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LECTURE NOTES Course: GBT 201; INTRODUCTORY GENETICS (3 Credits /Compulsory) Course Duration : 15hrs Teaching and 45hrs Practical Lecturer: BELLO, Omolaran Bashir Ph.D, M.Sc. (Ilorin), B.Sc. (Ibadan), OND (Computer Studies) Course: PST 204 Plant Morphology (2 Credits /Compulsory) Course Duration: 15hrs Teaching and 45hrs Practical E-mail : [email protected], obbello [email protected] [email protected] Office Location: Department of Biological Sciences Consultation Hours; 2.30-4.00 pm Monday-Thursdays. Course Content 1. The Principles of Genetics 2. Mitosis and Meiosis 3. Mendelian Laws 4. Gene Interaction 5. Multiple Factors 6. Multiple alleles 7. Variation in gene expression 8. Linkage and chromosome mapping 9. Gene structure and function 10. Nucleic acid and coding 11. Mutation 12. Introduction to population genetics Hardy-Weinberg Law Evolutionary Processes and factors 1. Introductory Genetics Genetics is the branch of biology which studies the origin of biological variations , organizations of variations and how these are transmitted from one generation to another or from parents to offspring. The transmission of genetic materials from parents to offspring is known as heredity. Variation is the difference which may distinguish one from the other. Types of Variation 1. Heritable Variation: exists in the parents and passed on to the offspring. In sexual reproducing organisms, sperm, pollen grains , egg and ovum constitute the germ line in containing attributes of parents that are passed on to the offspring e.g. diabetes milletus (although can be controlled by the admission of insulin) is heritable. Others examples include height, size, color, texture etc. 2. Non-heritable variation: are developmental errors which cannot be passed on to the offspring from their parent e.g. post-natal accident such as blindness, or amputation of part of the body. Partial heritable variations are heritable or non-heritable and are acquired from d environment. a. Morphological Variation .i.e. physical appearance induced by the environment .e.g. albinism is induced in plants by raising them in the dark because it prevents chlorophyll formation. The situation is reserved once such plants are allowed to receive rays of sun. b. Muscle Development by weightlifters, wrestlers, boxers. c. Differences between the yolk of poultry raised in battery cages and those raised in free range. These raised in free range have more carotenoid. (Color pigment in plant organism). d. Behavioral Tendencies which may be peculiar to group people e.g. cultural traits and mannerism which are passed on to the offspring, also known as acquired characteristics. 3. Partly heritable and partly cultural includes body movement, Characteristics of the female which differ from that of the male. This difference is partly due to the muscle structure of the female and distribution of their sexual organs. However much of movement is still learnt from others .i.e. learning from pairs. Principles of Genetics a..The site where genes work is the cell, each cells may have different functions b.. Each cell function within an organism is determined by the genetic information encoded in DNA. c.. In Eukaryotes (Organisms whose cells contain a nucleus) DNA reside within membrane bound structure in the cell. These structures include the nucleus, the energy producing mitochondria and in plants, the chloroplasts (structure where photosynthesis takes place). d.. In Prokaryotes(One cell Organism) and bacteria that lack internal membrane bound structure, DNA floats freely within the cell body. Importance of Genetics The modern science of genetics influences many aspects of daily life from the food we eat to how we identify criminals or treat diseases 1. In agriculture, genetic advances enable scientists to alter a plant or animal to make it more useful. For instance, some food crops such as oranges, potatoes, Wheat and rice have been genetically altered to withstand insect, pest and diseases resulting into higher crop yield. Tomatoes and apples have being modified to resist discoloration and their way to the market. Their genetic make-up of cattle (cows) have been modified to increase their milk production and cattle raised for beef have been altered so that they grow faster. 2. Genetic technologies have also helped to convict criminals, DNA recovered from the semen (sperm), blood, skin cells or hair found at a criminal scene can be analyzed in the laboratory and compared with the DNA of the suspect. DNA match can also be used in courtroom as evidence connecting a person to a crime or ownership of a child. 3. In medicine, scientists can generally alter bacteria so that they mass produce specific proteins such as insulin used by diabetes patient or human growth hormone used by children who suffer from growth disorder 4. In gene therapy, scientists try to cure disease by replacing malfunctioning genes with healthy ones e.g. cancer, fibrosis, e.t.c Genetically engineered vaccines being tested for possible use against the Human Immunodeficiency Virus (HIV). The virus that causes Acquired Immunodeficiency Syndrome (AIDS). 5. Human Genome Project; Scientists have developed detailed maps that identified the chromosomal locations of the estimated 20,000-25,000 human genes. The data bases help scientists study previously unknown genes as well as many genes all at once to examine how gene activity can cause disease. The scientists expected that their project would lead to the development of new drugs targeted to specific disorders. 1. 1 Cell division This the replication of cells for the growth and development the reproduction during because of the cell of organism could not grow or function properly if the genetic information encoded in the DNA was not passed from cell to cell. DNA is packed into structures called chromosomes within a cell. Every chromosome in cell contains many genes, and each gene is located at a particular site, or locus on the chromosomes. Chromosomes vary in size and shape and usually occur in matched pairs called homologues. The number of homologues chromosomes in cell depends upon the organism e.g. human body contains 23 pairs of chromosomes, maize: 20, Fruitfly: 4, onion: 16 e.t.c. Organisms use two types of cell division to ensure that DNA is passed down from cell to cell during reprod uction. Asexual reproduction is by mitosis, a cell doubles its DNA before dividing into cells and distributing the DNA evenly to each resulting cell. Organism that reproduces sexually is by meiosis. The garment or egg and sperm (germline) The chromosome in a gamete cell are reduced by half. During sexual reproduction, an egg and sperm unite to form a zygote in which the full number of chromosome is restored. 1.2 Cell cycle This is entire sequence of events happening from the end of one nuclear division to the beginning of the next. It is divided into four stages namely G,S and G2 (Interphase) and M (mitosis and cytokinesis) G1:After the N phase of previous cell cycle, the daughter cells begins G1 of inter-phase of new cell cycle. It is the resting stage and involves in synthesis of RNA and proteins. S1: Period of DNA synthesis G2: Period between the end of DNA synthesis and the beginning of the prophase M:Is the period of chromosome division. 