Cell & Molecular Biology PDF - BWJ21203

BWJ21203 CELL & MOLECULAR BIOLOGY Mendel, genes and chromosomal inheritance 8 Mendel and the Gene Idea ◦ Eye colour (blue, green or grey), hair colour (black, brown, blond or red) are examples of heritable traits observed in a population ◦ One possible explanation of heredity is the “ble...

BWJ21203 CELL & MOLECULAR BIOLOGY Mendel, genes and chromosomal inheritance 8 Mendel and the Gene Idea ◦ Eye colour (blue, green or grey), hair colour (black, brown, blond or red) are examples of heritable traits observed in a population ◦ One possible explanation of heredity is the “blending” hypothesis, the idea that genetic material mixes in the same manner as paint ◦ In this hypothesis, over many generations, a freely mating population will give rise to a uniform population ◦ However, our everyday observation contradicts this hypothesis ◦ Also, the blending hypothesis fails to explain other phenomenon as traits skipping a generation Mendel and the Gene Idea ◦ An alternative to the blending model is the “particulate” hypothesis or the gene idea ◦ According to this model, parents pass on discrete heritable traits that retain their separate identities in offspring, more like a bucket of marbles than a pail of paint ◦ Like marbles, genes can be passed along generation after generation in undiluted form Mendel and the Gene Idea ◦ Gregor Mendel began breeding garden peas in the abbey garden in order to study inheritance ◦ Mendel probably chose to work with peas because they came in many varieties e.g. purple flowers, white flowers ◦ Geneticists use the term character for heritable features, such as flower colour ◦ Each variant for a character, such as purple or white, is called a trait Mendel and the Gene Idea ◦ The use of peas gave Mendel strict control over which plants mated with which ◦ Each pea has both male and female organs and are capable of self fertilization ◦ Mendel chose to track discrete characters that were “either-or” e.g. purple or white flowers ◦ Mendel also started his experiments with varieties that were true-breeding, which means that when the plants self-pollinate, all their offspring are of the same variety Mendel and the Gene Idea ◦ In a typical breeding experiment, Mendel would cross pollinate two contrasting, true-breeding pea varieties, P generation ◦ This mating or crossing of two varieties is called hybridization ◦ The hybrid offspring are called F1 generation ◦ Allowing these F1 generation to pollinate produces the F2 generation ◦ It was mainly quantitative analysis of the F2 generation that revealed the fundamental principles of heredity that are known as the law of segregation and the law of independent assortment Mendel and the Gene Idea ◦ Watch this video for another example of Mendel’s pea experiments looking at pea colour ◦ https://www.youtube.com/watch?v=cWt1RFnWNzk Mendel and the Gene Idea ◦ Mendel’s Law of Segregation By law of segregation, the two alleles for a character are packaged into separate gametes ◦ Alternative versions of genes (different alleles) account for variations in inherited characters ◦ For each character, an organism inherits two alleles, one from each parent ◦ If the two alleles differ, then one, the dominant allele, is fully expressed in the organism’s appearance; the other the recessive allele, has no noticeable effect on the organism’s appearance ◦ The two alleles for each character segregate during gamete production Mendel and the Gene Idea ◦ Some Useful Genetic Vocabulary An organism having a pair of identical alleles is said to be homozygous e.g. a true breeding purple flowered pea (PP) or a white flowered pea (pp) ◦ An organism having two different alleles for a gene are said to be heterozygous (Pp) ◦ Because of dominance and recessiveness, an organism’s appearance does not always reveal it’s genetic composition ◦ An organism’s appearance is called its phenotype and it’s genetic makeup is called its genotype ◦ PP and Pp have the same phenotype (purple) but different genotypes Mendel and the Gene Idea ◦ The Testcross Consider a purple pea flower ◦ We cannot tell from the flower’s genotype (whether it is homozygous or heterozygous) from the phenotype (purple) ◦ However, if we cross this pea plant with one having white flowers (pp), the appearance of the offspring will reveal the genotype of the purple plant Mendel and the Gene Idea ◦ The Testcross What would happen in a mating of parental varieties differing in two characters – a dihybrid cross? E.g. seed colour (yellow/green) and seed shape (round/wrinkled) ◦ Mendel knew that the allele for yellow seeds is dominant (Y), green is recessive (y), round is dominant (R) and wrinkled is recessive (r) ◦ Are these two characters, seed colour and seed shape, transmitted as a package or are they independent? Mendel and the Gene Idea ◦ The Testcross If the two characters segregate dependently (together) the F1 hybrids can only produce the same two classes of gametes that they receive from the parents (yellow-round and green-wrinkled) ◦ If the two characters segregate independently, four classes of gametes will be produced by the F1 generation, and there will be a 9:3:3:1 phenotypic ratio ◦ Mendel’s results support this hypothesis, called independent assortment Extending Mendelian Genetics ◦ In the 20th century, geneticists have extended Mendelian genetics to diverse organisms and to patterns of inheritance more complex than what Mendel described ◦ It was brilliant (or lucky) that Mendel chose pea plant characters that turned out to have a simple genetic basis ◦ The relationship between genotype and phenotype are rarely that simple Extending Mendelian Genetics ◦ Dominance Dominance/recessiveness can range from complete dominance, various stages of incomplete dominance to codominance ◦ They reflect the mechanisms by which specific alleles are expressed in phenotype and do not involve the ability of one allele to subdue another at the level of DNA ◦ They do not determine the relative abundance of alleles in a population Extending Mendelian Genetics ◦ Incomplete Dominance Incomplete dominance is a form of inheritance where the F1 hybrids have an appearance