GENETICS THE SCIENTISTS

Transcription

1 GENETICS THE SCIENTISTS R E V I E W The Academic Support Daytona State College (Science 108, Page 1 of 31)

2 Harvey William Harvey ( ) wrote a treatise on reproduction and development patterned after Aristotle s work. He is credited with the earliest statement of the theory of epigenesis, which posits that an organism is derived from substances present in the egg that differentiate into adult structures during embryonic development. Epigenesis holds that structures such as body organs are not initially present in the early embryo but instead are formed de novo (anew). The Academic Support Daytona State College (Science 108, Page 2 of 31)

3 Schleiden and Schwann Around 1830, Matthias Schleiden, and Theodor Schwann proposed the cell theory, stating that all organisms are composed of basic units called cells, which are derived from similar preexisting structures. The idea of spontaneous generation, the creation of living organisms from nonliving components, was disproved by Louis Pasteur later in the century, and living organisms were considered to be derived from preexisting organisms and to consist of cells. The Academic Support Daytona State College (Science 108, Page 3 of 31)

4 Darwin The Academic Support Daytona State College (Science 108, Page 4 of 31)

5 Mendel Gregor Mendel Proposed the existence of particulate unit factors (genes) are passed from generation to generation Proposed four postulates of inheritance Unit factors (alleles of genes) exist in pairs (in diploid) If an organism has two different alleles (heterozygous) then one is dominant and the other is recessive. One expresses phenotype in heterozygote, and the other is hidden in heterozygote The paired unit factors segregate independently during gamete formation (meiosis). All possible combinations of gametes will form with equal frequency Proposed that traits assort independently during gamete formation. Used true breeding strains of peas with seven characteristics, each characteristic had two contrasting traits. The Academic Support Daytona State College (Science 108, Page 5 of 31)

6 Mendel The Academic Support Daytona State College (Science 108, Page 6 of 31)

7 Mendel The Academic Support Daytona State College (Science 108, Page 7 of 31)

8 Hardy and Weinburg The relationship between the relative proportions of alleles in the gene pool and the frequencies of different genotypes in a population was described in the early 1900s in a simple mathematical model developed independently by the British mathematician Godfrey H. Hardy and the German physician Wilhelm Weinberg. The Academic Support Daytona State College (Science 108, Page 8 of 31)

9 Hardy and Weinburg Given 36% of the population is blue eyed (recessive phenotype) what is p and q? p 2, 2pq: Given that 36% is recessive then q 2 =.36, therefore q =.6 p + q = 1, therefore p =.4 p 2 =.16 and 2pq =.48 To double check p 2 + 2pq + q 2 = = 1 Therefore dominant phenotype = 16% Heterozygotes = 48% The Academic Support Daytona State College (Science 108, Page 9 of 31)

10 Hardy and Weinburg The Academic Support Daytona State College (Science 108, Page 10 of 31)

11 Luria and Delbruck In 1943, Salvador Luria and Max Delbruck presented the first direct evidence that mutations do not occur as part of an adaptive mechanism, but instead take place spontaneously and randomly. The Academic Support Daytona State College (Science 108, Page 11 of 31)

12 Lederberg and Zinder In 1952, Norton Zinder and Joshua Lederberg were investigating possible recombination in the bacterium Salmonella typhimurium. What they discovered was a process of bacterial recombination mediated by bacteriophages and now called transduction. The Academic Support Daytona State College (Science 108, Page 12 of 31)

13 Griffith Frederick Griffith in 1927 showed that avirulent strains of Diplococcus pneumoniae could be transformed to virulence. He speculated that the transforming principle could be part of the polysaccharide capsule or some compound required for capsule synthesis. Proved there was a transforming principle. The Academic Support Daytona State College (Science 108, Page 13 of 31)

14 Avery, McLeod and McCarty The 1944 publication by Oswald Avery, Colin MacLeod, and Maclyn McCarty concerning the chemical nature of a transforming principle in bacteria was the initial event leading to the acceptance of DNA as the genetic material. The Academic Support Daytona State College (Science 108, Page 14 of 31)

15 Hershey and Chase In 1952, Alfred Hershey and Martha Chase using Escherichia coli and an infecting virus (bacteriophage T2), demonstrated DNA, and not protein, is the genetic material. The Academic Support Daytona State College (Science 108, Page 15 of 31)

16 Chargaff Between 1949 and 1953, Erwin Chargaff and his colleagues used chromatographic methods to separate the four bases in DNA samples from various organisms. Quantitative methods were then used to determine the amounts of the four bases from each source. The proportions change from species to species. The Academic Support Daytona State College (Science 108, Page 16 of 31)

17 Chargaff Between 1949 and 1953, Erwin Chargaff and his colleagues used chromatographic methods to separate the four bases in DNA samples from various organisms. Quantitative methods were then used to determine the amounts of the four bases from each source. The Academic Support Daytona State College (Science 108, Page 17 of 31)

18 Chargaff Examples If A = 23% what is T, G and C? A = T; therefore T = 23% A + T + G + C = 100%; therefore G + C = 100% G + C = 54% G = C; therefore C = 27% and G = 27% The Academic Support Daytona State College (Science 108, Page 18 of 31)

19 Watson and Crick In 1953, James Watson and Francis Crick proposed that the structure of DNA is in the form of a double helix. The data available to Watson and Crick, crucial to the development of their proposal, came primarily from two sources: (1) base composition analysis of hydrolyzed samples of DNA and (2) X-ray diffraction studies of DNA. Watson and Crick s analytical success can be attributed to their focus on building a model that conformed to the existing data. The Academic Support Daytona State College (Science 108, Page 19 of 31)

