- 1 Deviation from Mendelian Ratio and Apparent Contradiction to the Law of Independent Assortment
- 1.1 1. Incompletely Dominant or Co-dominant Alleles Modifying the Ratio:
- 1.2 2. Modification of Phenotypic Ratio When of the Two Pairs of Alleles, One Pair only Show Incomplete Dominance:
- 1.3 3. Two Pairs of Alleles Interact to give a New Phenotype without Modifying the F2 Phenotypic Ratio in Dihybrid Cross:
- 1.4 4. Multiple Alleles and Inheritance of Blood Groups:
- 1.5 5. Pleiotropy:
Evolution is one of the Biology Topics that has been debated and studied for centuries, exploring the process by which species change over time.
Deviation from Mendelian Ratio and Apparent Contradiction to the Law of Independent Assortment
Sometimes genes even not being allelic by nature may interact to modulate the expression of character. This is known as gene interaction or inter-allelic interaction. For such interactions, the results from hybridization may be affected. In the case of dihybrid experiments, the usual Mendelian F2 phenotypic ratio (9 : 3 : 3 : 1) is found to be modified due to gene interaction of various types. Such modification of the typical F2 phenotypic ratio may appear as a contradiction to an independent assortment of genes. But intense scrutiny of the result of the dihybrid crosses indicates that different alleles of non-allelic genes segregate independently as suggested by Mendel.
1. Incompletely Dominant or Co-dominant Alleles Modifying the Ratio:
Mating of the heterozygotes for two different characters that are controlled by either co-dominant or incompletely dominant genes may give progeny of 8 different phenotypic combinations in which case the phenotypic ratio will be changed to 1 : 2 : 1 : 2 : 4 : 2 : 1 : 2 : 1. With an arbitrary example this type of modification may be illustrated.
Let gene A determines the phenotype m and its allele a determines the phenotype n. A is incompletely dominant over a and genotype Aa gives phenotype m’. On the other hand, let the B determines the phenotype x and its allele b gives the phenotype y; but the heterozygote Bb gives the feature x’, because B is incompletely dominant over b. On the basis of the above-noted conditions, the phenotype for the AABB genotype is mx and that of aabb is ny. On the other hand in heterozygous condition, AaBb genotype gives the expression as m’x’. Therefore, from the parental AABB and aabb organisms, the F2 progeny may be developed as indicated in the following diagram.
2. Modification of Phenotypic Ratio When of the Two Pairs of Alleles, One Pair only Show Incomplete Dominance:
In the case of two pairs of alleles, if one pair exhibits incomplete dominance and the other pair exhibits complete dominance and recessiveness, the F2 phenotypic ratio is modified as indicated in the following diagram. In the present example, A is completely dominant over a and produces m phenotype. In homozygous conditions, aa produces n expression. On the other hand, gene B is incompletely dominant over b, showing x, x’, and y phenotypes. In such case, heterozygote crossing may give the phenotypes as indicated on Next Page.
Let, two pairs of alleles are A, a and B, b. Out of these allelic pairs A shows complete dominance over a; while B is incompletely dominant over b. A being expressed gives a phenotype m and aa condition develops n phenotype; while BB condition gives phenotype x, Bb shows the phenotype x’, and bb exhibits y phenotype. In this condition, a dihybrid cross between AABB and aabb gives AaBb with mx’ phenotype. The cross between two mx’ individuals may give the phenotypes as indicated in the above diagram and their ratio shows deviation from the typical Mendelian ratio. A cross between heterozygous horned roan bulls and the heterozygous homed roan cow may develop a situation as indicated above.
In cattle horned and polled conditions are controlled by alleles with clear dominant effect. On the other hand coat color in cattle may be red, roan, and white because of two alleles having incompletely dominant effects. Suppose the horned condition is determined by the gene H and its recessive allele h determines polled condition in homozygous condition, whereas the red coat colour is determined by R which shows incomplete dominance over its allele r. In such conditions, Rr produces a roan feature which is the mosaic of red and white coats.
