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PRINCIPLES OF INHERITANCE AND VARIATION

Genetics Genetics is the branch of science which deals with the inheritance and variation of characters from parent to offspring. Inheritance It is the process by which characters are passed on from parent to progeny. Variation It is the degree by which progeny differ from their parents. Gregor Johann Mendel Mendel was an Austrian Monk who is considered as the father of genetics Mendel conducted so many hybridization experiments with garden pea plant and proposed the famous Mendels laws of Inheritance Mendels experimental material The experimental material selected by Mendel was garden pea plant Pisum sativum. The garden pea plant was true breeding variety. True breeding plants are the plants which undergo continuous self pollination and shows stable trait inheritance for several generations. The garden pea contains large number of contrasting characters and out of which Mendel selected only seven characters. Each character has two alternatives or verities Contrasting traits studied by Mendel in pea plant

INHERITANCE OF ONE GENE To study inheritance of one gene Mendel crossed tall and dwarf pea plants. The seeds produced as a result of this cross are collected and grew. This hybrid generation is called Filial1 progeny or the F1 generation. Mendel observed that all the F1 progeny plants were tall .No dwarf is observed. Mendel the self pollinated the tall F1 plants and F2 generation is produced. In the F2 generation he got tall and dwarf plants in the ratio 3:1 ie, 75% tall plants and 25% dwarf plants. He got similar results with other traits also The character in the F1 and F2 generation did not show any blending at either F1 or F2 stage ie, they are identical to the parental type.

2 Genes Based on the observations of Mendels experiments he proposed that something was being stably passed down, unchanged from parent to offspring through gametes. Mendel called these things as factors and now they are called as genes. Genes are the units of inheritance which contain the information for the expression of a particular trait in an organism. Alleles Genes which code for a pair of contrasting traits are known as alleles. ie they are slightly different forms of the same gene . Dominant character The character which is expressed in one generation is called dominant character. The dominant gene is named by the first letter of the dominant character in capital form. Eg. The character height or tall is expressed by the symbol T. Dominant alleles for height are TT and Tt Recessive character The character which is not expressed in one generation is known as recessive character. The recessive gene is named by the first letter of the recessive character in small form. Eg . The character height or tall is expressed by the symbol t The recessive allele for height is tt Homozygous alleles The identical pair of alleles is called homozygous alleles. Eg ; TT represents tall Tt represents dwarf Heterozygous alleles The contrasting pair of alleles is called heterozygous alleles. Eg ; Tt has both dominant and recessive allele Phenotype The external appearance of an organism is called phenotype Eg . tall , dwarf , red flower , violet flower , round seed , wrinkled seed, axial flower , terminal flower etc. Genotype The genetic make up of an organism is the genotype. Eg ; TT and Tt express the tall genotype. Monohybrid cross A cross involving two plants differing in one character pair is called monohybrid cross. Mendel crossed a tall plant with a dwarf plant The hybrid progeny of F1 generation were all tall plants. ie, tall is the dominant character and dwarf is the recessive character. Mendel selfed the F1 plants and raised the F2 generation and got tall and dwarf plants in the ratio 3:1. This shows that the recessive character dwarf is expressed in F2 generation During gamete formation, the alleles of the parental pair separate or segregate from each other and only one allele is transmitted to a gamete. Thus the gamete of the tall plants TT have the allele T and dwarf plants tt have the allele t . In F1 generation, during fertilization T from one parent fuse with t from the other and

