoticed until 1900 till its rediscovery by three European botanists Hugo de Vries, Carl Correns and Erich von Tschermak. Using the consistent pattern of results, Mendel derived three postulates.

Mendel’s Postulates

Mendel’s three postulates are:

  1. The genetic characters are controlled by a pair of unit factors in individual organisms.
  2. When two different unit factors for a character are present in an individual, one may conceal the effect of the other.
  3. The paired unit factor randomly separates or segregates at the time of gamete formation so that each gamete receives one or the other unit factor.

Later the term unit factor was replaced by the term allele, which is a short form of allelomorph. This term was coined by William Bateson (1861-1926). He also coined the terms genetics, zygote, homozygote and heterozygote.

  • Based on Mendel’s observations, three laws have been put forward. These are called Laws of inheritance

Laws of inheritance

The First Law: Law of Dominance

  • In a heterozygote out of two different alleles, one can conceal the effect of the other.

The Second Law: Law of segregation:

  • During gamete formation, two alleles separate/segregate from each other.

The Third Law: Law of independent assortment:

  • Alleles of different genes separate/segregate/assort independently of each other.

Before going into the details of the laws of inheritance, let us discuss some important terminologies. It will help us to understand the laws better.

Gene

The unit of inheritance (DNA) is located in a fixed position on a chromosome. Or The hereditary determinant of a specific biological function.

Allele or Allelomorph

The alternate forms of a gene occur at the homologous position (locus) in a chromosome. There may be two or more than two alleles of a gene but in a diploid organism, only two can occur.

Diploid

An organism or cell with two sets of chromosomes (2n) or two genomes. Examples: TT, Tt etc.

Haploid

An organism or cell with only one set of chromosomes (n) or one genome only. Example: Gametes are always haploid.

Triploid, Tetraploid and Polyploid

The organism with Three (3n), Four (4n) and many sets of chromosomes respectively. Example: Banana is 3n; Salmonidae fish and cotton Gossypium hirsutum is 4n; Kenai Birch Betula papyrifera var. kenaica is 5n and wheat Triticum aestivum is 6n.

Genotype

The genetic constitution of an organism. The genotype is translated into phenotype Example: TtRrYy.

Phenotype

The observable characters. Example: Tall, curly hair and blue eye.

Dominant

In a heterozygote, the allele which expresses itself phenotypically is called the dominant allele and the trait is called the dominant trait. Example: In Pisum sativum allele for tallness is dominant over its alternative form.

Recessive

The allele which can express itself phenotypically only in the homozygous condition is called a recessive allele and the trait is called a recessive trait. Example: In Pisum sativum allele for dwarfness is recessive.

Homozygote

When both the alleles of a gene present in an organism are same then the condition is called homozygous (adj.) and the organism is called homozygote for that gene. Example: TT or tt for height.

Heterozygote

When the two alleles of a gene present in an organism are different then the condition is called heterozygous (adj.) and the organism is called heterozygote for that gene. Example: Tt for height.

We will discuss more terminologies wherever required. Let us come back to Mendel’s law.

The first law of inheritance: Law of dominance

In a heterozygote out of two different alleles, one can conceal the effect of the other.

In a diploid organism, out of two different alleles of a gene, only one can express itself phenotypically and the effect of the other allele remains hidden.

Example: When true breeding tall and dwarf pea plants are crossed, all the plants in the first generation are tall. When two tall plants of the first generation are crossed, 25 % of the second generation plants will be homozygous tall and 50 % will be heterozygous tall and 25% will be dwarf.

A monohybrid cross representing dominant-recessive relationship
  • In a monohybrid cross, when two homozygotes with contrasting traits are crossed; all the offspring of the first generation (F1) show a dominant trait.
  • When two heterozygotes of the first generation (F1) are crossed, the observed phenotypic ratio is 3:1 i.e. 3 (dominant):1 (recessive) and the genotypic ratio is 1:2:1 i.e. 1 (homozygous dominant):2 (heterozygous dominant):1 (recessive).
  • In a cross with the tall plant with the dwarf plant, all the F1 offsprings are tall. When two F1 individuals are crossed, there are 3 tall plants and 1 dwarf plant. Also, among the tall plants 1 is homozygous and 2 are heterozygous and one plant is dwarf which is always homozygous (in the case of the pea plant).