3. Two Pairs of Alleles Interact to give a New Phenotype without Modifying the F2 Phenotypic Ratio in Dihybrid Cross:
There are four types of comb expressions in hen and these are rose, walnut, single, and pea. It is found that due to the interaction of two pairs of alleles, these phenotypic variations come into expression. Let, the gene for the rose feature is R and that for the pea feature be P. Both the genes are dominant over their recessive forms of allele r and p respectively. When both R and P are present together walnut becomes the expression and a homozygous recessive condition for both the genes gives a single comb.
Therefore, the phenotypes for different genotypes for comb features may be indicated in the following way-
Comb features in fowl and corresponding Genotypes:
When mating occurs between pure breeding rose comb cock and pea comb hen, the progeny appear to be all with a walnut comb. Walnut x walnut results in four phenotypes walnut, rose, pea, and single in the ratio 9 : 3 : 3 : 1.
In a gene interaction when one gene suppresses the other non-allelic gene, the phenomenon is called epistasis and the gene is called an epistatic gene. The gene which is suppressed is called the hypostatic gene. In the case of epistasis F2 phenotypic ratio of the dihybrid cross is modified. Different types of epistasis and their impact on modifying the F2 phenotypic ratio may be discussed as under.
When a recessive gene in a homozygous condition suppresses the expression of another gene, it is called recessive epistasis. Let one gene has two alleles A and a. Another pair of alleles B and b together with A and control the expression of a character. The two pairs of alleles have an epistatic relationship when at homozygous condition aa suppresses the expression of the B or b gene. Therefore, similar expressions will come from aaB- and aabb genotypes.
In rats and other rodents in the expression of coat colour, this type of interaction may be encountered. The normal coat colour of a rat is grey. This feature is also known as agouti and for the expression of agouti feature presence of two different dominant genes is required. Let two dominant genes for which agouti coat colour may be developed by A and C. In this case, C determines the colour development, and A contributes to the agouti pattern. Agouti pattern indicates the appearance of black and yellow bands along the fur. If in a rat instead of C, c remains present in homozygous conditions, then no colour development will be possible along the fur, and expression of the A gene cannot occur.
On the other hand, if aa condition remains present with the C gene, fur shows black colouration without the development of an agouti pattern. In the case of A_cc and aacc coat colour becomes white, i.e., the rats with such genotypes become albino. Gene interaction for the coat colour in rats altogether gives three expressions namely agouti, black, and albino.
In consideration of two different genes as stated above, when a homozygous agouti is crossed with a homozygous albino rat, all the F1 progeny appear to be agouti in phenotype. F1 hybrid agouti male and female when are allowed to mate agouti, black and albino progeny appear in the proportion 9 : 3 : 4. Therefore, the classical 9 : 3 : 3 : 1 phenotype ratio is changed to 9 : 3 : 4 on account of recessive epistasis.
Duplicate Recessive Epistasis:
Two non-allelic genes when in homozygous recessive condition prevent the expression of either of the dominant genes, the event is known as duplicate recessive epistasis.
Suppose two non-allelic genes A and B together determine a particular character. Their recessive form of alleles are ‘a’ and ‘b’ and either of these two recessive genes in homozygous condition may suppress the expression of gene A or gene B. Hence if A-B- combination gives a normal phenotype but aaB- or A-bb gives an abnormal phenotype.
In man speaking power and audibility appear to be one of these types of interaction. With relation to speaking power and hearing, the normal condition comes in the presence of the two dominant genes, say A and B. According to the principle of duplicate recessive epistasis, either of the recessive alleles (i.e., a or b) of these two genes (i.e., A and B) in the homozygous state may suppress A or B genes producing deaf and dumb expressions. In such epistasis, F2 phenotypic ratio becomes 9 : 7.
When a dominant gene prevents another non-allelic gene from expression, it is known as dominant epistasis. In the case of dominant epistasis F2 phenotypic ratio is changed to 12 : 3 : 1.
