Unit 2: Extension & Modifications of Mendelian Genetic Analysis-I PDF

Block 1 Heredity and Phenotype UNIT 2 EXTENSION & MODIFICATIONS OF MENDELIAN GENETIC ANALYSIS...

Block 1 Heredity and Phenotype UNIT 2 EXTENSION & MODIFICATIONS OF MENDELIAN GENETIC ANALYSIS ANALYSISI Structure 2.1 Introduction Epistasis Objectives Supplementary Gene Interaction 2.2 Dominance Duplicate Genes Complete Dominance (Pseudoalleles) Incomplete Dominance 2.5 Lethal Alleles (Blending Inheritance or Semi/Intermediate 2.6 Pleiotropy Dominance) 2.7 Sex-Linked Genes Codominance 2.8 Degrees of Gene 2.3 Multiple Alleles Expression ABO Blood Type Alleles in Penetrance Humans Expressivity Rh Factor Alleles in Humans 2.9 Summary Incompatibility in Plants 2.10 Terminal Question 2.4 Gene Interactions and 2.11 Answers Modified Mendelian Ratios Complementary Gene Interaction (9:7 Phenotypic Ratio) 2.1 INTRODUCTION In the previous unit you have been introduced to the concept of genetics and as to how it has developed unto full fledged discipline of genetics with the 46 Mendel’s work on garden pea. The secret of inheritance mechanism of all the Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I traits or characters in an organism, from parents to off-springs, lies in the genes. It is now an established fact that the segments of DNA express in a very well defined manner to produce a trait or character. Each gene has two alternative forms called alleles, each of which occurs at the same locus in each homologous chromosome. As you all know, the term ‘allele’ comes from ‘allelomorph’ and refers to the different forms of a gene which affect a phenotype in an organism. Thus number of allelic forms of a gene may be many in a population, but since each organism has only one pair of homologous chromosome of a kind, only two of its variants are present in an organism. Various interactions may occur between alleles of same genes or alleles of different genes, which give rise to different phenotypes, making the inheritance patterns complex. The phenotypic expression of these characters could not be explained by Mendel’s laws alone and thus this has opened a whole new myriad of allelic and non-allelic interactions. This unit explains the deviations from Mendelian principles, its extensions and modifications that have led to the occurrence of different phenotypes in a progeny as compared to their parents. Broadly categorizing, such interactions can be classified as- 1) Intragenic interactions: When the two alleles of same gene interact with each other and affect a phenotype, it is known as inter-allelic, allelic gene or intragenic interactions, for examples- incomplete dominance, co- dominance and multiple alleles. 2) Intergenic interactions: If the alleles of different genes, located on separate loci, interact with each other and influence a phenotype, it is known as non-allelic or intergenic interactions. For example- complementary gene interaction, epistasis, supplementary gene interaction and duplicate genes. Objectives After studying this unit, you should be able to:
define various terms related to intergenic and intragenic interactions,
understand the concepts underlying the modifications of Mendelian genetics,
analyse the influence of various interactions among alleles and genes on a phenotype,
distinguish among different allelic and non-allelic gene interactions, and
explain the phenomena of production of new phenotypes. 2.2 DOMINANCE We have studied in the previous unit that Gregor Mendel's experiments laid the very basis of the concepts of heredity, however, these studies were confined to the seven traits of pea plant, the conclusions were also restricted to the observations obtained thereof. The only relationship established by 47 Block 1 Heredity and Phenotype Mendel between the factors or alleles of a trait was dominance and recessiveness. This simplicity of the Mendel’s principles also come from the fact that the inheritance patterns of the seven traits selected by Mendel were fortunately all straight forward and showed no complexities. Later when the study was extended to other traits or organisms, it became evident that the inheritance patterns are far more complex than the simple genetic pattern described by Mendel. A variety of new traits and characters were investigated which were the result of some undefined genic/allelic interactions. Let us discuss the Mendelian concept of complete dominance and its modifications- incomplete dominance and co-dominance. 2.2.1 Complete Dominance Complete dominance, as inferred by Mendel, refers to the type of dominance in which one allele completely masks the expression of other allele and is therefore said to be completely dominant. The allele which is masked or remains unexpressed is called recessive. The genotype of organism exhibiting complete dominance is heterozygous.A dominant feature of a trait is represented by allele ‘A’ and its recessive feature by allele ‘a’. The homozygous condition ‘AA’ is responsible for its prominent phenotype while ‘aa’ gives its contrasting phenotype. When both the alleles appear together in heterozygous condition (Aa), the expression of ‘a’ is completely masked and only the phenotype of ‘A’ is visible. In such a case the allele ‘A’ is said to be completely dominant over allele ‘a’, and thus ‘a’ is said to be recessive. Phenotypically, dominant characters can be easily recognized because they are expressed even if one dominant allele is present. Recessive alleles need to come in pair for expression, therefore, they can be recognized only in homozygous individuals (aa). Thus the heterozygous individuals, who are the carriers of recessive allele, are not recognizable on the basis of phenotype, however, can be identified through test cross. In test cross potential carriers are crossed with homozygous recessive individuals to know their in genotype (Fig. 2.1). The relationship of dominance and recessiveness, as deduced by Mendel, can be explained by taking example of seed shape in pea plants. The seeds in pea plant can be of any of the two shapes- round or wrinkled. The allele assigned to round seed shape is ‘R’ while allele for wrinkled seed shape is ‘r’. If a monohybrid cross is performed between a plant homozygous for round seeds (RR) with another plant homozygous for wrinkled seeds (rr), the F1 generation completely