3 PUNNET SQUARE The production of gamete by the parents, the formation of the zygote, the F1and F2 plants can be understood from a diagram called punnett square. It was developed by British geneticist, Reginald C Punnett. It is a graphical representation to calculate the possibility of all possible genotype of offsprings in a genetic cross The possible gametes are written on two sides, usually the top rows and left columns. All possible combinations are represented in boxes below in the square. Expressions of monohybrid cross in Punnett square The punnett square or checker board shows the parents; tall TT (male) and dwarf tt(female) plants ,the gametes produced by them and the F1 Tt progeny. The F1 plants are then self pollinated. Self pollination produces gametes of the genotype T and t in equal proportions. The resultant zygotes have the genotypes TT , Tt and tt. 1/4th of the progeny is TT , 1/2 is Tt and 1/4th is tt . This gives the genotypic ratio 1TT: 2Tt : 1tt (1:2:1) and phenotypic ratio 3Tall: 1Dwarf (3:1) T is the dominant allele.So the genotypes TT and Tt are phenotypically Tall. TEST CROSS It is the crossing of an F1 hybrid with its recessive parent . The test cross is used to find out whether the dominant individual is homozygous or heterozygous . In a typical test cross dominant individual is crossed with the recessive parent . If the dominant plant is homozygous it will produce only one type of progeny. If the dominant plant is heterozygous it will produce two type of progeny in the 1:1 ratio . This ratio is called typical monohybrid test cross ratio. Example for test cross To find out the genotype of dominant violet flowered plant (whether WW or ww), it is crossed with homozygous recessive white flowered plant (ww). If the dominant violet flowered plant is homozygous (WW) all the progeny produced will have the genotype Ww and phenotype violet flower. If the dominant violet flowered plant is heterozygous (Ww) the progeny will have the genotype Ww and ww and phenotype violet and white in the ratio 1:1 Mendels laws of inheritance Based on the observations on monohybrid crosses Mendel proposed two general rules of inheritance known as principles or laws of inheritance , They are, 1.First law or Law Of Dominance 2. Second law or Law Of Segregation LAW OF DOMINANCE This law states that the characters are controlled by discrete units called factors which occur in pairs. If the factors for a character is dissimilar , one member of the factor dominate over the other .

4 The law explains the expression of only one of the parental characters in a monohybrid cross in the F1and the expression of the both in the F2 It also explain the proportion of 3:1 obtained at the F2. LAW OF SEGREGATION This law states that during gamete formation , the two factors for a character present in an individual will separate and segregate with each other . So that a gamete receives only one of the two factors. As per this law, a homozygous parent produces all gametes that are similar while a heterozygous one produces two kinds of gametes each having one allele with equal proportion. INCOMPLETE DOMINANCE The type of inheritance in which the F1 phenotype do not resemble either of the two parents but shows an intermediate character is called incomplete dominance Eg ; The inheritance of flower colour in snap dragon ,Antirrhinum majus In a cross between homozygous red flowered plant (RR) with homozygous white flowered plant(rr) the F1 (Rr) was pink instead of red . When F1was self fertilized the F2 resulted the following ratio1Red (RR) : 2Pink(Rr) : 1White. Here the genotypic and phenotypic ratio is 1:2:1. This happens because R was not completely dominant over r . So Rr shows an intermediate pink colour . Explanation of the concept of dominance Every gene contains the information to express a particular trait. In a diploid organism, the genes occurs in pairs known as alleles . The alleles for a particular trait need not be always identical. One of them may be different due to some changes that it has undergone. This changes modifies the information that particular allele contains. CO DOMINANCE In Co-Dominance the F1 generation resembles both the parents. Eg : ABO- Blood group in human beings The blood group determining sugar polymers are present in the plasma membrane of RBC and which is controlled by the gene I. The gene I has three alleles IA , IB and i. The alleles IA and IB produce different sugars , while the allele i does not produce any sugar. Each person has any two of the 3 alleles. Both IA and IB are dominant over I , ie, if IA and i together present in a person only IA expresses. But IA and IB are co- dominant , ie , they both express their own types of sugars. Since there are 3 different alleles, there are 6 different combinations and a total of six different genotypes.