In summer squash fruit colour may be white or yellow or green. The expression of these features appears to be the outcome of dominant epistasis. Suppose, the gene determining the white fruit colour is W and its allele w is recessive to W. On the other hand, the yellow fruit colour is due to the gene Y. Its recessive allele y in homozygous condition gives green colour to the fruit.
However, in this case, W may suppress the expression of Y and therefore, Y may only be expressed in the case ww gene combination. The genotype W-Y- or W-yy only gives white colouration. Because of this, the cross between WwYy and WwYy may give white, yellow, and green in a ratio 12 : 3 : 1.
Duplicate Dominant Epistasis:
When two dominant genes prevent each other from being expressed, it is known as duplicate dominant epistasis. Suppose, two dominant genes A and B exhibit epistatic influence over each other. Therefore, any genotype carrying the A or B gene will exhibit the same phenotypic expression. A different phenotype will come from aabb genotype. In case of duplicate dominant epistasis F2 phenotypic ratio will be 15 : 1.
In the shepherd’s purse plant, two types of seed capsules may be developed and these are triangular and top. Suppose, two dominant genes A and B with duplicate dominant epistatic effects determine the expression of fruit shape in this plant and therefore. A-B-, A-bb, and aa-B- all give the same phenotype i.e., triangular feature. The top feature comes from the genotype aabb.
Duplicate Interaction or Supplementary Gene Action:
When two dominant genes with co-action determine a phenotype, it is known as duplicate interaction. This effect is also called supplementary gene action. In this interaction, only one of the two dominant genes being present gives a familiar but different phenotype. In the absence of the dominant genes i.e., in recessive homozygous condition another phenotype appears. This type of gene interaction modifies the F2 phenotypic ratio to 9 : 6 : 1.
In summer squash the shape of the fruit may be of three types namely disc, sphere, and oblong. Suppose, in determining these features there are two allelic gene pairs A/a and B/b. However, because of duplicate interaction A-B- genotype gives disc-shaped fruit, aaB- and A-bb genotypes produce spherical fruit, but aabb gives oblong fruit. Therefore, modification of the F2 phenotypic ratio by duplicate gene interaction may be represented by the following diagram.
4. Multiple Alleles and Inheritance of Blood Groups:
Multiple alleles is a type of non-Mendelian inheritance pattern that involves more than just the typical two alleles that usually code for a particular characteristic in a species. Multiple alleles mean there are more than two phenotypes available depending on the dominant or recessive alleles that are available in the trait and the dominant pattern the individual alleles follow when combined together. Alleles are alternate forms of a gene. In Mendel’s concept, it would mean that each gene had two alternative forms or allelomorphs, one being dominant and the other recessive. In a diploid organism, a particular gene pair contains only two alleles at a time occupying the same locus in a couple of homologous chromosomes.
In Mendel’s experiments, there were two possible kinds of alleles in a gene pair, i.e., Yellow or green (Y, y) or smooth or wrinkled (S, s), or tall or dwarf (T, t), etc. But actually, the presence of more than two alleles of a gene is quite possible. The grouping of all the different possible alleles that may be present in a gene is defined as a system of multiple alleles. More than two alleles on the same locus are called multiple alleles. The mutation of a gene at a particular locus in a chromosome produces a variant called an allele. Such mutations may occur further in the individuals and their progeny and produce several variant forms. Alternative forms of a gene are very often available and alternative forms of a gene are called alleles. When a number of alleles become more than two, they are called multiple alleles.
In Drosophila wings are normally long. They occured two mutations at the same locus in different flies, one causing vestigial (reduced) wings and the other mutation causing antlered (less developed) wings. Both vestigial and antlered are alleles of the same normal gene and also of each other and are recessive to the normal gene. Thus wings of Drosophila is the example of multiple alleles. Two human examples of multiple allele genes are the gene of the ABO blood group system and the human leukocyte-associated antigen (HLA) genes.
ABO Blood Group in Humans:
In humans, people may be grouped into four categories as A, B, AB, and O in consideration of their blood features. This blood group was discovered by Karl Landsteiner in 1900 and for this discovery, he was awarded with Nobel Prize in 1930.