resembles the parents with dominant phenotype i.e. round seeds. In heterozygous plants ‘Rr’, the round shape of seeds completely masks the wrinkled phenotype. Thus allele ‘R’ for round shape was said to be dominant over wrinkled ‘r’. The dominant- recessive pattern as inferred by Mendel was too straightforward and does not always exhibit as such. The observable phenotype may occur due to the influence of different environmental factors or other genic or intergenic interactions. In case of inheritance of seed shape in peas, the round and wrinkled phenotypes are acquired due to biosynthesis of amylopectin, a branched chain component of starch. The biosynthesis of 48 amylopectin occurs by the action of starch-branching enzyme I (SBE-I), and Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I the activity of this enzyme affects the amount of amylopectin deposition in seeds. The presence of amylopectin helps in adequate retention of water so that while maturation of seeds the shrinkage is uniform and they acquire a round shape. In homozygous RR seeds gene for SBE-I enzyme at ‘r’ locus was found to be fully functional, and in heterozygous Rr seeds it was partially functional. However, in homozygous rr seeds, the SBE-I gene function was found to be interrupted due to insertion of a small DNA sequence and these seeds completely lacked amylopectin. This led to an increase in amount of free carbohydrates and higher osmotic pressures. Therefore, when shrinkage started on maturation, abrupt loss of large amount of water led to acquisition of wrinkled phenotype in ‘rr’ seeds. Deep observation of all the phenotypes also revealed the amount of amylopectin and thereby the round shape of seeds in Rr was somewhat intermediate between RR and rr. The shape of starch grains was also quite distinct from each other in all the three genotypes. Fig. 2.1: Complete Dominance in inheritance of seed shape phenotype in Pea. Thus simply rendering the round / wrinkled phenotypes in pea seeds to the phenomenon of dominance was not justifiable and suggested for more insights into the genetic mechanisms. 2.2.2 Incomplete Dominance (Blending Inheritance or Semi/Intermediate Dominance) Another type of interaction between two alleles was discovered by Karl Correns in 1900, while experimenting with Four O’ Clock plant (Mirabilis jalapa belonging to family Nyctaginaceae). When he crossed the homozygous plant with red flowers (RR) with homozygous recessive plant with white flowers (rr), he noticed a strange phenotype in F1 hybrids. The flowers of heterozygous (Rr) plants were pink, instead of being red by virtue of dominance. He concluded that this was due to an intra-allelic interaction in which the dominant allele could express itself partially in heterozygous condition. Since the character appeared to be intermediate between the dominant and recessive phenotypes, the phenomenon was called ‘incomplete dominance’. 49 Block 1 Heredity and Phenotype Further, if selfing is done among F1 hybrids, the phenomenon of incomplete dominance persists and phenotypic and genotypic ratios obtained in F2 generation are Red1: Pink2: White1 (Fig. 2.2). 2.2.3 Codominance Codominance is a phenomenon in which both the alleles are completely expressed in the heterozygous condition, the phenotype of the heterozygous individual is a mixture of both. Since the characters expressed by both the alleles exist simultaneously in equal amount, there is no appearance of intermediate phenotype in heterozygotes as is seen in incomplete dominance. Codominance is observed in the MN blood groups of humans. This classification of human blood is based on the presence of M and N antigens on the surfaces of red blood cells. The M and N antigens are produced by a pair of codominant alleles designated as LM & LN. The homozygous condition of allele LM produces marker antigen M, while an LN produces marker antigen N, on the surface of red blood cells. Homozygotes LMLM have only M while LNLN have only N markers, however, heterozygotes L M N L have both types of marker antigens in equal amounts on the cell surface. If a cross occurs between individuals with LMLN genotypes, the probablility of occurance of M, MN, and N blood types would be as given below: Red Pink White 1 : 2 : 1 50 Fig. 2.2: Incomplete Dominance in flowers of Mirabilis jalapa. Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I Table2.1: Codominance in the MN blood groups in humans. Genotype Phenotype Antigen present on RBCs LM LM M M LM Ln MN MN LM LN N N Another classical example of codominance is inheritance of colour of flower in Camellia plants. If white Camellia are crossed with red Camellia, the flowers produced in F1 generation produce flowers with mixed patches of red and white colour. The alleles for both red and white petal colour are codominant and both the colours are expressed simultaneously in equal amounts. Fig. 2.3: Codominance in Camellia flowers. SAQ 1 i) The allele which is masked or remains unexpressed is called ……………... ii) The flowers of heterozygous (Rr) plants were pink instead of being red by virtue of ……………….. iii) ………………. is a phenomenon in which both the alleles are completely expressed in heterozygous condition, the phenotype of heterozygous individual is a mixture of both. 51 Block 1 Heredity and Phenotype 2.3 MULTIPLE ALLELES Multiple alleles refer to the existence of more than two forms of an allele in a species, which can give rise to a number of variations for a particular phenotype. Multiple alleles exist within a population and an individual possesses only two of its forms. Multiple alleles have been found in most populations including humans and have significant role in genetic stability of the population. Different allelic forms of a gene differ very minutely in their nucleotide sequence and thereby exhibit different levels of activity of their respective gene products. The phenotypes produced by multiple alleles may thus range from wild type (normal) to mutant. Most of the genes in populations of most organisms have multiple alleles. The ‘normal’ or ‘wild-type’ allele is thus not characterized by a single nucleotide sequence, rather it is a set of different nucleotide sequences, each of which is capable of carrying out the normal function of the gene. A classic example of multiple alleles is coat colours in rabits (Fig. 2.4). This phenotype is determined by a gene that has four alleles denoted differently i.e. allele C is for wild-type i.e. full colour, ch is for Himalayan characterized by white coat with black tips, cch is for chinchilla having mixed coat colour and white hair, and c stands for albino. The range of coat colours also exhibits a kind of gradation in the order of dominance of the concerned genes, as shown below- C>cch>ch>c Fig. 2.4: Expression of multiple alleles in coat colour of rabbits. According to this phenomenon, full colour C is dominant to all other coat colour alleles, chinchilla is dominant to Himalayan and albino, and Himalayan is dominant only to albino. This gradation has profound effect on the phenotypic and genotypic ratios of successive generations. The occurrence of homozygous dominant individuals (CC) is highest and this allele is called ‘wild 52 type’. Rest other alleles (cch, ch and c) are called mutants (Table 2.2). Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I Table 2.2: Different Genotypes and their respective Phenotypes for coat colour in rabbit. Genotypes Phenotypes ch h CC, Cc , Cc , Cc Full Colour (Wild type) cchcch, cchch, cchc Chinchilla chch, chc Himalayan cc Albino The inheritance pattern of multiple alleles of coat colour in rabbit is explained on the basis of two crosses between individuals of different phenotypes. When wild type homozygous full colour (CC) rabbit is crossed with homozygous recessive albino (cc), the phenotype of F1 heterozygous offspring (Cc) resembles dominant parent because allele C is dominant over c. The cross between two heterozygous (Cc) individuals yields coloured phenotype in 3:1 ratio in F2 generation. In another cross, when Himalayan (chch) individual is crossed with albino type (cc), the F1 heterozygous offspring (chc) show Himalayan phenotype. The cross between individuals of F1 generation again yields 3:1 phenotypic ratio in F2 generation (Fig. 2.5). Fig. 2.5: Cross showing inheritance of coat colour phenotype in rabbits. (a) Cross between coloured and albino, (b) Cross between Himalayan and albino. 2.3.1 ABO Blood Type Alleles in Humans Another common example of multiple alleles is ABO blood types in humans (Table 2.3). The blood groups in humans are classified as A, B, O, or AB, depending upon the three types of alleles IA, IB, and IO. Here, ‘I’ denotes an antigen ‘isoagglutinogen’ which is present on the surface of red blood cells. There are two types of oligosaccharides, either of which are attached to the common acceptor isoagglutinogen by the action of enzyme glycosyltransferase. This enzyme is the product of ABO gene having three alleles. Allele ‘IA’ encodes for A- glycosyltransferase which converts isoagglutinogen into A antigen, and allele ‘IB’ encodes for B- glycosyltransferase which converts isoagglutinogen into B antigen. Allele ‘IO’ 53 Block 1 Heredity and Phenotype does not encode any of these enzyme, instead produces a different protein, therefore no oligosaccharide component is attached to its corresponding isoagglutinogen and it is left unaltered. The blood group of an individual is determined by the type of allelic pair present. Both the alleles of blood types i.e. A and B, are codominant and express completely. Individuals having the genotype IA IA or IA IO have type A blood group and the ones having the genotype IB IB or IB IO have type B blood group. Heterozygous individuals IAIB have both A and B types of antigens therefore their blood group is designated as AB. People having homozygous allele combination IO IO lack either of the two antigens and their blood group is designated as O. Table 2.3: Genotypes and blood groups arising from different allelic combinations Genotype Blood Antigen on Antibodies in Can receive Can donate Type red blood plasma blood from blood to cells AO, AA I AI O , I AI A A A anti-B O and A A and AB BO, BB I BI O , I BI B B B anti-A O and B B and AB AB I AI B AB A and B neither O, A, B, and AB only AB OO I OI O O neither anti-A and O only O, A, B, and anti-B AB The ABO antigens are the most immunogenic of all other blood group antigens, therefore, ABO system of classification of blood group has foremost clinical significance. The agglutination reactions arising due to incompatibility of A, B and O antigens are most common cause of death following error or mismatch in blood transfusions (Fig. 2.6). Fig. 2.6: Agglutination reaction and subsequent hemolysis due to incompatible 54 blood transfusion. Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I The type of blood group is determined genetically and is, therefore, inherited by a child from his parents. Since the two alleles IA and IB are codominant, while IO represents a recessive allele, there are number of possibilities arising for blood type of children. The inheritance patterns can be followed by making probable parental combinations of alleles (Table 2.4). Table 2.4: Inheritance pattern of Blood Groups in Humans. 2.3.2 Rh Factor Alleles in Humans Rh Factor or Rhesus factor is second most clinically significant blood group system of ABO blood group system. It was discovered by Karl Landsteiner and AlexanderWiener in 1937 (published in 1940), long after the discovery of ABO system, when the two biologists carried out immunization experiments on rabbit using blood of rhesus monkey. They found that the antibodies produced after immunization, agglutinate the blood of monkey and also the blood of large number of human subjects. Rh incompatibility can be tested by reacting a blood sample with anti Rh serum and look for occurrence of agglutination as a positive response. An individual is either Rh + if his blood agglutinates, or is Rh- if there is no agglutination in such reaction. Rh factor is based upon the presence of certain antigens on the surface of RBCs. Until now, about 49 antigens have been identified, encoded by RHD and RHCE genes, making it genetically very complex. The D antigen encoded by RHD is said to be most immunogenic, therefore Rh + phenotype simply refers to the presence of D antigen while Rh- indicates its absence in the blood, usually due to deletion of the concerned gene. Alexander Wienner, discovered a number of Rh antigens and also proposed their nomenclature known as Rh–hr nomenclature. He postulated a theory for inheritance of Rh factor, later called Weiner’s theory. The