5 Genetic basis of blood groups in human beings

Multiple alleles More than two alleles of a gene are called multiple alleles and the phenomenon is called multiple allelesim. ABO-Blood group in man is an excellent example for multiple allelism . Here three alleles determine the same character. This system was discovered by Karl Landsteiner in 1900. INHERITANCE OF TWO GENES (DIHYBRID CROSS) Mendel selected two characters together in another experiment known as dihybrid cross. He selected two characters namely the seed colour (yellow and green) and seed shape (round and wrinkled) of the pea plant Yellow colour (YY) and round shape (RR) is dominant over green colour (yy) and wrinkled shape(rr). In the first step Mendel crossed round yellow seeds (RRYY) with wrinkled green (rryy)seeds In the F1 generation all the seeds were round yellow with the genotype RrYy,showing the dominant characters. In the second step,F1 offsprings were self fertilized and F2 generation was made . In F2 generation, Mendel observed 4 types of plants 2 were parent like (round yellow and wrinkled green) and other 2 were recombinant type (round green and wrinkled yellow). LAW OF INDEPENDENT ASSORTMENT Based upon the observation on dihybrid crosses Mendel proposed a second law known as law of independent assortment. This law states that When two pairs of traits are combined in a hybrid, segregation of one pair of characters is independent of the other pair of characters Explanation of Law Of Independent Assortment with Punnett square The Punnett square can be used to understand the independent segregation of the two pairs of genes during meiosis and the production of eggs and pollen in the F1 hybrid RrYy plant. The F1 hybrid Rr Yy plant produces four types of gametes such as RY , Ry , rY and ry . The cross of two such plants produce 16 combinations as per the table in the next page. Out of the 16 combinations 9 are round yellow because they have both dominant genes R and Y.

6 3 combinations are round gene, because they have dominant R gene for round and recessive gene for green (yy). Other 3 combinations are wrinkled yellow because they have dominant gene for yellow(Y) and recessive gene for wrinkled shape (rr). One combination is wrinkled green because it has both recessive gene r and y. Thus the phenotypic ratio of dihybrid cross is 9:3:3:1 (9round yellow: 3round green: 3wrinkled yellow: 1 wrinkled green). The genotypic ratio of dihybrid cross is 1: 2: 1 : 2 : 4 : 2 : 1 : 2 : 1 ie 1 RRYY (round yellow) : 2 RrYY(round yellow) : 1 rrYY (wrinkled yellow) : 2 RRYy (round yellow) : 4 RrYy (round yellow) : 1 RRyy (round green) : 2 rrYY (wrinkled yellow) : 2 Rryy(round green) : 1 rryy (wrinkled green).

7 CHROMOSOMAL THEORY OF INHERITANCE Even though Mendel published his work in 1865, it remained unnoticed till 1900.This is because, 1. Communication was not easy in those days to inform the findings to the scientific world. 2. His concept of genes (factors) as stable and discrete units that controlled the expression of traits and the alleles blend with each other was not accepted by the contemporaries as an explanation for the variation seen in nature. 3. His approach of using mathematics to explain biological phenomena was totally new and unacceptable to the scientists of his time. 4. He could not provide any physical proof for the existence of factors. In 1900, three scientists (Correns, de Vries and Tschermark) independently rediscovered Mendels results on the inheritance of characters. By that time scientists observed cell division, nucleus and chromosomes. Sutton and Bovery explained the chromosome theory of inheritance in 1902. They noted that the behavior of chromosomes was parallel to the behaviour of genes and they used chromosome movement to explain Mendels laws. Principles of chromosome theory of inheritance 1. Chromosomes occur in pairs. 2. The two alleles of a gene pair are located in homologous in homologous sites on homologous chromosomes. 3. During gametogenesis, each gamete will receive only one member from a homologous pair.(eg : 23 chromosomes in man) 4. Each chromosome has its own individuality, ie, a particular chromosome is different from other chromosome in size, shape, structure, arrangement of genes etc. Comparison between the behaviour of chromosomes and genes Chromosomes Genes

Contribution of T.H .Morgan in Genetics The experimental verification of chromosomal theory was done by TH Morgan and his colleagues. This led to the discovery of the basis of variation seen in sexual reproduction. The experimental material used by Morgan is the tiny fruity fly, Drosophila melanogaster Drosophila melanogaster is the best material for genetic study ,Why? 1. They could be grown on simple synthetic medium in the laboratory. 2. They complete their life cycle in about 2 weeks. 3. Single mating could produce a large number of progeny flies .