On the basis of the presence and absence of antigen on the surface of RBC four types of blood may be categorized. However, the blood types have characteristic hostile relation that is determined by antigen-antibody interaction between the blood types. The RBC of the A blood type contains A antigen on the surface, while the RBC of the B blood type contains B antigen on the surface. The AB blood type contains both A and B antigens on the RBC surface and the RBC of O blood type contains no antigen on the surface of RBC. This difference in the blood type is also associated with antibodies in the blood plasma of different blood types. The plasma of A blood contains anti-B antibodies, the B blood contains anti-A antibodies, the O blood contains both anti-A and anti-B antibodies and the AB blood does not contain any antibodies in blood plasma.
On the basis of the above features, the four blood types may be figured in the following manner. In analyzing the genetics of this blood group it has been observed that four phenotypes of the ABO blood group are determined by three alleles and they are designated as IA, IB, and i. Among these three genes, IA and IB are codominant alleles and i is recessive to both IA and IB. A blood group is developed when the gene combination will be IAIA or IAi and B blood group is developed in the condition IBIB or IBi. But homozygous ii condition helps in the development of the O blood type. On the other hand, IAIB genotype leads to the development of AB blood type, because IA and IB are codominant alleles. The genotypes of the four blood types may be indicated in the following on the next page.
Because of antigen antibody-related features different blood group samples show antigen-antibody reactions which become a threat to human life. If blood from an A group individual is transfused to a B group individual the A blood in B individual due to antigen-antibody reaction exhibits agglutination reaction when RBCs of A blood are aggregated together being bound with Anti A antibodies in the plasma of B individual. Similarly, if B blood is given to A individual due to antigen-antibody reaction agglutination reaction occurs in the B blood. This leads to the death of the recipient. The O individual cannot receive blood from any of the other types of blood, because the blood of the O individual contains both anti-A and anti-B antibodies in blood plasma. On the other hand, the AB individual can receive blood from any other group of blood because the AB blood group individual does not contain any antibody in the blood plasma.
Genotypes of Different Blood Groups of Humans:
|A||IAIA or IAi|
|B||IBIB or IBi|
ABO Blood Types and their Reactions as Occur during Blood Transfusion:
ABO blood group individuals in the population show about ten marriage relationships at random as indicated below. These mating types on the basis of the probable genotypes of the mating partners may produce the progeny as indicated below. The genotypes of the mating partners determine the phenotypes of the progeny and therefore, different mating types as indicated in the table indicate the types of offspring produced. On the basis of the progeny types produced from a couple, their blood type and the corresponding genotypes may be predicted. Hence, in case of disputes related to parenthood, ABO blood type analysis may come to use to some extent.
Marriage Relationship among ABO Blood Group Individuals:
In Bombay, India, an individual was discovered to have an interesting blood type that reacted to other blood types in a way that had not been seen before. The serum from this individual contained antibodies that reacted with all RBCs from normal ABO phenotypes. The individual’s RBCs appeared to lack all of the ABO blood group antigens plus an additional antigen that was previously unknown.
In the human population rarely some individuals are available that contain O blood but they are not typically like O individuals. Instead of having genotype ii, such an individual may contain IA or IB gene in the genotype. During the production of progeny, they may produce either A or B-type progeny being mated with typical O-group individuals. This type of O blood is known as the Bombay phenotype. Because this type of blood type was first discovered in the Marathi people of Bombay, this blood is named as Bombay phenotype.
To find out the reason behind the development of the Bombay phenotype, scientists could reveal that for the formation of A or B antigen, a person needs the production of H substance in the blood. This H substance is converted into A or B antigen in the presence of the IA or IB gene. Formation of H substance occurs in the presence of a dominant gene H under whose influence a precursor may be converted into H substance. This H substance is the immediate precursor of A or B antigen.
Typically in the O group individual H substance may be produced but the typical O individual lack a gene for the conversion of H into either A or B antigen. The Bombay phenotype individual contains no H gene and the individual is recessive homozygous for a mutation of the H gene, denoted as h. Therefore, such a person is hh by genotype. In the Bombay type, individual H substance cannot be produced in spite of a person containing the IA or IB gene. This is a case of recessive epistasis.
