Nature and origin of Life lecture 6

1. Nature and origin of Lifelecture 6 History part 2

2. TOPICS • Mendel genetics (sweet peas) • Fruit flies. • The shift to phages • Discovery of roles of nucleic acids and proteins. • DNA and the genetic code • The proteins and nucleic acid chicken and egg problem. • Items of concern in the origin of life

3. Gregor Mendel • Monk who investigated sweet peas • Mendelian Inheritance: • How sexual organisms reproduce Causes Loss of ½ genetic material for an offspring. Dominant and recressive genes.

4. Ploidy • The ploidy number is the number of paired chromosomes in the cell. • Humans are diploid. • Plants , insects amphibians and reptiles are often tetraploid. • A single human may have cells of different ploidy, so egg and sperm cells are monoploid, most other cells are diploid, but e.g. some muscle cells are tetraploid!

5. Zygosity From Wikipedia, Zygosity is the degree of similarity of the alleles for a trait in an organism. If both alleles are the same, the organism is homozygous for the trait. If both alleles are different, the organism is heterozygous for that trait. If one allele is missing, it is hemizygous, and, if both alleles are missing, it is nullizygos. Most eukaryotes have two matching sets of chromosomes; that is, they are diploid. Diploid organisms have the same genes on each of their two sets of homologous chromosomes, except that the sequences of these genes may differ between the two chromosomes in a matching pair and that a few chromosomes may be mismatched as part of a sex-determination system.

6. In prokaryotes All prokaryote Cells are haploid. Genetic variation can only be produced by Mutation, or Lateral Gene Transport

7. Mendel interpretation • Mendel factors = genes. • Dominant (A) and Recessive (a) • Possible pairings are AA, Aa, aA, aa. So dominant features will statistically appear in ¾ of offspring. • Mendel stated that each individual has two factors for each trait, one from each parent. Homozygous vs heterozygous. • Egg and sperm each possess both genes from the “grandparents”, but in transition to the next generation individual ½ of the genes are lost.

8. Mendel First Law, Law of Segregation • The Law of Segregation states that every individual possesses a pair of alleles (assuming diploidy) for any particular trait and that each parent passes a randomly selected copy (allele) of only one of these to its offspring. The offspring then receives its own pair of alleles for that trait. Whichever of the two alleles in the offspring is dominant determines how the offspring expresses that trait (e.g. the color of a plant, the color of an animal's fur, the color of a person eyes).

9. Law of Independent Assortment (The "Second Law") • The Law of Independent Assortment, also known as "Inheritance Law", states that separate genes for separate traits are passed independently of one another from parents to offspring. That is, the biological selection of a particular gene in the gene pair for one trait to be passed to the offspring has nothing to do with the selection of the gene for any other trait.

10. Mendel 2 • Mendel's conclusions were largely ignored. Although they were not completely unknown to biologists of the time, they were not seen as generally applicable, even by Mendel himself, who thought they only applied to certain categories of species or traits. A major block to understanding their significance was the importance attached by 19th-century biologists to the apparent blending of inherited traits in the overall appearance of the progeny, now known to be due to multigene interactions, in contrast to the organ-specific binary characters studied by Mendel • later work by biologists and statisticians such as R.A, Fisher showed that if multiple Mendelian factors were involved in the expression of an individual trait, they could produce the diverse results observed

11. Fruit Flies TheD. melanogaster lifespan is about 30 days at 29 °C (84 °F). The developmental period for fruit flies varies with temperature. The shortest development time (egg to adult), 7 days, is achieved at 28 °C. Thomas Hunt Morgan began using fruit flies in experimental studies of heredity at Columbia University in 1910. His laboratory was located on the top floor of Schermerhorn Hall, which became known as the Fly Room. The Fly Room was cramped with eight desks, each occupied by students and their experiments. They started off experiments using milk bottles to rear the fruit flies and handheld lenses for observing their traits. The lenses were later replaced by microscopes, which enhanced their observations. The Fly Room was the source of some of the most important research in the history of biology. Morgan and his students eventually elucidated many basic principles of heredity.

12. T2 phage

13. Molecular genetics 1 • Although genes were known to exist on chromosomes, chromosomes are composed of both protein and DNA—scientists did not know which of these is responsible for inheritance. In 1928, Frederick Griffith discovered the phenomenon of transformation: dead bacteria could transfer genetic material to "transform" other still-living bacteria. Sixteen years later in1944, Avery, McLeod and McCarty identified the molecule responsible for transformation as DNA. The Hershey-Chase experiment in 1952 also showed that DNA (rather than protein) is the genetic material of the viruses that infect bacteria, providing further evidence that DNA is the molecule responsible for inheritance.