theory suggests the presence of an Rh gene at a particular locus which has eight multiple alleles which produce this large array of Rh antigens. The five major ‘blood factors’ or antigens identified by Wienner were Rh0, rh’, rh”, hr’ and hr”, of which Rh0, rh’, rh” are encoded by gene R1 and hr’ and hr” are encoded by gene r. This system of nomenclature is not followed now and is replaced by the one developed by Ronald Fisher and R.R. Race. It is known as the Fisher- Race system or DCE nomenclature, and it recognizes five most common antigens D, C, c, E and e. The antigens C, c, and E, e are antithetical; antigen 55 Block 1 Heredity and Phenotype D lacks any antithetical antigen therefore ‘d’ is used to indicate absence of D antigen. In Weinner’s nomenclature, the antigens D, C and E correspond to Rh0, rh’, rh”, while c and e antigens correspond to hr’ and hr”. The antigen D is encoded by gene RHD and rest others are encoded by gene RHCE, located on a separate locus. The two genes constitute eight haplotypes -Dce, dce, DCe, dCe, DcE, dcE, DCE, and dCE, which are analogous to R0, r, R1, r′, R2, r″, Rz, and ry respectively in Weinner’s system of nomenclature. The Rh factor is clinically the second most important blood group system after ABO blood group and is essentially checked for incompatibility to avoid agglutination reactions after blood transfusion. It is also responsible for haemolytic disease in fetus and new born, a condition arising due to incompatibility between the fetal blood and maternal blood. When Rh- mother carries Rh+ fetus (gene for Rh+ blood group inherited by fetus from Rh+ father), she is immunized to Rh antigens due to exposure to these antigens. The first child is not affected, but during subsequent pregnancy, the second fetus may be exposed to maternal anti-Rh antibodies. These are anti-D IgG, which can cross the placenta, destruct the antigens on fetal RBCs, and cause hemolysis. The disease is called hemolytic disease of the newborn (HDN) or erythroblastosis fetalis, may range from mild to severe, even causing the death of fetus. The hemolytic disease of the newborn (Fig. 2.7), which is likely to occur due to RhD incompatibility, is prevented by injecting anti-RhDimmunoglobulin Rho (D) in mother at certain stages of pregnancy. IgG Rho (D) binds to fetal Rh antigens that enter the blood stream of mother and prevent the elicitation of primary antibody response. This preventive treatment reduces the risk of HDN in subsequent pregnancy. Fig. 2.7: Hemolytic disease (Erythroblastosis Fetalis) of the newborn and its prevention in Rh- mother 2.3.3 Incompatibility in Plants Incompatibility refers to the prevention of fertilization of male and female gametes in bisexual plants, despite the gametes are functional. Incompatibility 56 may be seen between the gametes of same species (intraspecific) or between Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I different species (interspecific). Intraspecific incompatibility, also known as self-incompatibility, may operate to prevent fertilization between the gametes of same plant or the gametes of different plants of same species. The mechanisms of self-incompatibility are different in case of pre-fertilization and post-fertilization barriers. The pre-fertilization involves pollen pistil interactions such as pollen-stigma interaction, pollen-style interaction and pollen-ovule interaction, in which the pollens may fail to germinate on stigma, if they germinate the growth of pollen tube may be inhibited or may fail to enter the ovule for gametic fusion. Self-incompatibility is controlled by a single gene (designated as S) with multiple alleles (Fig. 2.8). It was first discovered in tobacco (Nicotiana tabacum).The multiple alleles of gene S are represented by S1, S2, S3, S4 ……..Sn. All the alleles are codominant and either of the two alleles may be present in a plant. A plant with S1S2 genotype will produce pollens with either S1allele or S2 allele, which will be able to pollinate the pistil of all other genotypes except S1S2. In other words, even if single allele is common in both male and female parent plants, fertilization will not take place (Table 2.5). Table 2.5: Multiple alleles responsible for Self-incompatibility in plants. Male Female Genotype Compatibility Fertilization and Genotype Seed Production S1S2 S1S2 Incompatible No S1S3 S1S2 Incompatible No S3S4 S1S2 Compatible Yes S3S4 S2S5 Compatible Yes Fig. 2.8: Self-incompatibility in plants. 57 Block 1 Heredity and Phenotype SAQ 2 Read the following statements and write True (T) or False (F) against each: i) Most of genes in populations of most organisms have multiple alleles. ii) ABO antigens are the most immunogenic of all other blood group antigens. iii) Rh factor is the clinically most insignificant blood group system of ABO blood group system. iv) Self incompatibility is controlled by a double gene with multiple alleles. 2.4 GENE INTERACTIONS AND MODIFIED MENDELIAN RATIOS The gene interactions studied above are allelic or intragenic, i.e. different alleles of single gene interact and affect the expression of each other, and may also lead to the development of a new phenotype. However, there are interactions in which two or more genes located at different loci are responsible to produce a phenotype. The expression of these genes is influenced by each other and interactions among these genes may create new phenotypic combinations exhibiting modified Mendelian ratios. Such interactions are called non-allelic or inter-genic interactions. The different non-allelic interactions discussed here are complementary gene interaction, epistasis, supplementary gene interaction and duplicate genes. 