The second law of inheritance: Law of segregation

During gamete formation, two alleles separate/segregate from each other. An allele is transmitted faithfully from one generation to the next. Because each gamete receives only one allele of a given gene, this is also called the Law of purity of gametes. The basis of this phenomenon is the pairing and subsequent separation of the homologous chromosome during meiosis.

The third law of inheritance: Law of independent assortment

Alleles of different genes assort independently of each other. The different pairs of chromosomes behave differently during meiosis, which is the basis of independent assortment. However, there are genes which do not abide by this rule.

A monohybrid cross showing segregation and reunion of alleles of a gene

In the above monohybrid cross,

Phenotypic ratio = 3:1

and

Genotypic ratio = 1:2:1

In a Dihybrid cross where two genes are considered together, the ratios are different. To find out the genotypic and phenotypic ratios, consider a dihybrid cross between individuals of F1 generation of two pure line Pea plants; a tall one with violet flowers and another dwarf with white flowers.

A dihybrid cross between two pure line individuals

A cross between double heterozygous individuals TtVv and TtVv is shown below

A dihybrid cross between double heterozygous individuals (obtained in the previous cross) showing independent assortment of genes

Phenotypic ratio = 9:3:3:1

And

Genotypic ratio = 1:2:1: 2:4:2: 1:2:1

  • In the above cases of monohybrid and dihybrid crosses, the genes follow a simple Mendelian inheritance pattern. But the ratios will be different from expected when it involves linked genes or genes showing phenomena like Lethality, Codominance or Incomplete dominance etc.

Mutation

Sudden, inheritable changes in the genetic material are called a mutation. Later, we will discuss mutation in detail.

Lethal mutation

Thousands of gene products are required by an individual. Some are essential and some are non-essential. Loss of function mutation (non-functional gene product), in a gene providing the essential product, causes the death of the individual if it is not compensated by another gene product.
It can be classified into two types: i). Recessive lethal and ii). Dominant lethal

i). Recessive lethal:

Mutation(s) creating a non-functional or partially functional gene product tolerated in heterozygous condition, but not in the homozygous recessive condition such mutations behave as recessive lethal. However, the phenotypic effect of such mutations can be dominant.

Example: Mutation which causes yellow coat colour in mice (yellow lethal mutation). This is a loss-of-function as well as a gain-of-function mutation. The heterozygote A+Ay synthesizes yellow pigment which is deposited in the hair shaft, resulting in yellow coat colour. This effect is due to the gain of function mutation. Due to the deletion of a segment in the Ay allele which extends to the coding region of the MerC gene, rendering it non-functional. Because of its critical role in embryonic development, AyAy individuals die in the embryonic stage. The coat colour in mice is of two types agouti (grey-brown) and yellow and it is controlled by gene A. The A+A+ individuals are agouti while A+Ay is yellow. The cross between two agoutis; agouti and yellow and two yellow individuals are shown below.

Cross showing effect of lethal gene

ii). Dominant lethal:

Mutation(s) creating a non-functional or partially functional gene product or the product of a mutant gene somehow overrides the function of a wild-type gene. It is not tolerated even in heterozygous conditions; such mutations behave as dominant lethal.

Example: Huntington’s disease in humans. It is caused by a dominant allele H. The onset of the disease is usually late (around 40 years). The affected individual gradually undergoes nervous and motor degeneration and dies.

How do lethal mutations exist in the population?

The recessive lethal mutation causes death in homozygous conditions but not in heterozygous conditions therefore, it can exist in heterozygous conditions. For the existence of dominant lethal mutations individuals must reproduce before dying.

Incomplete dominance

If the phenotype of the heterozygote is intermediate to either of the associated homozygote, the phenomenon is called incomplete or partial or semi-dominance.

Example 1: Flower colour of Snapdragon Antirrhinum majus. It is red (CRCR), white (CWCW) and pink (CRCW).

Reason− The intermediate colour in the heterozygote is due to the pigment (anthocyanin) produced by the red allele being diluted in the heterozygote and therefore appears pink because of the white petals.

Cross showing Incomplete dominance

Example 2: inheritance of straight, wavy, and curly hair in dogs. Members of the KRT gene family synthesize keratin proteins present in hair skin and nails. A mutation in exon-2 of the KRT71 gene disrupts keratin71 protein structure which results in the alteration of hair structure and causes a curly coat. Dog with the KCKC genotype has a very curly coat; K+K+ has a straight coat and K+KC have an intermediate or wavy coat.