20 Meselson and Stahl Matthew Meselson and Franklin Stahl The Meselson-Stahl experiment demonstrated that: DNA replication is semiconservative Each new DNA molecule consists of one old strand and one newly synthesized strand. The Academic Support Daytona State College (Science 108, Page 20 of 31)

21 Meselson and Stahl The Academic Support Daytona State College (Science 108, Page 21 of 31)

22 Taylor, Woods, and Hughes The Academic Support Daytona State College (Science 108, Page 22 of 31)

23 Ames In 1974, Bruce Ames developed a simple test for evaluating the potential of chemicals to cause cancer. The Ames test is based on the principle that both cancer and mutations result from damage to DNA, and the results of experiments have demonstrated that 90% of known carcinogens are also mutagens. Ames proposed that mutagenesis in bacteria could serve as an indicator of carcinogenesis in humans. A bacterial assay developed by Bruce Ames to detect mutagenic compounds; it assesses reversion to histidine independence in the bacterium Salmonella typhimurium. The Academic Support Daytona State College (Science 108, Page 23 of 31)

24 Ames Ames test The Ames test uses a number of different strains of Salmonella typhimurium selected for their ability to reveal the presence of specific types of mutations The Ames test is used extensively during the development of industrial and pharmaceutical chemical compounds Many known carcinogens have been shown by the Ames test to be strong mutagens. More than 60 compounds found in cigarette smoke test positive in the Ames test and cause cancer in animals. Note this is a first step, not proof of carcinogen. The Academic Support Daytona State College (Science 108, Page 24 of 31)

25 Nirenberg and Matthaei Nirenberg and Matthaei Cracked the genetic code by using nucleic acid homopolymers to translate specific amino acids. Added RNA homopolymers to the in vitro translation system to decipher which amino acids were encoded by the first few codons based on which amino acids were incorporated into the polypeptide. In 1961, Marshall Nirenberg and J. Heinrich Matthaei became the first to characterize specific coding sequences, laying a cornerstone for the complete analysis of the genetic code. Their success, as well as that of others who made important contributions in deciphering the code, was dependent on the use of two experimental tools, an in vitro (cell-free in a test tube) protein-synthesizing system and the enzyme polynucleotide phosphorylase, which allowed the production of synthetic mrnas. These mrnas served as templates for polypeptide synthesis in the cellfree system. RNA homopolymers RNA nucleotides with only one type of ribonucleoside RNA heteropolymers RNA nucleotides with two or more different ribonucleosides The Academic Support Daytona State College (Science 108, Page 25 of 31)

26 Nirenberg and Leder Nirenberg and Leder Developed the triplet binding assay to determine other specific codon assignments. In 1964, Nirenberg and Philip Leder developed the triplet binding assay, leading to specific assignments of triplet codons. Triplet binding essay In this technique ribosomes bind to a single codon of three nucleotides and the complementary amino acid charged trna will be able to bind. This technique took advantage of the observation that ribosomes, when presented in vitro with an RNA sequence as short as three ribonucleotides, will bind to it and form a complex similar to what is found in vivo. The triplet RNA sequence acts like a codon in mrna, attracting a trna molecule containing a complementary sequence. Such a triplet sequence in trna, that is, complementary to a codon of mrna, is known as an anticodon. The Academic Support Daytona State College (Science 108, Page 26 of 31)

27 Crick Wobble hypothesis Predicts that the initial two ribonucleotides of triplet codes are often more critical than the third. The third position of the codon-anticodon interaction would be less spatially constrained and need not adhere as strictly to the established base-pairing rules at the third position of the codon. An idea proposed by Francis Crick, stating that the third base in an anticodon can align in several ways to allow it to recognize more than one base in the codons of mrna. The Academic Support Daytona State College (Science 108, Page 27 of 31)

28 Holley In 1965, Robert Holley and his colleagues reported the complete sequence of trna Ala isolated from yeast. Of great interest was their finding that a number of nucleotides are unique to trna, each containing a so-called modified base. These modified structures are created after transcription of trna, illustrating the more general concept of posttranscriptional modification. Holley s sequence analysis led him to propose the two-dimensional cloverleaf model of trna. It had been known that trna has a characteristic secondary structure created by base pairing. Holley discovered that he could arrange the linear sequence in such a way that several stretches of base pairing would result. His arrangement, with its series of paired stems and unpaired loops, resembled the shape of a cloverleaf. The Academic Support Daytona State College (Science 108, Page 28 of 31)

29 Beadle and Tatum Beadle and Tatum Beadle and Tatum (1940 s) showed that nutritional mutations in the bread mold Neurospora caused the loss of an enzymatic activity that catalyzes an essential reaction in wild-type organisms One gene one enzyme hypothesis. The Academic Support Daytona State College (Science 108, Page 29 of 31)

30 Jacob and Monod Jacob and Monod In 1961, François Jacob and Jacques Monod described the operon model for the genetic control of lactose metabolism in E. coli. This work and subsequent research on the genetics of lactose metabolism established the operon as the basic unit of transcriptional control in bacteria. Despite the fact that, at the time, no methods were available for determining nucleotide sequences, Jacob and Monod deduced the structure of the operon genetically by analyzing the interactions of mutations that interfered with the normal regulation of lactose metabolism. The Academic Support Daytona State College (Science 108, Page 30 of 31)

31 Questions Prepared and Compiled from various sources by D. Leonard (Learning Specialist) The Academic Support Daytona State College The Academic Support Daytona State College (Science 108, Page 31 of 31)