1. 2. 3. 4. 2.0 MITOSIS This is conventionally divided into four stages Prophase Metaphase Anaphase Telophase Overlapping with the latter stages of mitosis, cytokinesis completes the mitotic phase. Interphase which is a resting stage is the centre of intercellular activities such as energy transformation, synthesis of protein, oil, starch e.t.c and also synthesis of genetic material and duplication. Mitosis can be defined as process by which the nucleus divides into two daughter nuclei each with equivalent chromosome complement. DIAGRAMS 1 Prophase The chromatic fibres become more tightly coiled condensing into discrete chromosome Observable with light microscope. The nucleoli disappear. Each duplicate chromosome appears as two Identical sister chromatids joined together at their centromeres and all along their arms by cohesion. The mitotic spindle begins to form. It is composed of the centrosome and micro tubules that extend from them. The radial arrays of shorter microtubules that extend from the centrosome are called asters (stars). The centrosome move away from each other<apparently propelled by d leveling microtubules between them. The microtubules extending from each chromosome can now invade the nuclear eave chromosome. The chromosome have become even more condensed, each of the two chromatids of each chromosome now has a kinetochore,a special protein structure located at the centromere. Some of the microtubule attached to the kinetochore becoming kinetochore microtubules. This jack the chromosome back and front. Non kinetochore microtubule interacts with those from the opposite pole of the spindle. Early Prophase Late Prophase 2 Metaphase METAPHASE: This is the longest stage of mitosis< is the centromeres are now at the opposite pole. The chromosome convenes on the metaphase plate and an imaginary plane that is equidistance between the spindles two poles. The chromosome centromere lies on the metaphase plate for each chromosome, the kinetochore of the sister chromatids are attached to kinetochore microtubule coming from opposite pole. 3 Anaphase It is the shortest stage of mitosis. it begins when the cohesion protein are leaved, these allow the two sister chromatids of each pair to part suddenly. Each chromatids therefore becomes a full fledged chromosome. The two liberated chromosome begins moving two opposite ends of the cell as their kinetochore microtubule shortens. Because this microtubules are attached at the centromere region, the chromosome makes centromere first. The cell elongate as the non kinetochore microtubule lengthen. By the end of anaphase two ends of cell have equivalent and complete collection of chromosome Early Anaphase Late Anaphase 4 Telophase The two daughter nuclei formed in the cell nucleus envelops arrived from the fragment of the parent cell. Sex nuclei envelop another portion of endo - membrane system. The chromosome becomes less condensed. Mitosis, the division of one nucleus into two genetically identical nuclei is now complete. 0 CYTOKINESIS The division of the cytoplasm is usually well underway by late telophase so the two daughter cell appear shortly after the end of mitosis. In animals cytokinesis involved the formation of cleavage furrow which pitches the cell into two. Two new "daughter cells" - the cycle is about to repeat itself. 1. 2. 3. 4. 5. 6. 7. THE SIGNIFICANCE OF MITOSIS It helps the cell to maintain proper size It helps in maintaining an equilibrium in the amount of DNA and RNA in the cell It provides the opportunity for the growth and development to organ and the body of the organism The old decaying and dead cell of the body are replaced In certain organism, the mitosis is involved in asexual reproduction The gonad and the sex cell depend on the mitosis for the increase in their number. The cleavage of egg during embryogenesis involved mitosis. 2. 1 MEIOSIS It can be defined as a process by which the chromosome in an organism is reduced into half of its complement in the process of gamete formation. There are distinct phases namely: reductional and equational division or meiosis1 and meiosis2 respectively. Meiosis1 can be divided into stages with their first five i.e. (leptotene, zygotene, pachytene, diplotene, diakinesis) Stages been referred to as prophase1. The other three stages are metaphase1, anaphase1 and telophase1. Prophase1 is the longest stage of meiotic division. LEPTOTENE (LEPTONEMA): The pro leptotene stage closely resembles with the early mitotic prophase.in this stage the chromosome are extremely thin, long, uncoiled, longitudinally single and slender threadlike structures. In the leptotene stage the chromosomes at this stage becomes uncoiled and assumes a threadlike shape. The chromosomes at this stage take out a` specific orientation inside the nucleus the end of the chromosomes converge towards one side of the nucleus that side where the centromeres lies. The centrioles duplicate each daughter centrioles migrate towards the opposite pole of the cell. The centrioles duplicate and therefore each pole of the cell possess two centrioles of a single diplosome. ZYGOTENE(ZYGONEMA): the pairing of homologous chromosomes takes place. The homologous chromosomes which come from the mother (by ova) and father(by sperm) are attracted towards each other and there pairing takes place known as synapses which are exact and specific. The paired homologous chromosomes are formed by synaptonema complex (sc). This complex extends along the whole length of the paired chromosome and is usually anchored at either end of the nuclei envelope. S.c helps to stabilize the pairing of homologous chromosomes and to facilitate cytogenetical activity called bi combination or crossing over (occurring during pachytene) PACHYTENE: the pair of chromosomes becomes crested spirally around each other and can not be distinguished separately. Pairing of homologous chromosome is completed and they now form bivalent or petards. The number of bivalent is equal to the haploid number of chromosomes. A change of parts between homologous chromosome also takes place during pachytene(crossing over). The chromosomes nucleoli and nuclei organizers are very distinct and the forces of paring which appears during zygotene start disappearing. DIPLOTENE: in diplotene, unpairing or desynapses of homologous chromosomes is started and chiasmata are first seen. The chromatids of each tetrad are usually clearly visible but the synaptonema complex appeared to be dissolved, living participating chromatids of they paired homologous chromosomes physically joined at one or more discrete point called chiasmata. This point are here crossing over take place. Often there is some unfolding of the chromatids at this stage, allowing for RNA synthesis and cellular growth. DIAKINESIS: in diakinesis, the bivalent chromosomes become more condensed and evenly distributed in the nucleus. The nucleus detaches from the organizer and ultimately disappears. The nuclear envelop breaks down. the chiasma move