between the phenotype of two parental varieties ◦ For instance, when red snapdragons are crossed with white snapdragons, all F1 hybrids have pink flowers ◦ This pink phenotype results from flowers of heterozygotes having less red pigment than the red homozygotes Extending Mendelian Genetics ◦ Incomplete Dominance However, incomplete dominance is not evidence for the “blending” hypothesis which predicts that red or white traits could never be retrieved from the pink hybrids ◦ In fact breeding the F1 hybrids produces F2 offspring with the ratio of 1 red to 2 pink to 1 white ◦ The segregation of the red and white alleles confirms that alleles for flower colour are heritable factors that maintain their identity in the hybrids Extending Mendelian Genetics ◦ Codominance Codominance is a phenomenon where both alleles separately manifest in the phenotype ◦ One example is the three different human blood groupings called the M, N and MN blood groups ◦ These groupings are based on two specific molecules located on the surfaces of red blood cells ◦ People with M have one type of molecule (M antigen), people with N have the other type (N antigen) and people with MN have both Extending ◦ Multiple Alleles Mendelian Genetics Most genes exist in more than two allelic forms ◦ The ABO blood groups are one example of multiple alleles of a single gene ◦ There are four different possible phenotypes for this character: A, B, AB or O ◦ These letters refer to two carbohydrates, the A substance and the B substance which may be found on the surface of red blood cells ◦ A person may have one substance or the other (type A or B), both (type AB) or neither (type O) Extending Mendelian Genetics ◦ Multiple Alleles Matching compatible blood groups is critical for blood transfusions ◦ If the donor’s blood is has a factor (A or B) that is foreign to the recipient, specific proteins called antibodies will cause the foreign molecules to agglutinate (clump together) and kill the recipient ◦ The four blood groups result from various combinations of three different alleles of one gene, IA (A carbohydrate) IB (B carbohydrate) and IO (neither A nor B) Extending Mendelian Genetics ◦ Multiple Alleles Both IA and IB are dominant to the IO allele ◦ Thus, IAIA and IAIO have the A blood type, IBIB and IBIO have the B blood type and IOIO have the O blood type ◦ IA and IB are codominant; both are expressed in the phenotype of the IAIB who has the AB blood type Extending Mendelian Genetics ◦ Pleiotropy So far we have treated one gene as though it affects one phenotypic character ◦ However, most genes have multiple phenotypic effects ◦ The ability for a gene to affect an organism in multiple ways is called pleiotropy (pleion, more) ◦ For example sickle-cell disease can cause multiple symptoms Extending Mendelian Genetics ◦ Epistasis In some cases, a gene at one locus alters the phenotypic expression of a gene at a second locus, a condition known as epistasis (standing upon) ◦ For example, in mice, B black coat is dominant to b brown coat ◦ A second dominant gene locus, C (colour) results in the deposition of pigment and allows for black or brown, depending on the genotype of the first locus ◦ However, if the mouse is homozygous cc then the coat colour will be white regardless of the genotype at the black/brown locus Extending Mendelian Genetics ◦ Epistasis What happens if we mate black mice that are heterozygous (BbCc)? ◦ Although the two genes affect the same phenotypic character (coat colour), they follow the law of independent assortment ◦ Thus the ratio of phenotypes among F2 offspring is 9 black to 3 brown to 4 white Extending Mendelian Genetics ◦ Polygenic Inheritance Mendel studied characters that could be classified by either-or basis, such as purple colour versus white flower colour ◦ For many characters, however, such as human skin colour and height, an either-or classification is impossible as these characters vary in a continuum (in gradations) ◦ These are called quantitative characters ◦ Quantitative variation usually indicates polygenic inheritance, an additive effect of two or more genes on a single phenotype Extending Mendelian Genetics ◦ Polygenic Inheritance There is evidence that skin pigmentation in humans is controlled by at least three separate genes (probably more but we simplify) ◦ Consider dark-skin alleles (A, B, C) contributing one “unit” of darkness to the phenotype ◦ These are incompletely dominant to other alleles (a, b, c) ◦ AABBCC person would be very dark, aabbcc would be very light and AaBbCc would have an intermediate shade ◦ AaBbCc and AABbcc would make the same genetic contribution ◦ This polygenic inheritance would result in a bell-shaped curve called a normal distribution ◦ Environmental factors such as exposure to the sun, also affect the skin-colour phenotype Extending Mendelian Genetics ◦ Nature Versus Nurture: The Environmental Impact on Phenotype Phenotype depends on environment as well as on genes ◦ A single tree, locked into its inherited genotype, has leaves that vary in size, shape and greenness depending on the exposure to wind and sun ◦ For humans, nutrition influences height, exercise alters build, sun-tanning darkens the skin and experience improves performance on intelligence tests ◦ Even identical twins accumulate phenotypic differences as a result of their unique experiences Extending Mendelian Genetics ◦ Nature Versus Nurture: The Environmental Impact on Phenotype Whether it is genes or the environment – nature or nurture – most influences human characteristics is a very old and hotly contested debate ◦ We can say that the product of a genotype is generally not a rigidly defined phenotype but a range of phenotypic possibilities over which there is variation due to environmental influence ◦ This phenotypic range is called the norm of reaction for the genotype ◦ There are also cases where a genotype mandates a very specific phenotype such as a person’s ABO blood group ◦ Generally norms of reaction are the broadest for polygenic characters ◦ Geneticists refer to such characters as multifactorial, meaning that many factors, both genetic and environment influence the phenotype