The pedigree shown indicates a case of Bombay phenotype that is developed from A and AB parents. Normally A and AB parents in no case can develop a progeny of O type because one progeny with ii genotypes cannot come from the parents with A and AB blood group. A father having a genotype IAIAHh and a mother with AB phenotype having genotype IAIBHh may produce the progeny with O blood type (Bombay phenotype) with a genotype IAIBhh or IAIAhh. In such a case the gametic contribution for father another will be IAh and IBh or IAh respectively.
The mating types relating to ABO blood types and probable genotypes of the progeny:
MN Blood Group:
MN blood group is another series of blood groups in humans. Landsteiner and Levine in 1927 discovered this blood group system in man and divided human populations into three groups as M, MN, and N. The gene for this MN series was symbolized as L and alleles as LM and LN in honour of its discoverer.
In the MN series of blood groups, human blood serum does not contain any antibodies which may cause agglutination. But if human blood is injected into a rabbit, it produces specific antibodies and agglutination occurs. When M group blood is injected in rabbits, it will produce antibodies in serum called anti-M serum that causes agglutination of M and MN but not of N. Similarly, N group blood produces antibodies in serum called anti-N serum that agglutinates N and MN but not M. Since LM and LN alleles are codominant, heterozygote LMLN produces MN blood group. Different MN blood groups and their genotypes, antigens, and antisera are shown in the following table:
Inheritance of MN Blood Group:
The gene L and its alleles are inherited by the crosses of different mating combinations of MN blood groups and their resulting progenies and improbable blood groups are shown in the following table:
Rh Blood Group:
In 1940, Landsteiner and Wiener discovered Rh factor from rabbits immunized with the blood of rhesus monkeys (Macacus rhesus). Levine and others later found this blood type in humans. This Rh factor, first detected in the RBC of Rhesus monkeys, was initially thought to be caused by a gene with only two alleles, R and r. Further studies showed that the Rh factor was genetically quite complex. Correlated with genetic studies, Wiener and others indicated the existence of atleast eight different Rh alleles, namely: r, r’, r”, ry, R0, R1, R2, Rz.
Basically, there are two Rh blood group types; Rh positive (Rhf) and negative (Rh-), on the basis of incompatibility. A serious disease called erythroblastosis fetalis occurs when the father is Rh+ and the mother is Rfr in such cases, all the children born will be Rh+, if the father is homozygous (RR) and if the father is heterozygous (Rr), half the children will be Rh positive. If Rh negative mother carries an Rh-positive fetus in the first case of pregnancy, no problem occurs. But in subsequent pregnancy antibody concentration in the mother’s blood will increase and that may cause the death of the fetus due to hemolytic jaundice and anemia this disease is called erythroblastosis fetalis. It is noteworthy that in the human population, 15% of individuals appear Rh -ve. While the rest represents Rh +ve.
Mechanism of Erythroblastosis Fetalis:
The following six incidences occur one after another serially:
- An Rh+ man and an Rh- woman have an Rh+ child.
- Rh+ blood cells escape from fetal circulation.
- Stimulation of maternal production of antibodies.
- These antibodies enter fetal circulation.
- Cause destruction of blood cells (RBC).
- Production of hemolytic disease as Anemia, Icterus gravis, and Hydrops fetalis.
Fisher, Race, Sanger, and other workers (1968) have tried to replace Rh nomenclature, with one, based on three closely associated gene pairs, D, C, and E. According to their system, each Rh gene is a combination of alleles at each of these gene pairs, e.g., r = dee, rz = DCE. Therefore, alleles r = dee, r’ = dCe, r” = dcE, ry = dCE, R° = Dee, Rz = DCE etc. and Genotypes R1r = DCe/dce, R1R2 = DCe/DcE etc.