from the centromere towards the end of the chromosome to the intermediate chiasmata diminish. This type of movement of chiasmata is known as Terminalization. The chromatids remain connected by the terminal chiasmata and this exist up to the metaphase. PROMETAPHASE: in the prometaphase, the nuclear envelope disintegrates to the microtubules get arranged in the form of spindle in the two centrioles which occupy the position of two opposite poles of the cells. The chromosome become greatly coiled in the spiral manner and get arranged on the equator of the spindle. METAPHASE I: It consists of spindle fibre attachment to chromosomes chromosomal alignment of the equator. The microtubules are attached with the centromeres of homologous chromosome of each tetrad. The centromere of each chromosome is directed towards the opposite poles. The repulsive forces between the homologous chromosome increasingly greatly and the chromosome become ready to separate. ANAPHASE I The homologous separate and move apart with the centromere leading the way to the poles. This process completes the halving of the chromosome number since it’s the whole chromosome(and not chromatids) each containing sister chromatids. TELOPHASE I The chromosome movement has stopped as they are now separated in different cells. As only one partners of homologous pair goes to one pole, only half of the somatic number of chromosome reaches one pole. EQUATIONAL PHASE (MEIOSIS II): This phase is essentially similar to mitosis in which the sister chromatids now separate and enter into different cells. PROPHASE II: The chromosome becomes visible as tiny thread like structures in the cells. They continue to condense and thickened. The phase is short lived. METAPHASE II: Each chromosome now appear doubled and is joined together only at the centromeres. The spindle are organized on each side of the region as the chromosome align the muscles. ANAPHASE II: Each chromosome divides equationally producing 2 daughter chromosome each of which now moves in opposite direction. TELOPHASE II: The separation of the chromatids occurred. Four groups of chromosome are organized. 3. MENDELIAN LAW - Principles of segregation: states that the two alleles of a character in the first filia generation (F1) do not fuse together but exist independently of each other and pass on to the next generation without been influenced by each other. - Principle of independent assortment states that separation of one gene pair occurs independent of any other pair. 4. GENE INTERACTION Gene interaction is a condition where a single character is governed by 2 or more genes and every gene affects the expression of other genes involved. Gene Interaction Supplementary gene interaction Epistasis Duplicate Factor Inhibitory Factor Polymerism or Addictive Factor F2 Ratio 9:3:4 12:3:1 15:1 13:1 9:6:1 Test Crossed Ratio 1:1:2 2:1:1 3:1 1:3 1:2:1 Intra-allelic: This is when one allele affects the expression of another allele in the same gene locus. It’s a measure of how common an allele is in the proportion of all allele at one gene locus. Complete Dominance: is when one allele is completely dominant over the other allele, and there are no intermediate phenotypes e.g. eye color Co-Dominance: is a form of inheritance in which both alleles are equally shown e.g. A, B blood is the co-dominant relationship between A protein & B protein both expressing themselves completely AO ( type O allele means there is no protein), A is dominant and O is recessive. B.O is also the same. Co-dominance Working Example A B O Blood group Human blood is classified into four groups based on the antigen on the surface of the blood cell. An antigen is a protein that acts as the signal, enabling the body to recognize foreign substances that enters the protein. When foreign substances enter the body, the antigen responds by producing antibody i.e. antigen means antibody producing substance. Human blood types are controlled by 3 allele ‘IA ,IB and I’ the allele IA and IB are co-dominant (both are expressed together) and both are dominant to ‘I’ allele. BLOOD TYPE ANTIGEN GENOTYPE A A Ia ia or IAi B B Ib iB or Ibi Ab A &b IA ib O None Ii 1. A woman with type O blood and a man who is type AB are expecting a child. What are the possible blood types of the kid. 2. What are the possible blood types of a child whose parent are both heterozygous for B blood type. 3. What are the chances of a woman with blood type AB & a man with type A having a child type O. 4. Determine the possible genotype and phenotype with respect to blood group for a couple whose blood group are homozygous A and heterozygous B. 5. Ajibise is blood type O, she has two elder brother with blood type A & B, what are the genotype of her parents with respect to this traits. 6. A test was done to determine the biological father of a child. The child blood type is A and the mother is B. Ridwan has a blood type O and alfa have a blood type AB. Who is the biological father. Note A donate to A only, A accept from A & O B donate to B and B accept from B & O AB donate to AB, AB accepts from A,B,AB,O O donate to A,B,AB,O, o accepts from O only. Solution 1. Woman (O) - i i Man (AB) - IAIB 2 IA i : 2IBi 1 : 50% i i 1 50% IA i IB i IA IB IA i IB i Incomplete Dominance: is a form of inheritance in which the heterozygous alleles are both expressed, resulting in a combine phenotype e.g. ‘A’ red and a white allele gives pink. Incomplete dominance is most commonly found in plants. Factors Affecting Gene Interaction i. Penetrance: is how often a gene is expressed i.e. percentage of people who have the gene and who develop the corresponding phenotype. A gene with incomplete (no penetrance) may not be expressed even when the trait is dominant or when it is recessive and the gene responsible for that trait is present on both chromosome. Penetrance of the same gene may vary from person’s age even when the abnormal allele is not expressed (non penetrance) The unaffected carrier of the abnormal allele can pass it to children who may have clinical abnormalities. ii. Expressivity: is the extent to which a gene is expressed in one person. It can be graded at a percentage e.g. when a gene have 50% expressivity, only half of the features are present or the severity is only half of what can occur with full expression. Expressivity may be influenced by the environment and by other genes so, people with the same gene may vary in phenotype, expressivity can vary among the member of the same family. iii. Sex Limited Inheritance: A trait that appear in only one sex. It also refers to special cases in which sex hormone and other physiological differences between male and female alters the expressivity and penetrance of a gene e.g. premature baldness is an autosomal dominant trait but such baldness is rarely expressed in female and then usually only after menopause. iv. Genomic Imprinting: is the differential expression of genetic material depending on whether it has been inherited from the father or mother. However, in less than 1% of allele, expression is possible only from the paternal or maternal allele e.g. expression of gene for insulin-like growth factor. It