  • The ratios are similar to that of the genotypic ratio of the Mendelian monohybrid cross (dominant-recessive relationship).
  • The feather colour of Andalusian chickens (white, blue & black); Fur length in Angora rabbits (long, intermediate & short); coat colour in horses (red, golden & cream) are other examples of it.

Co-dominance

When the different alleles of a gene express themselves phenotypically as they do in homozygous conditions, these are called co-dominant alleles and this phenomenon is called co-dominance. In co-dominance, neither allele mask the expression of the other allele.

Example: Roan coat colour in cattle, MN & AB blood groups in humans etc.

How codominance is different from incomplete dominance?

In partial dominance, the dominant allele cannot entirely hide the expression of the recessive allele and an intermediate phenotype is observed. In co-dominance both the alleles in a heterozygote express phenotypically at some extant. In both cases, the genotypic and phenotypic ratios of a cross between two heterozygotes are 1:2:1.

Multiple alleles

When there are more than two alternate forms (alleles) of a gene, these are called multiple alleles and the phenomenon is called multiple allelism. It can be observed in a population only.

Example: Coat colour in rabbits and ABO blood group in humans are classic examples of multiple alleles. The coat colour of rabbits is controlled by gene “c”. There are four alleles of this gene, c+ (Wild type), ch (Himalayan), cch (Chinchilla) and c (Albino). The c+ allele is completely dominant over all other alleles, cch allele is partially dominant over ch & c and ch is completely dominant over allele c. Therefore, the genotypes c+c+, c+ch, c+cch & c+c show wild type coat colour; cchcch, cchcc & cchc shows chinchilla coat colour; chch & chc shows Himalayan coat colour and cc shows albino coat colour.

ABO blood group in human is another example of multiple allelism. Read about blood groups in human here.

Pleiotropy

The term pleiotropy means multiple effects. Greek; pleio, means ”many” and tropic, means “affecting.” Thus Genes that affect multiple, apparently unrelated, phenotypes are called pleiotropic genes.

Example 1: Amino acid Tyrosine is required for protein synthesis and it is the precursor for neurotransmitters like dopamine and norepinephrine, the hormone thyroxine, and the pigment melanin. Mutation in the gene involved in Tyr synthesis/metabolism may affect multiple body systems.

Example 2: In Drosophila The vestigial gene “vg” is critical for wing development. Flies homozygous for the recessive “vg” allele develop short wings and are unable to fly as a direct result. But, the gene also changes the number of egg strings in the fly’s ovaries, alters the position of bristles on the fly’s scutellum, and decreases the length of the fly’s life.

Pleiotropy in Humans:

There are many pleiotropic genes in humans. But the most cited one is phenylketonuria (PKU). This disease is caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH) which converts phenylalanine (Phe) to tyrosine (Tyr) and ultimately leads to the complete oxidation of Phe to CO2 and H2O. Mutation in enzyme PAH leads to the accumulation of phenylalanine which is then converted into phenylpyruvate, phenyl lactate, and O-hydroxy phenylacetate. These metabolites are excreted in the urine. Symptoms: Untreated PKU can lead to growth failure, microcephaly, seizures and intellectual impairment caused by the accumulation of toxic by-products of Phe. Decreased or absent PAH activity can lead to the deficiency of Tyr and its downstream products, including melanin, l-thyroxine and the catecholamines neurotransmitters.

Another example of pleiotropy in humans is Marfan syndrome; An autosomal dominant disorder of connective tissue, caused by a mutation in the FBN1 gene. The symptoms include myopia (nearsightedness from the increased curve of the retina due to connective tissue changes in the eyeball), bone overgrowth and loose joints (joint laxity), Cardiovascular malformations etc.

References:

  • Brenner, S., Miller, J. H., & Broughton, W. J. (2002). Encyclopedia of genetics. In Academic Press eBooks. http://ci.nii.ac.jp/ncid/BA5446428X
  • Rédei, G. P. (2008). Encyclopedia of Genetics, Genomics, Proteomics and Informatics. In Springer eBooks. https://doi.org/10.1007/978-1-4020-6754-9
  • Krebs, J. E., Lewin, B., Goldstein, E. S., & Kilpatrick, S. T. (2012). Lewin’s Genes XI. Jones & Bartlett Publishers.
  • Klug, W. S., & Cummings, M. R. (1983). Concepts of genetics.
 

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