14. Molecular Genetics 2 Watson and Crick determined the structure of DNA in 1953, using the X-ray crystallography work of Rosalind Franklin and Maurice Wilkins that indicated DNA had a helical structure (i.e., shaped like a corkscrew). Their double-helix model had two strands of DNA with the nucleotides pointing inward, each matching a complementary nucleotide on the other strand to form what looks like rungs on a twisted ladder. This structure showed that genetic information exists in the sequence of nucleotides on each strand of DNA. The structure also suggested a simple method for duplication: if the strands are separated, new partner strands can be reconstructed for each based on the sequence of the old strand.

15. Genetic Code discovery The Crick, Brenner et al. experiment was the first to demonstrate that codons consist of three DNA bases.  Marshall Nirenberg and Heinrich J. Matthai were the first to elucidate the nature of a codon in 1961 at the National Institutes of Health. They used a cell-free system to translate a poly-uracil RNA sequence (i.e., UUUUU...) and discovered that the polypeptide that they had synthesized consisted of only the amino acid phenylalanine. They thereby deduced that the codon UUU specified the amino acid phenylalanine. This was followed by experiments in Severo Ochoa's laboratory that demonstrated that the poly-adenine RNA sequence (AAAAA...) coded for the polypeptide poly-lysineand that the poly-cytosine RNA sequence (CCCCC...) coded for the polypeptide poly-proline. Therefore the codon AAA specified the amino acid lysine, and the codon CCC specified the amino acid proline. Using different copolymers most of the remaining codons were then determined.

16. Jacques Monod • In 1971 two works appeared that created roadblocks for new theories of the origin of life. • Monod wrote a book “Chance and Necessity”. • He first created a problem by stating that organisms have purpose or “teleonomy”. He then stated that variation had to arise on top of a stationary state. • He also pointed to the chicken and egg situation between genes and enzymes. He found that he had boxed himself into an arguement in which life could have only arisen by an impossibly rare event.

17. Issues • Eigen did not accept Monod’s view of the rarity of life, but somehow imagined that a hypercycle would develop spontaneously! • Such a view was followed by Stuart Kauffmann, who imagined that the occasional rare event permitted by thermodynamics could be quite common. ( As with Bill Clinton’s comment, he failed to bring arithmetic to the problem.)

18. Manfred Eigen 1 Eigen wrote a very long paper “Self-organization of Matter and the origin of biological macromolecules” Eigen argued that “we would not attribute the attribute of being alive to anything less than the hypercycle in part VI which is characterized by ten properties. Three are metabolism, reproduction and mutability. The other 7 are associated with the chicken and egg aspects, and a cycle of enzymatic behavior which he called a hypercycle.

19. Eigen 2 At the start of the paper, Eigen asks ‘ Which came first, the protein or the nucleic acid?” And the words protein and nucleic acid may be replaced by function and information. He then states “This is absurd, because function cannot occur in an organized manner unless information is present, and this information only acquires its meaning through the function for which it encodes.”

20. Christian De Duve 1 • Following this, in 1995 De Duve wrote “Vital Dust” In which he argued that since there are a relatively small number of molecules involved in life, and they are made by common paths, life should be easy to create. • He ignored the ultra low probability of creating an exact sequence of amino acids in a protein. • E.g. with 20 amino acids, an exact string of 100 Would have a probability of 20-100 , or 10-300.

21. De Duve 2 • In a later book, Singularities , De Duve gets into his own chicken and egg problem. First he quotes Leslie Orgel saying that enzyme metabolism being totally different than pre-enzyme metabolism, could shed no light on the original metabolism. • He then has a problem as to how enzyme metabolism could arise.

22. Hoyle • Hoyle also looked at the probability of making a single simple prokaryote, and decided that it was similar to a tornado travelling through a junk-yard and creating a Boeing airliner complete and working!

23. What went wrong? 1) A process of survival of a mutable material in a dissipative environment MAY create a survival line of it may not. 2) If a survival line is created, mutable materials will change roles as well as forms. 3) The first survival state does not need to employ efficient reactions, it merely needs to grow faster than it is destroyed. 4) Therefore Eigen is wrong.

25. Variations 1 Soup is not alive. 2 Play the movie backwards as far as replanting the potatoes and carrots in the yard - this corresponds to creating life. 3 Play the movie forward and keep the soup on the heat without adding water. The black stuff produced is called “tar” or “kerogen”.

26. Conclusion The recipe for life not only requires the ingredients. It also has issues of how and when ingredients are added, the quantities that are added. The storage of ingredients. The rate and form in which energy is added, and the nature of pauses where the less fit fail to survive. Life is not a foregone conclusion. From the statistics of 1 planet, and it has life, the probability of a planet having life is: 1 +/- 1 !