is normally expressed only from paternal allele. v. vi. Co-dominance Chromosomal inactivation: In females who have more than one X chromosome (except in all but one of the X chromosome is inactivated; i.e. most of the allele on that chromosome are not expressed. Inactivation occurs individually in each cell early in foetal life. Sometime it is the X from the other that is inactivated or from the father. However, some of the allele from inactive ‘X’ chromosome do express. Many of these alleles are on chromosomal region corresponding to regions of the Y chromosome. Multiple Factor or Multiple Gene Multiple factor or multiple genes is two or more pair of allelic gene that acts as unit and affect a part of a person’s characteristics. A gene that individually exacts a slight effect and phenotype but along with few or many other gene that control quantitative trait is called polygene or multiple factor. a. b. c. d. e. f. Characteristics of Multiple Genes Each contributing allele in series of multiple genes produce an equal effect. Effect of each contributing allele are cumulative/additive There is no dominant, rather there exist pairs of contributing alleles. There are no epitasis (masking of the phenotype) of different loci. The environmental condition have a considerable effect on the phenotypic expression of polygene of the quantitative traits. There is no linkage. g. The genotype determines the range at which an individual will occupy with regards to a given quantitative character. 5. MULTIPLE ALLELES Multiple alleles (Multiple factors) is a type of non-Mendelian inheritance pattern that involves more than just the typical two alleles that usually code for a certain characteristic in a species. With multiple alleles, that means there is more than two phenotypes available depending on the dominant or recessive alleles that are available in the trait and the dominance pattern the individual alleles follow when combined together. Most of the time, when multiple alleles come into play for a trait, there is a mix of types of dominance patterns that occur. Sometimes, one of the alleles is completely recessive to the others and will be masked by any of those that are dominant to it. Other alleles may be codominant together and show their traits equally in the phenotype of the individual. There are also some cases where some alleles exhibit incomplete dominance when put together in the genotype. An individual with this type of inheritance connected to its multiple alleles will show a blended phenotype that mixes both of the alleles' traits together. Characteristics of multiple alleles Multiple alleles are always at the same locus on the chromosome. ,,, They always affect the same characters. wild type allele is nearly always dominant to all others at the same locus. It is also possible that they may have intermediate phenotypic expressions when two different alleles are brought together in the same genotype. When any two multiple alleles are crossed, the phenotype is of a mutant character and not of the wild type. Multiple alleles control the same character. But each of them is characterized by different manifestations. Significance of multiple alleles: The knowledge of the existence of allelic genes which act together modifying the effects of dominant gene is of great value in artificial breeding for producing varied varieties. The knowledge of alleles throws some light on the nature of genes. Laws of segregation and recombination of characters are based upon different alleles. Multiple alleles suggest that a gene can mutate in different ways. 6. VARIATION IN GENE EXPRESSION GENE EXPRESSION This is the process by which the information contained in the gene is converted into molecules that determine the properties of cells and viruses. The transfer of genetic information from DNA into protein constitutes the gene expression. The information transfer is accomplished by a series of events in which the sequence of the bases in the DNA is first copied into an RNA molecule and then, the RNA is used either directly or after some chemical modification, to determine the amino acid sequence of a protein molecule. The main ingredients necessary for complete translation are as follows; 1. Messenger RNA (mRNA): mRNA is needed to bring the ribosomal subunits together and to provide the coding sequence of bases that the determines the amino acid sequence in the resulting polypeptide chain. 2. Ribosomes: These components are particles in which protein synthesis takes place. They move along an mRNA molecule and align successive transfer-DNA molecules. The amino acids are attached one by one to the growing polypeptide chain by means of peptide bond. Ribosome consist of two subunit particles- in E.coli, there sizes are 30S(the small subunit) and 50S (the large subunit), the counterparts in eukaryotes are 40S and 60S.(The ‘S’ stands for Svedberg unit which measures the rate of sedimentation of a particle in a centrifuge and so it is an indicator of size). Together, the small and large particle forms functional ribosome. 3. Transfer RNA(tRNA): The sequence of amino acid in polypeptide is determined by the sequence in the mRNA by means of a set of adaptor molecules, the tRNA molecules, each of which is attached to a particular amino acid. Each group of the three adjacent bases in the mRNA forms a codon that binds to a particular group of three adjacent bases in the tRNA(an anticodon), bringing the attached amino acid into lone for addition to the growing polypeptide chain. 4. Amino acyl tRNA synthesis: this set of enzymes catalyzes the attachment of each amino acid to its corresponding tRNA molecules or a changed tRNA. 5. Initiation, elongation and termination factors; polypeptides synthesis can be divided into three stages-(i) initiation (ii) elongation (iii) termination, each of which requires specialized proteins. FACTORS AFFECTING GENE EXPRESSION Over expression of genes involved in the control of rate of biosynthesis can increase oil content. In some cases, introduction of additional copies of endogenous gene may interfere with gene expression, thereby, rather than enhancing the gene product. This phenomenon is called co- suppression, lowering gene expression by the use of anti-sense RNA which has been successful in reduction of poly galactouronase levels in tomatoes. 