2.4.1 Complementary Gene Interaction (9:7 Phenotypic Ratio) Complimentary genes are a pair of non-allelic genes that are together responsible to produce one phenotype. Both are dominant but neither is able to produce the phenotype alone. At least one dominant allele from both the gene pairs is required to produce the concerned phenotype. In the absence of any of the dominant alleles, i.e. when any of the recessive pairs is present, mutant phenotype is expressed. If parents heterozygous for both the genes are crossed, a phenotypic ratio of 9:7 is obtained in F2 generation. This interaction is seen in sweet pea (Lathyrus odoratus) in which two genes designated as C and P contribute in synthesis of anthocyanin to give purple colour to flowers (Fig. 2.9). The mutant phenotype in this case is white colour of flowers which appears due to non functioning of enzymes involved in biosynthesis of anthocyanin. If a homozygous pea plant with coloured flowers (CCPP) is crossed with homozygous recessive with white flowers (ccpp), the F1 generation have coloured flowers (CcPp). However, on selfing the F1 plants, the normal Mendelian dihybrid ratio (9:3:3:1) is not obtained, instead the interactions of 58 complementary nature between the two genes C and P genes gives a Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I modified phenotypic ratio (9:7). A similar cross is described in Figure-2.9 in which a cross between two homozygous parents with white flowers CCpp and ccPP yields F1 progeny with purple flowers (CcPp), which on selfing also exhibit complementary gene action. This cross infers that the anthocyanin pigment is biosynthesized only when a dominant allele from both the gene pairs is present, giving purple phenotype. Recessive pair of either of the two genes renders the enzymes of anthocyanin biosynthetic pathway non- functional and white flowers are produced. Fig. 2.9: Complementary Gene Interaction in Lathyrus odoratus. 2.4.2 Epistasis Epistasis is another kind of gene interaction in which one gene masks the expression of other non-allelic gene. The gene that shows the masking action is called epistatic gene while the one whose expression is masked is called a hypostatic gene. On the basis of the effect exerted on another gene, epistasis can be of two types- dominant and recessive epistasis. a) Dominant Epistasis:This type of gene interaction occurs when a dominant gene suppresses the expression of a gene at some other 59 Block 1 Heredity and Phenotype locus. For example, in Cucurbita pepo (summer squash), gene for white fruit colour is dominant and is designated as ‘W’ (Fig. 2.10). Another gene ‘Y’ controls the expression of yellow colour in fruit. The gene W exerts epistatic effect on the gene Y, therefore, the yellow colour is not expressed in fruits in presence of gene W. When both the genes (W and Y) are absent, green phenotype appears. The F2 phenotypic ratio in dominant epistasis is 12:3:1. Fig. 2.10: Dominant Epistasis in Cucurbita pepo. b) Recessive Epistasis- In this type of gene action, a recessive pair of alleles inhibits or masks the expression of a gene at another locus.The epistatic action is exerted by the homozygous recessive gene pair and its own expression by its dominant form occurs only in the presence of other dominant gene. Coat colour in mice is a common example of recessive epistasis. The coat colour in mice can be black, agouti or albino, and the phenotype is controlled by two pairs of genes- ‘A’ and ‘C’, both of which are non- allelic. The agouti coat colour in mice is expressed by gene ‘A’ only in presence of another dominant gene ‘C’. However, the recessive pair of alleles ‘cc’ masks the expression of the gene A, for both the genotypes AA and Aa. The black coat colour in mice is expressed by gene ‘C’ only in absence of dominant gene A. Recessive homozygous forms of both the gene pairs produce albino phenotype. The F2 phenotypic ratio in such a case is 9:3:4 (Fig. 2.11). 2.4.3 Supplementary Gene Interaction Supplementary gene interaction also occurs between two non-allelic genes, each of which is responsible for same trait. This type of gene interaction is very similar to recessive epistasis. In supplementary gene action, a dominant 60 gene is able to express its character, while another dominant gene, at different Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I locus, is able to express itself only in presence of the first one. For example, coat colour in mice is controlled by two pairs of genes- A and C. Gene C expresses black coat colour in mice. All the black mice consist of at least one dominant allele ‘C’ but no ‘A’. Whenever dominant gene ‘A’ is present along with ‘C’, agouti phenotype appears, i.e. A is expressed only in presence of C. Presence of either only dominant gene A or recessive forms of both (aa and cc) produce no colour and give albino phenotype. The F2 phenotypic ratio is same as in recessive epistasis i.e. 9:3:4 (Fig. 2.11). Fig. 2.11: Inheritance of coat colour in mice. 2.4.4 Duplicate Genes (Pseudoalleles) When two non-allelic pairs of genes are able to produce a phenotype, whether they are alone or together, are called duplicate genes. In such case, the mutant phenotype is produced by double homozygous recessive condition only. Example of duplicate genes is the presence of awn in the spikelet of rice, which is due to two dominant duplicate genes (A and B). The presence of awn is a dominant character and can be produced by any of the two genes. Therefore, the awn is absent in only those plants which are homozygous recessive (aabb). The F2 phenotypic ratio in such a cross is 15:1 (Fig. 2.12). 61 Block 1 Heredity and Phenotype Fig. 2.12: Duplicate Genes in rice. SAQ 3 Match Colum A with Colum B. Colum A Colum B i) Complementary Gene Interaction a) A recessive pair of alleles inhibit or maks the expression of a gene at another locus. ii) Dominant Epistasis b) Occurs between two non-allelic genes for same trait. iii) Recessive Epistasis c) Two non-allelic pairs of genes are able to produce a phonotype. iv) Supplementary Gene Interaction d) Dominant gene suppresses the expression of a gene. v) Duplicate genets e) Genes are a pair of non allelic genes. 2.5 LETHAL ALLELES In the previous section, you studied the various gene interactions resulting in the modification of the ratio of F, individuals. The genetic ratios are also affected by several other factors. One of them is a class of genes - lethal 62 genes, which you will study in this Section. Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I Genes may affect viability as well as visible traits of an organism. The living beings carrying certain genes are disadvantaged as they have impaired structural as well as, biochemical functioning. For example, Drosophila flies having white eyes and' vestigial wings have lower viability than their wild types. The detrimental physiological effects are apparently associated with the genes involved, that is, w and vg respectively. Some other genes have no effect on the appearance of a fly but do influence viability in some ways. Other Tay-Sachs disease genes have such serious effects that the organisms is unable to live. These (amaurotic idiocy): are called lethal genes and the alleles involved in the situation are termed as A genetic recessive lethal alleles. disorder that affects the central nervous If the lethal effect is dominant and immediate in expression, all individuals system. Its clinical carrying the gene will die and the gene will be lost. Some dominant lethals, symptoms are: however, have a delayed effect so that the organism lives for some time. cherry-red spot in eye Recessive Iethals present in the heterozygous condition have no effect but macula (the visible may come to expression when matings between carriers occurs. white portion of the eye); after 6-9 months We shall now take up an example for discussion, that clearly illustrates the rapid degeneration of functioning of these genes. In 1904, shortly after the rediscovery of Mendel's vision and motor principles, a French geneticist, Lucien Cuénot, while carrying out experimental skills; death at about crosses on coat colour in mice, found that a gene was not consistent with the 2-4 years of age. mendelian predictions. He observed from his experiments that the yellow body Huntington’s colour allele (Y) was dominant and agouti allele (y) was recessive. The disease (HD): A fatal crosses between two yellow mice (see Fig. 2.13) yielded approximately a 2:1 neurological disorder ratio of yellow to agouti mice rather than the expected ratio of 3: 1. Further, which is dominant. It when the yellow individuals (Yy) are crossed to the agouti (yy) Cuénot found is normally manifested after the that some agouti progeny are produced. He, therefore, concluded that yellow age of thirty, but has mice were heterozygous (Yy) and there were no yellow homozygotes (YY) in been reported to the progeny. Later, it was suggested that the yellow homozygotes were occur at all ages, HD actually lethal, and they died while still in the uterus. It was found that is characterised by 1 mental and physical approximately of the embryos from yellow by yellow crosses failed to 4 deterioration. There is develop. Therefore, the observed ratio of phenotypes differs from the expected progressive change in ratio, as they die very young - much before reaching the reproductive age. personality. As the disease progresses, the HD patients demonstrate twitching and uncontrollable muscle spasms. There is degeneration of Central Nervous System. (CNS) and loss of brain cells. This leads to fits of depression, insanity and suicide. At the time of death, the patients have lost about 25 per cent of their brain weight. Fig. 2.13: A cross between two yellow mice, yielding a 2:1 ratio in the offspring. 63  Block 1 Heredity and Phenotype Such lethals are by no means exceptional and must always be considered in populations of plants and animals. Many lethals produce no pronounced effect at all on the phenotype, but they may make their presence known by a decrease in the life span or the very elimination of the carrier. It has been estimated that each human carries, on the average, about six lethal alleles. How can an allele have a killing action? This perhaps may be the question arising in your mind. You may.remember that metabolism is the result of many interlocked biochemical pathways. A defect in just one step can upset several others. Just one defective step can alter the entire chemistry of the body. A lethal, by blocking a critical reaction, can interfere with normal embryological development of any organ, SAY heart. The death of embryo may then follow. Lethals can thus decrease the chances of survival by causing various kinds of abnormalities in development and physiology. Different lethals eliminate individuals at different stages of the life cycle. The complete lethal removes the carrier before the reproductive age so that those affected have no offspring, e.g., the allele for yellow coat colour in mice; in humans the recessive factor for Tay-Sachs disease which kills in infancy, In humans, the dominant factor for Huntington's disease, a fatal, deterioration of the nervous system, does not usually express itself before the age of 30. Such genetic determinants which can result in death but permit the carrier to live to reproductive age, are often grouped as sublethals. There is actually no sharp boundary during the life cycle at which lethals act. 2.6 PLEIOTROPY The action of a gene at the cellular level is unitary, that is, one gene one Metabolic fate of phenylalanine action. Sometimes the presence of a gene results in a broad spectrum of phenotypic changes, so that it appears that the gene has multiple action. normal pathway phenylalanine This phenomenon is called pleiotropy, and is found primarily in higher organisms where complex and interrelated developmental events occur. enzyme phenylalanine hydroxylase Many lethal alleles are pleiotropic. For example, the yellow coat colour in mice, just discussed, is an allele that affects more than one character, that is, converted to tyrosine it produces yellow colour of the coat in heterozygotes, and it also affects survival, causing lethality in homozygotes. Another example of multiple effects normal brain function is the gene affecting seed shape in garden peas; this gene also affects (a) starch grain morphology. In fact, many genes affect more than one trait. PKU – double recessive Mendel also noticed that genes causing the flower colours, like violet and pathway phenylalanine white, also influenced seed colour and caused the presence or absence of coloured areas on the leaves. This is due to pleiotropy as a single gene affects lacks enzyme phenylalanine more than one character. hydroxylase Pleiotropic traits also occur in humans. One such disease is phenylketonoria, converted to phenylpyruvic acid abbreviated as PKU. This occurs in individuals that are homozygous for a → urine defective, recessive allele. The diseased people lack the enzyme necessary for the metabolism of the amino acid phenylalanine. When normal and PKU mental retardation (b) individuals are compared, the level of phenylalanine is much higher in diseased group. In addition to this basic biochemical difference, a number of other features are seen in the untreated PKU patients, such as lower IQ, 64 similar head size and lighter hair. Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I 2.7 SEX-LIKED GENES In the crosses we have discussed so far, it has not mattered which parent carried a particular allele in question. Reciprocal crosses gave identical results. For example, in all the Mendel's monohybrid crosses, F1 and F2 were the same regardless of which P1 parent exhibited the recessive trait. This, however, is not the case in crosses involving genes located on chromosomes involved in the determination of sex. Such genes are said to be sex-linked. The first thorough study of the sex-linked gene was conducted by T.H. Morgan in 1910, when he was studying the inheritance of eye colour in Drosophila. The wild-type flies have brick red eye colour. Morgan crossed mutant white-eyed flies with red-eyed flies. He found that the result of a cross between a white eyed male (rII) and red-eyed female (RIIR) were different from those of a cross between white-eyed male. Both of these reciprocal crosses are illustrated in Fig. 2.14. (crosses a and b). Fig. 2.14: Crosses a and b 'illustrate inheritance of sex-linked genes in Drosophila. a) is a cross between red-eyed female and white-eyed male. And b) is the reciprocal cross of a). In the figure the long, rod- shaped structure (I) represents the X-chromosome and the inverted J- shaped structure (l) stands for the Y chromosome. Compare the phenotypic ratios of F2 generations of cross a with b. Is there any difference? Yes, there is a clear difference between the F2, individuals of the two crosses. The phenotypic ratios thus depend on whether the P, white-eyed parent was male and female. Morgan was able to correlate these observations 65  Block 1 Heredity and Phenotype with a difference found in chromosome composition between male and female Drosophila. It has four chromosomes and one of the chromosome varies between sexes (see Fig. 2.15). This chromosome pair (see XX or XY in the figure) is involved in sex determination mechanism and constitutes the sex chromosomes. The remaining chromosomes are called autosomes. The females possess two, rod-shaped homologs called the X chromosomes which are designated as XX. Males possess a single X chromosome and J-shaped Y chromosome, which are designated as XY. On the basis of this correlation, Morgan postulated that the gene for white eye is present on the X chromosome but is absent from the Y chromosome. Females thus have two available genes, one on each X chromosome while males have only one available gene on their single X-chromosome. 'This explanation supposes that the Y chromosome lacks homologous loci to these on the X chromosome. However, the X and Y chromosomes still behave as homologues in that they do partially synapse with each other and segregate into gametes during meiosis. Many species, including humans, possess an arrangement of sex chromosome as in Drosophila. Many sex-linked genes in humans have now been identified, e.g., the gene controlling one form of haemophilia and muscular dystrophy. We stop further discussion on this topic for the time being and shall resume it in an elaborated manner in Unit 4, that is, Sex Linkage and Dosage Compensation. 2.8 DEGREES OF GENE EXPRESSION In observing offsprings from a cross, we tend to think of a phenotype in terms of all or none of the phenomena. A trait is expressed or it is not - and we draw conclusions as to what are the types of genotypes based on that form of expression. While it is true that some phenotypes are always certain, such as, Fig. 2.15: Chromosomes in pea plants the genotype ss will produce always the wrinkled seeds. composition in Similarly, all of the Mendel’s genes and all blood group types show an Drosophila absolute arid clear cut pattern. However, for some genes, the expression is melanogaster. variable. 2.8.1 Penetrance Some individuals fail to slow particular trait, even though genetic analysis indicates that the controlling gene for that trait must be present in them. This aspect of gene action, that is the frequency with which a genotype is expressed in the phenotype is called Penetrance. For example, out of the eight individuals of a particular genotype, five express the diseased phenotype. The penetrance is 5/8 = 0.625 or 62.5%. A completely penetrant gene is always expressed; an incompletely penetrant gene may be expressed in some individuals, but not in others. Incomplete penetrance of a gene may cause a trait to skip a generation; that is, a dominant trait present in a given generation may skip the first generation but appear again in the second generation. Such a case is illustrated in Figure 2.16. It shows a human pedigree where unaffected individual II-4 is the daughter as well as the mother of an affected individual each. This indicates she has the genotype Aa, but because of incomplete penetration, does not 66 show the dominant phenotype. Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I Fig. 2.16: A pedigree illustrating the pattern of phenotypes with an incompletely penetrant dominant allele. 2.8.2 Expressivity Expressivity refers to the intensity or range of expression of a trait in different parts of the same individual or different individuals. This aspect of gene action differs from penetrance in that it describes the level of phenotypic expression, whereas penetrance refers to whether the phenotype is affected or not. Both penetrance and expressivity originate from variations in the degree to which a gene is manifested in the phenotype. These manifestations can be absent or be so slight as to pass unnoticed; in such individuals, a trait would be considered non-penetrant. However, when apparent in the phenotype, the same trait may vary in its effects from mild to severe, in which case the trait would be described as exhibiting not only variable penetrance, but variable expressivity as well. Let us consider the example of Drosophila. In this the recessive allele eyeless (e) when present in homozygous condition causes a reduction in the size of the compound eye. However, the extent to which the eye is reduced varies considerably from individual to individual. In some, only slight decrease in eye size occurs, while in others the eye may be completely absent. There are also cases in which the fly has one normal eye and the other eye drastically reduced