A picture of Rh+ve and Rh-ve individuals with their genotypes may be given in the following way:
Multiple Allelic Series for coat colour in Rabbit:
For coat colour variation in rabbits, as many as four alleles could be detected for the development of four different coat colour namely Agouti, Chinchilla, Himalayan, and Albino. The Agouti or full colour is the colour pattern in which the coat colour appears as grey. The Chinchilla appears as a spotted coat over the grey background, whereas in the Himalayan pattern, only the extremities of the body become black in colour. The Albino condition results in a completely white body.
A Cross between Two Hybrid Chinchilla Rabbits:
It has been observed that the normal coat colour of rabbits is developed due to a gene called C, Chinchilla is due to Cch, Himalayan is due to Ch and albino is due to c. The genes are allelic in nature with a relationship as indicated below C> Cch > Ch > c. Therefore, the presence of C, Cch, and Ch even in heterozygous conditions contributes to Agouti, Chinchilla, and Himalayan coat colour respectively. When a Chinchilla rabbit is crossed with a Himalayan rabbit all the Fj progeny will appear as hybrid indicating the dominance of the gene of Chinchilla over that of Himalayan therefore, when the hybrids are allowed to interbreed Chinchilla and Himalayan Rabbit in 3 : 1 ratio.
Pleiotropy is a genetic phenomenon when a single gene has more than one phenotypic effect. More simply, pleiotropy means one gene and many effects. Such genes are called pleiotropic genes, which in addition to their main effect, may also act as modifiers for another but entirely different gene. A Mendelian disorder with several symptoms, different subsets of which may occur in different individuals, is termed pleiotropic. Pleiotropism is valuable in understanding relations between different developmental processes. Pleiotropy occurs when a single protein affects different parts of the body or participates in more than one type of biochemical reaction.
Examples of Pleiotropy:
- Dobzhansky (1927) has demonstrated that a gene for white eyes in Drosophila may affect the shape of sperm storage organs in females as well as other structures.
- In Drosophila Hersh has shown that a number of facets in Bar-eyed individuals may be significantly altered by the presence of other genes that also affect bristles, eyes, and wings.
- In humans, an autosomal dominant pleiotropic disease, Marfan Syndrome, the genetic defect affects the elastic connective tissue protein called fibrillin and this protein product of this pleiotropic gene also affects the eye lens, which may dislocate the aorta and limb bones and fingers. Limbs would be long and fingers become spindle. The most serious symptom is a life-threatening weakening in the aorta wall which sometimes may suddenly burst.
- Another autosomal dominant, Pleiotropic disease, in humans, Porphyria, for example, had effects on the Royal families of Europe, particularly King George III of England. At age 50, he first felt abdominal pain and constipation, followed by weak limbs, fever, fast pulse, and dark red urine. Next nervous system symptoms began, including insomnia, headaches, visual problems, restlessness, delirium, convulsions, and stupor.
- Parliament and Court were convinced that the king was mad. But he mysteriously recovered and again relapsed 13 years later and thereafter 3 years later, finally an attack in 1811 placed George in a prolonged stupor.
Types of Pleiotropy:
The effects of genes in pleiotropy may be of several categories as indicated in the following table:
|1. Artefactual Pleiotropy||In the genome where genes are closely located there this type of pleiotropy is found.||The claret allele of fruity fly.|
|2. Secondary Pleiotropy||When for simple bioorganic activity many phenotypes come.||The mutation for Phenylketonuria in man.|
|3. Adoptive Pleiotropy||When the same gene product is used in different tissues for different purposes.||The gene product for lysosome and α-lactalbumin.|
|4. Persimonious Pleiotropy||The FDY gene too a B-sub unit of a protein in C. elegans.||When an enzyme for the same chemical reaction acts in various ways.|
|5. Opportunistic Pleiotropy||When a gene besides its primary action does some other activity secondarily.||SISB gene of fruit fly.|
|6. Combinatorial Pleiotropy||When the product of a gene functions as an associate of another substance.||Unc in C. elegans helps the formation of different cells.|
|7. Unifying Pleiotropy||When one gene in combination act for one biological function.||Cha.1 unc-17|