7. LINKAGE CROSSOVER AND GENETIC MAPPING Gene in the same chromosome will not assort independently and so mendel second law is not universal but its limited to gene in different chromosome. Therefore, gene which reside in the same chromosome are said to be limited. Such linkage may occur on one of the chromosome or connected on the sex chromosome. For instance when two alleles AB come form the same parent (AA/BB x aa/bb), they tend to enter different gamete and remain apart. The first is known as repulsion. Genetic mapping WORKED EXAMPLE: In drosophila, round eye (ec+) bristle (sc+) and crossed veins(cv+) are dominant over their respective allele, rough eye(ec), scute (sc) and cross veinless (cv), the 3 characters are sex linked. A drosophila of genotype ec+/sc+/cv+ is matedto another type of genotype ec/sc/cv and the F1 female test crossed to a male recessive for the 3 character. The following result were obtained. Sc+/ec/cv+ = 810 Sc/ec+/cv+ =89 Sc/ec+/cv =828 Sc+/ec/cv =103 Sc/ec/cv+ =62 Sc+/ec+/cv+=0 Sc+/ec+/cv =88 Sc/ec/cv =0 . Total = 1980 In other to construct d genetic map for the 3 genes, we need 1. Determine the linear order of the gene chromosome 2. Determine both single crossover (SCO) and double crossover(DCO) recombinant 3. use the information so obtain to calculate the relative distance between each gene 4. use the result to construct the genetic map For this particular example, we need to note the most frequent are the parental. The least frequent are the DCO recombinant. The other are the SCO recombinant THE LINEAR ORDER OF THE GENE In other to determine the linear order of the genes, it is necessary to look for the arrangement of the genes in the parental (i.e. the 2 classes that are excess) that gives the DCO recombinant(i.e. the least frequent classes). The example above the parental are 810 and 828, sc+/ec/cv+ and Sc/ec+/cv, while the DCO are Sc+/ec+/cu+ and Sc/ec/cv therefore we look for the parental that gives the 2 DCO recombinants. Since this arrangement give the 2 least frequent DCO, we therefore accept this arrangement as the correct order of the gene on the chromosome DETERMINATION OF SCO CLASSES In other to determine the SCO between each gene, we determine the single crossover classes using the arrangement of the parental Single crossover Sc+ and ec+ Sc+ ec cv+ Sc+/ec+/cv =88 X = + Sc ec cv Sc/ec/cv+ = 62 150 + + Distance between ec and cv Sc+ ec cv+ Sc+/ec/cv =103 X = + Sc ec cv Sc/ec+/cv+ = 89 192 Calculating the distance between the gene The distance between two genes is calculated by using the formular [(SCO+DCO) Total] X 100 [(88+62+0+0) 1980] X 100=7.6 or 7.6map unit ec+ and cv+ [103+89+0+0) 1980] X 100 [192 1980] X 100= 9.7 oe 9.7 map unit Construction Of Genetic Map The map is then constructed by drawing straight line indicating the distance between each gene. However, the map should be drawn to scale. Example 2: in maize non color booster (b) legaless (lg) and viresent (v) are recessive to their respective wild type (dominant). The F1 (heterozygous for all 3 characters) was test crossed to the homozygous single parent. The resultant progeny wave in the following proportions. What needs to be done is to move one of the outer gene into the middle INTERFERENCE If a cross over in one region of a chromosome does interfere with the crossover in the second region, the expected frequencies of the crossover is equal to the product the single crossover. Coefficient of coincidence measures the degree to which observe crossovers falls short od the expected. In this maize example however, expected frequencies of DCO is equal to 0.18*0.28=0.0504=0.05. Observe frequency of DCO is equal 0.18*0.22=0.04. Coefficient of coincidence (CI) is calculated by the formula If the crossover in one region does not interfere with another region, C.I complete interference give C.I = 0, C.I =0.8= partial. , Therefore DEOXYRIBONUCLEIC ACID DNA is the genetic material of all cellular organism and most of viruses. DNA carries the info needed to direct protein synthesis and replication. Protein synthesis is the production of the proteins needed by the cell or virus for its activities and development. Replication is the process by which DNA copies itself for each descendant cell or viruses passing on the information needed for protein synthesis. In most cellular organism, DNA is organized on chromosome located in the nucleus of the cell. DNA Structure A molecule of DNA consist of two chain strands composed of a large number of chemical compounds called Nucleotide, Linked together to form a chain. These chains are arranged like ladder that has been twisted into the shape of a winding staircase called a double helix, each nucleotide consist of 3 unit; a sugar molecule called deoxyribose, a phosphate group and one of four different nitrogen contain compounds called bases. The bases are; Adenine (A), Guanine (G), Thymine (T), Cytosine (C). deoxyribose molecule occupy the centre position in the nucleotide flanked by a phosphate group on one side and a base on the other. The phosphate group of each nucleotide is also linked to the deoxyribose of the adjacent nucleotide in the chain. These linked deoxyribose PO4 subunit form the parallel side rail of the ladder, the bases face inward towards each other, forming the rungs of the ladder. The nucleotide in one DNA strand has a specific association with corresponding nucleotide in the other DNA strand because of the chemical affinity of the bases, nucleotide containing adenine are always paired with nucleotide containing thiamine and nucleotide containing ‘C’ are always pairing with nucleotide G. the complementary bases are joined to each other by weak chemical bond called Hydrogen bond. PROTEIN SYNTHESIS DNA carries the instruction for the production of protein. A protein is composed of smaller compound called Ammo acid and the structure and function of protein is determined by the sequence of its aa. The sequence of Aa is determined by the sequence of nucleotide bases in the DNA. A sequence of 3 nucleotide bases called triplet, is a genetic code word or cordon that specify a particular aa. For instance, the triplet G.A.C is the cordon for aa leucine and triplet C.A.G is the codon for aa valine. A protein consisting of 100 aa is therefore encoded by DNA segment consisting of 300 nucleotide. Of the two polynucleotide chains that form a DNA molecule, only one strand contain the information needed for the production of a given aa sequence. The other strands aids in replication. Protein synthesis begins with the separation of DNA molecule into two strands in a process called transcription, a session of one strand act as a template or pattern to produce a new strand called messenger RNA (mRNA). The mRNA leaves the cell nucleus and attaches to the ribosome, specialize cellular structures that are the sight of protein synthesis. Aa are carried to the ribosome by another type of RNA called transfer RNA linked together in a particular sequence dictated by the mRNA to form a protein. A gene is equence of DNA nucleotides that occupy the order of aas in a protein viia an intermediary mRNA molecule. REPLICATION In most cellular organism, replication of a DNA molecule takes place in the cell nucleus and occurs just before the cell divide. Replication begins with the separation of the two polynucleotide chains each of which then act as a template for the assembly of a new complementary chain. As the old chain separate, each nucleotide in the two chain attract a complimentary nucleotide that has been formed earlier by the cell. The nucleotides are formed together by hydrogen bond to form the rings of a new DNA molecule. As the complimentary nucleotide are filled into place, an enzyme called DNA molecule. This process continues until a new poly nucleotide chain have been formed alongside the old one forming a double helix sugar molecule. Tools and Procedure Specialize enzymes called restriction enzyme found in bacteria act like molecular