in size. Phenotypic variation can also be observed in humans. Polydactyly exhibits variable penetrance, it is also characterised by differences in expressivity. In different individuals showing this trait, extra digits may be present on the hands or on the feet or both hands and feet. The source of this variation is partly genotypic and partly environmental. The genotype contains thousands of genes, and the actions of many of them are interrelated so as to modify one another's effects. For example, the level of expression of a trait is generally more similar among relatives than among unrelated individuals, provided that the relatives and unrelated individuals are raised in fairly similar environments. Such genes that have secondary effect on a trait are called modifier genes, and can sequentially influence the phenotype. The modifier genes can be seen in animals like house cat, where a 'dilute allele' reduces the intensity of pigmentation from black to grey. Another example of modifier genes is seen in D. melanogaster mutants when these are kept in laboratory culture for many years, sometimes they do not have as extreme a phenotype as was first observed. 67 Block 1 Heredity and Phenotype 2.9 SUMMARY Let us sum up what we have learnt in this unit: The dominance is a phenomenon of suppression of expression of one allele by another. The allele that is able to express its phenotype is called dominant, while the one whose expression is suppressed is called recessive. In heterozygous condition, i.e. when the dominant and recessive alleles occur together, if an intermediate phenotype appears due to blending of traits of both alleles, it is called incomplete dominance. Further in heterozygous condition if the phenotype of both dominant and recessive alleles express equally, the phenomenon is called co- dominance. Certain phenotypes are controlled by more than two alleles, known as multiple alleles, for example the range of coat colour phenotype in rabbits, ABO blood groups in humans and self- incompatibility in plants. There are some non-allelic gene interactions which may give rise to new phenotypes and are exemplified by modified mendelian ratios. These are complementary gene interaction, epistasis, supplementary gene interaction and duplicate genes. In complementary gene interaction, neither of the two dominant alleles of complimentary gene pair is able to produce the phenotype alone. At least one dominant allele from both the gene pairs is required to produce the concerned phenotype. The F2 phenotypic ratio in this case is 9:7. In another kind of gene interaction, one gene masks the expression of other non-allelic gene, known as epistasis. If the epistatic gene is dominant, it is called dominant epistasis, while if the masking action is due to a recessive gene, it is called recessive epistasis. The F2 phenotypic ratio in both the cases is 12:3:1 and 9:3:4 respectively. The gene interaction similar to recessive epistasis is supplementary gene action in which a dominant gene is able to express its character, while another non allelic dominant gene is able to express itself only in presence of the first one. The F2 phenotypic ratio in this case also is 12:3:1. A non-allelic gene interaction is observed in which the presence of any one dominant allele of the two gene pairs also produces a phenotype and the mutant phenotype appears only in double homozygous recessive condition. 2.10 TERMINAL QUESTIONS 1. Discuss the genetic basis of seed shape in peas. 2. State reason for appearance of pink flowers as an intermediate 68 phenotype in Mirabilis Jalapa. Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I 3. How is co-dominance different from incomplete dominance? 4. Explain the occurence of a range of coat colour phenotypes in rabbits. 5. Predict the blood group of a child if blood group of mother is ‘AB’ and that of father is ‘O’. 6. Explain the clinical significance of Rh antigens in human blood. 7. Describe the role of multiple alleles in self-incompatibility in plants. 8. Explain the complimentary gene action with example. 9. Explain the phenomenon of masking the expression of gene by another in epitasis. 10. Do you opine that the phenomena of recessive epistasis and supplementary gene interaction are same or different, explain. 11. Attribute the reason to obtain F2 phenotypic ratio 15:1 in appearance of awn character in rice. 2.11 ANSWERS Self Assessment Questions 1. i) recessive, ii) dominance, iii) co-dominance. 2. i) T, ii) T, iii) F, iv) F. 3. a) v, b) iv, c) i, d) ii, e) iii. Terminal Questions 1. Refer to Sub-Section 2.2.1. 2. Refer to Sub-Section 2.2.2. 3. Refer to Sub-Section 2.2.3. 4. Refer to Section 2.3. 5. Refer to Section 2.3.1 6. Refer to Sub-Section 2.3.2. 7. Refer to Sub-Section 2.3.3. 8. Refer to Sub-Section 2.4.1. 9. Refer to Sub-Section 2.4.2. 10. Refer to Sub-Section 2.4.3. 11. Refer to Sub-Section 2.4.4. 69 Block 1 Heredity and Phenotype FURTHER READINGS 1. Principles of Genetics by Gardner, Simmons, Snustad, 8thedition – John Wiley and Sons, Inc., 2003. 2. Genetics: a Conceptual Approach, 3rdedition, Peter J. Russell. Pub: WH Freeman & Co. 3. Genetics: Principles and Analysis, 4thedition. D.L. Hartl, D.W. Jones. Pub: Jones and Barlett Publishers 4. Genetics, 9threvised multicolor edition. P.S. Verma & V.K. Agarwal. Pub: S. Chand & Co. Acknowledgement of Figures Fig. 2.1: http://legacy.biotechlearn.org.nz/layout/set/lightbox/themes/ mendel_and_inheritance/mendel_s_principles_of_inheritance Fig. 2.3: https://biologywise.com/codominance-explained-with-examples Fig. 2.4: https://courses.lumenlearning.com/bio1/chapter/reading-multiple- alleles/ Fig. 2.5: http://www.eplantscience.com/index/genetics/multiple_alleles_ based_on_classical_concept_of_allelomorphism/skin_colour _in_rodents.php Fig. 2.6: https://courses.lumenlearning.com/microbiology/chapter/ hypersensitivities/ Fig. 2.7: https://courses.lumenlearning.com/microbiology/chapter/ hypersensitivities/ Fig. 2.9: http://www.biologydiscussion.com/genetics/gene-interactions/gene- interactions- allelic-and-non-allelic-cell-biology/38795 Fig. 2.10: http://www.biologydiscussion.com/genetics/gene-interactions/ gene- interactions -allelic-and-non-allelic-cell-biology/38795 Fig. 2.12: http://www.biologydiscussion.com/genetics/gene-interactions/top-6- types-of-epistasis -gene-interaction/37818 70