8 4. Sex determination is clear the male and female flies are easily distinguishable. 5. It has many types of hereditary variations that can be seen with low power microscope. LINKAGE AND RECOMBINATION Organisms have numerous characters and the genes responsible for these characters are located on chromosomes. So a single chromosome carries many genes, ie, the genes are linked together to some extent. Linkage is the phenomenon of co-existence of two or more genes in the same chromosomes. Such genes are called linked genes . Linked genes do not show independent assortment. Example for linkage Morgan hybridized yellow- bodied, white- eyed females to brown bodied, red-eyed males and then intercrossed their F1 progeny. He observed that the two genes did not segregate independently of each other and the F2 ratio deviated very significantly from the 9:3:3:1 ratio expected. This happened because the genes were located on the X- chromosomes. Thus when two genes in a dihybrid cross were situated on the same chromosomes, the proportion of the parental gene combinations was much higher than the non-parental type due to linkage. Recombination The term recombination is used to describe the generation of non-parental combinations. Characteristics of linkage Linkage is mainly determined by the distance between the genes in a chromosome. The tightly linked genes show very low recombination frequency. The recombination frequency is only 1.3% in tightly linked genes of white and yellow and 98.7% is parental type in the drosophila. The loosely linked genes show high frequency of recombination. White and miniature wing showed 37.2% recombination. Here parental type is only 62.8%. (Refer text book page 84, figure 5.11) SEX DETERMINATION Henking in 1891 observed that during spermatogenesis 50% of sperm received a specific nuclear structure and the other 50% did not receive it. Henking gave a name to the nuclear structure as the X-body, but he could not explain what xbody was. Further it is identified that the X-body is a chromosome and for sex determination given the name X-chromosome XX-XO Mechanism of sex determination In many insects and round worms xx-xo sex determining mechanism is seen. Here females produce one type of egg with one x chromosome While males produce two types of sperms- one with x-chromosome and the other without an xchromosome. Fusion of x-sperm with x-egg produces females (xx) and fusion of o-sperm with x-egg produces a male (xo). Eg ; grass hopper

9 XX-XY Mechanism In mammals and drosophila xx-xy mechanism is seen. Here females are xx and males are xy. Males produce two types of sperms one with x-chromosome and the other with y chromosomes. The fusion of x-egg with y-sperm produces xy males. ZZ-ZW mechanism This type sex determination is mainly seen in birds. Here females are heterogametic. They produce two types of eggs; one with Z chromosome and the other with W chromosome. Males are homogametic and produce sperms with only Z-chromosomes. Fusion of Z-sperm with Z-egg produce males(ZZ) and the fusion of Z-sperm with W-egg produces a female(ZW). Thus in birds the egg is responsible for the sex of the chicks. Sex determination in human beings (refer : human reproduction chapter) MUTATION Mutations are the sudden heritable changes in the genotype of an organism. Mutation theory was proposed by Lamark in 1901. Changes due to mutation occur as a result of deletion (loss) or insertion /duplication (gain) of a segment of DNA Types of mutation 1. Point Mutation Mutation arise due to change in a single base pair of DNA 2.Frame shift mutation Mutation arising due to deletion and insertion of base pairs of DNA Mutagens The chemical and physical factors which induce mutations are known as mutagens Eg ; UV radiations GENETIC DISORDERS PEDIGREE ANALYSIS Analysing the inheritance of the character through several previous generations in a family is known as pedigree analysis . In this the inheritance of a particular trait is represented in the family tree over generations. The ancestral history of an individual is called pedigree. In the pedigree analysis the studies of trait, as they have been appeared in a given family line for several past generations can be done.

10 Symbols used in the human pedigree analysis

MENDELIAN DISORDERS Genetic disorders are broadly classified into two categories Mendelian disorders and chromosomal disorders . Mendelian disorders occur due to alteration or mutation in the single gene. These disorders are transmitted to the offspring as in the principle of inheritance and can be traced using the pedigree analysis.