scissors to cut the PO4 backbone of DNA molecules at specific base sequences strand of DNA that have been cut with restriction enzyme are left with single stranded tail that are called sticky- ends, because they can easily realign with tails from advantage of restriction enzyme and the sticky-end generated by this enzyme to carryout recombinant DNA technology or genetic engineering. This technology involves removing a gene from one organism and inserting the gene into another organism. Application of DNA Research into DNA has had a significant impact on medicine. Through recombinant DNA technology, scientist can modify microorganism so that they become so called factories that produce large quantities of medically useful drugs. This technology is used to produce insulin which is used by some cancer patient study of human DNA are revealing gene that are associated with specific diseases such as cystic fibroses. This information is helping physician in diagnosing various diseases and it may lead to new treatment e.g. physician are using a technology called thimeraplasty which involves a synthetic molecule containing both DNA and RNA strand in an effort to develop a treatment for a form of hemophilia (inability of the blood to clot) Forensic science using techniques developed in DNA research to identify individuals who have committed crime. DNA from semen, skin or blood taking from the crime scene can be compared with the DNA of a suspect and the result can be used in count as evidence. DNA has helped taxonomy to determine the evolutionary relationship among plant, animal and other life forms. Closely related species have a similar DNA than those with distant relationship. One surprising finding that emerge is that vultures of Americans are more closely related to the clorks than to those of Europe, Asian, Agric. Techniques of DNA manipulation in form of genetic engineering and biotechnologist strains of crop plant to which gene have been transferred may produce higher yield and may be more resistant to pest and diseases, cattle have been similarly treated to increase milk and beef production as halves hogs to yield more milk with less fat. 9.0 NUCLEIC ACID AND CODING A gene is a molecular unit of heredity of a living organism. It is widely accepted by the scientific community as a name given to some stretches of deoxyribonucleic acids (DNA) and ribonucleic acids (RNA) that code for a or for a polypeptide RNA chain that has a function in the organism. A modern working definition of a gene is "a locatable region of genomic sequence, corresponding to a unit of inheritance, which is associated with regulatory regions, transcribed regions, and or other functional sequence regions” The Functional structures of gene. The vast majority of living organisms encode their genes in long strands of DNA (deoxyribonucleic acid). DNA consists of a chain made from four types of nucleotide subunits, each composed of: a five-carbon sugar (2'-deoxyribose), a phosphate group, and one of the four bases adenine, cytosine, guanine, and thymine. The most common form of DNA in a cell is in a double helix structure, in which two individual DNA strands twist around each other in a right-handed spiral. In this structure, the base pairing rules specify that guanine pairs with cytosine and adenine pairs with thymine. The base pairing between guanine and cytosine forms three hydrogen bonds, whereas the base pairing between adenine and thymine forms two hydrogen bonds. The two strands in a double helix must therefore be complementary, that is, their bases must align such that the adenines of one strand are paired with the thymine of the other strand, and so on. Chromosomes The total complement of genes in an organism or cell is known as its genome, which may be stored on one or more chromosomes; the region of the chromosome at which a particular gene is located is called its locus. A chromosome consists of a single, very long DNA helix on which thousands of genes are encoded. Prokaryotes—bacteria and archaea—typically store their genomes on a single large, circular chromosome, sometimes supplemented by additional small circles of DNA called plasmids, which usually encode only a few genes and are easily transferable between individuals. For example, the genes for antibiotic resistance are usually encoded on bacterial plasmids and can be passed between individual cells, even those of different species, via horizontal gene transfer. h Transcription The process of genetic transcription produces a single-stranded RNA molecule known as messenger RNA, whose nucleotide sequence is complementary to the DNA from which it was transcribed. The DNA strand whose sequence matches that of the RNA is known as the coding strand and the strand from which the RNA was synthesized is the template strand. Transcription is performed by an enzyme called an RNA polymerase, which reads the template strand in the 3' to5' direction and synthesizes the RNA from 5' to 3'. To initiate transcription, the polymerase first recognizes and binds a promoter region of the gene. Thus a major mechanism of gene regulation is the blocking or sequestering of the promoter region, either by tight binding by repressor molecules that physically block the polymerase, or by organizing the DNA so that the promoter region is not accessible. Translation Translation is the process by which a mature mRNA molecule is used as a template for synthesizing a new protein. Translation is carried out by ribosome, large complexes of RNA and protein responsible for carrying out the chemical reactions to add new amino acids to a growing polypeptide chain by the formation of peptide bonds. The genetic code is read three nucleotides at a time, in units called codons, via interactions with specialized RNA molecules called transfer RNA (tRNA). Each tRNA has three unpaired bases known as the anticodon that are complementary to the codon it reads; the tRNA is also covalently attached to the amino acid specified by the complementary codon. When the tRNA binds to its complementary codon in an mRNA strand, the ribosome ligates its amino acid cargo to the new polypeptide chain, which is synthesized from amino terminus to carboxyl terminus. During and after its synthesis, the new protein must fold to its active three-dimensional structure before it can carry out its cellular function. Nucleic acid A comparison of the two principal nucleic acids: RNA (left) and DNA (right), showing the helices and nucleobases each employs. Nucleic acids are polymeric macromolecules, or large biological molecules, essential for all known forms of life. Nucleic acids, which include DNA (deoxyribonucleic acid) and RNA (ribonucleic acid), are made from monomers known as nucleotides. Each nucleotide has three components: a 5-carbon sugar, a phosphate group, and a nitrogenous base. If the sugar is deoxyribose, the polymer is DNA. If the sugar is ribose, the polymer is RNA. Together with proteins, nucleic acids are the most important biological macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information—in other words, information is conveyed through the nucleic acid sequence, or the order of nucleotides within a DNA or RNA molecule. Strings of nucleotides strung together in a specific sequence are the mechanism for storing and transmitting hereditary or genetic, information via protein synthesis. TYPES OF NUCLEIC ACIDS Deoxyribonucleic acid Deoxyribonucleic acid (DNA) is a nucleic acid containing the genetic instructions used in the development and functioning of all known living organisms (with the exception of RNA viruses). The DNA segments carrying this genetic information are called genes. Likewise, other DNA sequences have structural purposes, or are involved in regulating the use of this genetic information. Along with RNA and proteins, DNA is one of the three major macromolecules that are essential for all known forms of life. DNA consists of two long polymers of simple units called nucleotides, with backbones made of sugars and phosphate groups joined by ester bonds. These two strands run in opposite directions to each other and are, therefore, anti-parallel. Attached to each sugar is one of four types of molecules called nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes information. This information is read using the genetic code, which specifies the sequence of the amino acids within proteins. The code is read by copying stretches of DNA into the related nucleic acid RNA in a process called transcription. Ribonucleic acid Ribonucleic acid (RNA) functions in converting genetic information from genes into the amino acid sequences of proteins. The three universal types of RNA include transfer RNA (tRNA), messenger RNA (mRNA), and ribosomal RNA (rRNA). Messenger RNA acts to carry genetic sequence information between DNA and ribosome, directing protein synthesis. Ribosomal RNA is a major component of the ribosome, and catalyzes peptide bond formation. Transfer RNA serves as the carrier molecule for amino acids to be used in protein synthesis, and is responsible for decoding the mRNA. In addition, many other classes of RNA are now known. Genetic coding. A Schematic diagram of a single-stranded RNA molecule illustrating the position of threebase codons. 10. MUTATION It is a sudden genetic change which is heritable. It involves alteration in the coding sequence of the gene. The change is usually in the sequence of the organic basis in the DNA constituting the particular gene. The original gene ‘A’ is dominant while the mutant gene ‘a’ is recessive. The mutation is a reversible process and the recessive allele ‘a’ will mutate back to its former form ‘A’ although not necessarily at the same rate that ‘A’ mutate to ‘a Effect of mutation on gene activity. Normally, the activity of a gene is lost due to mutation. This is the reason while the original or wild type genes are dominant and the mutant genes are recessive. In a diploid (2n) organism, if a mutation occurs in one of the genes, it leads to heterozygosis since other alleles remain unaffected and because of the presence of the wild type, a recessive mutation is not expressed. In a haploid (n) organism which have only one copy of each gene, each and every mutation is expressed. Fate of undesirable mutation Undesirable mutation are selected against by the environment therefore, the probability of such mutant are lost forever or eliminated from a population are greater in haploid than in diploid. Mutation in Somatic cells To get transmitted to the progeny through the gamete use the result that they are lost with the death of the organism. In vegetatively propagated or asexually reproducing organism. Somatic mutation are transferred to the progeny and therefore perpetuated. Detection of Mutation Mutation are usually detected since they bring about phenopitic change in the organism. TYPES OF MUTATION a. Dominant Vs Recessive Mutation: Mutation which is expressed in the first filial generation (f1) of all organism which arises from the mutant germplasm of a diploid organism is reffered to as dominant mutation. It is usually expressed in the heterozygous condition and is therefore easy to detect. On the other hand, mutation which is expressed in the second filial generation (F2) and in only small fraction of its progeny is known as recessive mutation. Recessive are not lethal mutation and the most difficult to detect and at the same time most frequent. However, recessive mutation are of great evolutionary significance because they can be perpetuated and maintain in heterozygous condition. b. Germinal Mutation: occurs in the germ plasm (germline) of an organism. It may be expressed in its lifecycle or expressed in the offspring. c. Recurrent Vs Non-recurrent mutation: In recurrent mutation, each mutational event occur regularly with characteristics frequency. It is an agent of change in the gene frequency in a PP. non-recurrent mutation on the other hand is a mutational event that give rise to first one representative of mutated gene or chromosome in the PP. it is a unique event and the product have very little chance of survival. It is therefore of little importance in changing the gene frequency in a PP. d. Neutral Mutation: is a unique mutation that is neutral with respect tofitness of the individual. e. Lethal Mutation: is a mutational event which leads to the death of the individual in which it occurs. As the case with the dominant mutation, lethal mutation is easy to detect since it leads to the death of the individual carrying it. f. Deleterious Mutation: is a mutational event which is detrimental to the gene of the individual. It may be lethal or decrease the physiological function of the individual concerned. g. Reverse Mutation: sometimes, Mutants reverse back to the wild type due to reverse mutation e.g. A forward mutation in a red flower plant may result in white flowered plant and a reverse mutation in the white flower plant may result in the red flower plant. Reverse mutation are very useful in genetic studies because they can be selected much more easily. h. Suppressor Mutation: Sometime, a forward mutation at one locus may hide the effect of another forward mutation and a combination of the two appears as if a reverse mutation has taken place. Such mutation which suppress the phenotype of other mutation are known as suppressor mutation. i. Mutable and Mutator gene: genes which are capable of undergoing mutation are known as mutable genes and the gene which control the mutation frequency of other gene are known as mutator gene . Sometimes, a single mutator gene affects mutator frequency of a number of loci. However, there are examples of mutator gene that affect only one mutable gene. In Males for example, the mutation frequency of the gene controlling Anthocyanide production is under the control of a single mutator locus. Induction of Mutation Apart from mutation that arises spontaneously, mutation can be induced. A detectable mutation occur if the change cordon stands for a different aas sequence of the protein, and therefore it is not expressed. a. Ionizing radiation :such as Xray causes breakage in the DNA synthesis result in mutation. b. Ultraviolent radiation: ultraviolent rays cause hydration and deammation which interferes with DNA synthesis, resulting in