11 Examples of mendelian disorders Most common mendelian disorders are haemophilia , cystic fibrosis, sickle cell anaemia, colour blindness, phenyl ketonuria, thalasemia etc. Mendelian disorders may be dominant or recessive and by pedigree analysis it can be found out. These traits are sex linked as in the case of haemophilia. The X- linked recessive trait shows transmission from grand father to grandson through daughter (criss cross inheritance) HAEMOPHILIA Haemophilia (Bleeders disease) is a hereditary sex- linked blood disease in man. The affected person may die due to minor injuries because of excessive bleeding. This is caused by the absence of a blood clotting factor- antihaemophilic factor . The genes responsible for haemophilia are located on the X-chromosomes . The Y-chromosome carries no genes for this trait . The heterozygous females are carriers for haemophilia and they transmit the disease to sons.(criss- cross inheritance pattern) If a normal woman marries a haemophilic man, all their daughters are carriers of disease because father passes his X-chromosome only to his daughters. Since the Y-chromosome of father has no gene for the trait their sons will be normal. If a carrier woman marries a normal man, 50% of their daughters are normal and 50% will be carriers . In the same way 50% of sons will be normal and 50% will be haemophilic. Haemophilic sons gains haemophilic gene containing X- chromosome from the mother. SICKLE CELL ANAEMIA This is a genetic defect characterized by sickle shaped RBC with abnormal haemoglobin which is unable to carry oxygen. In this disease sickle shaped RBCs are rapidly destroyed than the normal RBC leading to anaemia. This is an autosome linked recessive trait that can be transmitted from parents to the offspring when both the partners are carriers for the gene(heterozygous). This disease is due to the gene mutation that causes the substitution of a wrong amino acid valine instead of glutamic acid in the 6th position of the beta chain of haemoglobin of RBC. This disease is controlled by a pair of alleles HbA and HbS. Out of the 3 possible genotypes (HbAHbA, HbAHbS, HbSHbS) the first one is normal, second is carrier and 3rd is affected (homozygous) exhibiting sickle cell anaenmia.

12 PHENYLKETONURIA This is an inborn error of metabolism in which the affected individual lacks an enzyme which converts the aminoacid phenyl alanine into tyrosine. As a result of this phenyl alanine is accumulated and converted into phenyl pyruvic acid and other derivatives. These are also excreted through urine because of its poor absorption by kidney. Accumulation of phenyl alanine in brain results in mental retardation. CHROMOSOMAL DISORDERS Chromosomal disorders are caused due to the absence or excess or abnormal arrangement of one or more chromosomes. This mainly occurs due to the failure of segregation of chromatids during cell division. Aneuploidy The gain or loss of a chromosome is called aneuploidy Two types of aneuploidy 1. Trisomy The presence of an additional copy of chromosome is trisomy Eg; Down syndrome 2. Monosomy The loss of one chromosome is monosomy. Eg : turner; s syndrome Polyploidy Increase in a whole set of chromosome is called polyploidy. This is due to failure of cytokinesis after telophase stage of cell division. DOWN S SYNDROME (45 AUTOSOMES+XX OR XY) This genetic disorder is due to the trisomy of chromosome No. 21 This disorder was first described by Langdon Down. The affected individual is short statured with small round head, furrowed tongue and partially open mouth. Physical, mental and psychomotor development is retarded KLINEFELTERS SYNDROME (44 AUTOSOMES +XXY) This genetic disorder is caused due to the presence of an additional copy of X-Chromosome. The affected individual has overall masculine development with female characteristics(development of breast-Gynaecomastia) is observed. Such individuals are sterile also. TURNERS SYNDROME (TOTAL 45 CHROMOSOMES (44 AUTOSOMES +XO)) This genetic disorder is caused due to the absence of one of the X-chromosomes. Such females are sterile with rudimentary ovaries and they also lack secondary sexual characters. Notes Prepared by Biju T L HSST Zoology GHSS MYlachal, Tvpm