mis-replication and mutation c. Chemical mutagen: These include nitrous acid, carboxylic compound and nitrogen musterds. The overall effect is that they cause abnormal base, DNA, distortion of normal DNA double helix, addition or division of single base pairs. This result in different tyoe of architectural change such as transition, transaction and frame shift as well as nonsense mutation and mix sense mutation. Frame shift may occur due to division or addition of bases which causes gross change in the aa sequence of protein since it affect the reading frame of codon beginning from the site of . transistion and translation of the gene is therefore affected because this process start from a fixed point. Transition: Transition involves changes from one purine to another purine or pyrimidine to another pyrimidine. Transaction: This involve a change from purine to pyrimidine or vice versa A=T C=G A=T T=A Mix sense Vs Nonsense mutation: mix sense in mutation occur if the change codon stands for a different aa which grossly affects the catalytic properties of the protein. Nonsense mutation occurs when a codon which stand for an aa is change to a chain-terminating one 11. POPULATION GENETICS It is the study of genetic variation in a population for many years. Factors that Affect Influence Genetic Change In a Population a. Mutation: They are the change that occur to the gene of an individual during a lifetime and are transmitted directly to the offspring. It occurs at the level of molecular genetic material, DNA. Mutation are replacement of one nucleotides base by another and may allow an individual to adapt to the changing environmental occurrences e.g. Climate b. Natural Selection: is the principal way that organism adapt to their environment. It is very basis of evolution of all living organism. In natural selection, a trait that provides individual with greater evolutionary fitness( reproductive success) will increase in frequency over generations among that make individual less fit may decrease and initially rear gene result from a single mutation will become common in a PP for it to provide an effect that enable individuals to adapt to their environment. Those with the beneficial gene will survive longer and produce more offspring than those without such gene. Offspring who inherited such favorable gene will also have more offspring and individual with genes will soon outnumber those without the gene. c. Random genetic drift: beside mutation and genetic gene, pure chance factor may choose the frequencies of the genes present in a PP. most gene occurs in two or more forms of alleles. For each gene an individual inherit one allele from the mother and from the father even though a parent may have two different allele of the gene, only one will pass down to a child. The allele to the passed down is determined entirely by chance at the time of conception. Random genetic drift therefore refers to the change in a pp, gene frequency resulting from the change factor due to genetic drift certain allele will therefore appear from a pp even if they confer evolutionary fitness simply because they occur in a very low frequencies at the same time. Other alleles will become wide spread because they occur in higher frequency. Random genetic drift does not usually have a major effect on a pp gene pool if the size of the pp is larger. If the pp is small, it can dramatically influence gene frequency. Epidemic, disease, wars and destructive natural events such as volcanic eruption, earthquake and flood can create situation known as bottle neck. The calamity leads a reduce a pp in which the genes of only a few survivors remain. Gene Flow and Migration Gene flow occurs directly, when individual from one pp meet with others from another thereby introducing their genes into the pp. increase gene flows between pp generally make them more alive than they have been previously. Gene flow also occur indirectly for example if a pp A interbreed with pp B and B interbreed with C, some gene from pp A will pass to pp C in this ways flow occurs across vast geographic regions and connect distant pp. 11.0 HARDY-WEINBERG A set of algebraic formulae that describe how the proportion of different genes. The hereditary unit that determine a particular allele should occur in pp. the rule also reveals how often particular genotype, the actual combination of gene and individual carries and may pass on to the offspring should appear in the same proportion by studying this alleles and genetic frequency, scientist can identify pp that are changing genetically oe evolving. They can also predict the occurrence of genetic effect in a pp. Each individual in a pp has two allele of every gene. This allele may be the same and one allele maybe dominant over the other for example: in a sample group of 100 individual from a particular pp, the gene from a certain individual have allele Aa in which A is dominant over a, each individual of the group carries each of this allele in one of the pp or genotype AA or Aa. In a sample of group of 100 people, 33 people has AA genotype 54 has Aa genotype and 13 have aa genotype. The actual frequency of the two alleles in the group i.e. the number of each allele type by the total number of all alleles (2 each from the 33 individual with the AA genotype and one each from the 54 individual with the Aa genotype) by 200, the total number of all allele, 2 each from 100 individuals. The hardy-weinberg rule uses the actual allele frequency of a pp to predict the pp expected genotypic frequency. i.e. the number of genotype that should be in a pp. Assuming that a gene pp has 2 pp Aa whose frequencies are represented mathematically as ‘p & q’ that can form the 3 type AA, Aa, aa. The following formular can be used to predict genotypic frequency Frequency AA: p x p= p2 Aa: p x q= 2pq aa : q x q= q2 p2+2pq+q2 is used to find genotypic frequency i. For example: If the frequency of the A allele in a pp is =0.60 then the expected genotypic frequency with Aa genotype is 0.36 i.e. (0.60 x 0.60 which is 0.36) expected genotype frequency. Scientist compare a pp expected genotypic frequency to its actual genotypic frequency (determined by dividing the total no of each genotype in the group by the total number individual number in the group). To determine whether the pp is maintaining the same ratio or equilibrium of the genotype over time according to the rule each equilibrium remain the same in as long as 4 conditions are meant; i. Individual must select or mate randomly without regards or phenotypic trait ii. No genotype can be favoured in such a way that it will increase the frequency in pp ovetime. iii. No new allele can be deduced to the pp or by alleles that have changed or mutated from one form to another. The number of individual and genotype in pp remain high. The pp that meet this condition maintain the same proportions of different genes overtime i.e. genetic make of pp never changes. 33 have AA -> 33+33=66 54 have Aa 13 have aa A= 33+ 33+54=120 a= 54+ 13 + 13=80 A+a=200(120+80) Actual allele frequency A= = 0.6 Expected genotypic frequency of AA= 0.6 x0.6 = 0.36 Actual genotypic frequency = = 0.33