Genetica per Scienze Naturalia.a. 08-09 prof S. Presciuttini

This document is licensed under the

Attribution-NonCommercial-ShareAlike 2.5 Italy license, available at

http://creativecommons.org/licenses/by-nc-sa/2.5/it/http://creativecommons.org/licenses/by-nc-sa/2.5/it/

MAJOR ADVANCES IN GENETICS

Genetica per Scienze Naturalia.a. 08-09 prof S. Presciuttini

1. The laws of inheritance 1866: Gregor Mendel publishes his findings on the laws of 1866: Gregor Mendel publishes his findings on the laws of

inheritance based on experiments with pea plants. He inheritance based on experiments with pea plants. He develops three “principles”: develops three “principles”: Dominance, Segregation, and Dominance, Segregation, and Independent AssortmentIndependent Assortment

DominanceDominance each inherited characteristic is determined by two alternative hereditary factors, each inherited characteristic is determined by two alternative hereditary factors,

and one factor is dominant over the other.and one factor is dominant over the other. SegregationSegregation

the sex cell of a plant or animal may contain one factor (allele) for different the sex cell of a plant or animal may contain one factor (allele) for different traits but not both factors needed to express the traits. traits but not both factors needed to express the traits.

Independent assortmentIndependent assortment Different characteristics are inherited independently from each other. Different characteristics are inherited independently from each other.

Genetica per Scienze Naturalia.a. 08-09 prof S. Presciuttini

2. Before the “rediscovery”

1882: german biologist Walter Flemming, by staining 1882: german biologist Walter Flemming, by staining cells with dyes, discovers rod-shaped bodies he calls cells with dyes, discovers rod-shaped bodies he calls ""chromosomeschromosomes.“ .“ He makes the first accurate counts He makes the first accurate counts of chromosome numbers and accurately drew the of chromosome numbers and accurately drew the "longitudinal splitting" of chromosomes."longitudinal splitting" of chromosomes.

1871: Johann Friedrich Miescher isolates a substance 1871: Johann Friedrich Miescher isolates a substance which he calls which he calls NUCLEINNUCLEIN from the nuclei of white from the nuclei of white blood cells that was soluble in alkalis but not in acids. blood cells that was soluble in alkalis but not in acids. This substance came to be known as This substance came to be known as nucleic acidnucleic acid..

Genetica per Scienze Naturalia.a. 08-09 prof S. Presciuttini

3. The rediscovery of Mendel’s work

by the German by the German botanist Carl botanist Carl Correns,Correns,

the Dutch the Dutch botanist Hugo botanist Hugo De Vries,De Vries,

and the Austrian and the Austrian agronomist Erich agronomist Erich von Tschermak.von Tschermak.

Mendel’s laws of inheritance are rediscovered in 1900, Mendel’s laws of inheritance are rediscovered in 1900,

Genetica per Scienze Naturalia.a. 08-09 prof S. Presciuttini

4. Where do genes reside?In 1902, Walter Sutton (an American who at the time was a graduate student) and Theodor Boveri (a German biologist) recognized independently that the behavior of Mendel's particles during the production of gametes in peas precisely parallels the behavior of chromosomes at meiosis:

1) genes are in pairs (so are chromosomes);

2) the alleles of a gene segregate equally into gametes (so do the members of a pair of homologous chromosomes);

3) different genes act independently (so do different chromosome pairs).

After recognizing this parallel behavior, both investigators reached the same conclusion that the parallel behavior of genes and chromosomes suggests that genes are located on chromosomes.

Genetica per Scienze Naturalia.a. 08-09 prof S. Presciuttini

5. The word GENETICS is formulated

1909: Danish botanist Wilhelm Johannsen proposes the 1909: Danish botanist Wilhelm Johannsen proposes the term "term "genegene" (from the Greek word "genos" which means " (from the Greek word "genos" which means "birth") to refer to a Mendelian hereditary factor. "birth") to refer to a Mendelian hereditary factor. Johannsen also proposes two terms, Johannsen also proposes two terms, genotypegenotype and and phenotypephenotype, to distinguish between one's genetic make-up , to distinguish between one's genetic make-up and one's outward appearance.and one's outward appearance.

1903: William Bateson coins the terms 1903: William Bateson coins the terms geneticsgenetics, , FF11, , FF22, , Allelomorph (later shortened to Allelomorph (later shortened to alleleallele), ), homozygotehomozygote, , heterozygoteheterozygote, and , and epistasisepistasis..

Genetica per Scienze Naturalia.a. 08-09 prof S. Presciuttini

6. Genes are lined-up on chromosomes 1915: Thomas Hunt Morgan, an American geneticist, 1915: Thomas Hunt Morgan, an American geneticist,

publishes The Mechanism of Mendelian Heredity, in publishes The Mechanism of Mendelian Heredity, in which he presents results from experiments with fruit which he presents results from experiments with fruit flies that prove flies that prove genes are lined up along genes are lined up along chromosomeschromosomes. He also describes the principle of . He also describes the principle of ""linkagelinkage" — that alleles located relatively close to one " — that alleles located relatively close to one another on a chromosome tend to be inherited together. another on a chromosome tend to be inherited together.

By studying the frequency with which traits are inherited together, By studying the frequency with which traits are inherited together, Morgan and co-workers create a "Morgan and co-workers create a "genetic mapgenetic map" of fruit fly " of fruit fly chromosomes showing the relative locations of the genes responsible chromosomes showing the relative locations of the genes responsible for dozens of traits, along with approximate distances between them for dozens of traits, along with approximate distances between them on the chromosome. This work establishes the basis for gene mapping on the chromosome. This work establishes the basis for gene mapping principles still used today.principles still used today.

Genetica per Scienze Naturalia.a. 08-09 prof S. Presciuttini

7. Genes may cause quantitative variation

1918: R.A. Fisher shows that continuous traits 1918: R.A. Fisher shows that continuous traits can be explained by Mendelian segregation of can be explained by Mendelian segregation of genes: Mendel’s laws give basis for genes: Mendel’s laws give basis for statistical statistical relationships between parents and relationships between parents and offspringoffspring..

His work reconciled the Darwinian view of His work reconciled the Darwinian view of evolution with the findings of the geneticists, evolution with the findings of the geneticists, posing the basis of the so-called “Modern posing the basis of the so-called “Modern Synthesis”Synthesis”

Genetica per Scienze Naturalia.a. 08-09 prof S. Presciuttini

8. The first mutagenic agent In 1927 Herman Muller reported that X In 1927 Herman Muller reported that X

rays could induce rays could induce mutationsmutations in male fruit in male fruit flies. In his investigations Muller found flies. In his investigations Muller found that the mutation rate among the male that the mutation rate among the male fruit flies was fruit flies was linearly related to the linearly related to the radiation doseradiation dose. .

His results supplied the first experimental His results supplied the first experimental evidence of a mutagen, in this case, the X evidence of a mutagen, in this case, the X rays. Muller's work on mutation induction rays. Muller's work on mutation induction opened the door to the genetic technique opened the door to the genetic technique of using mutations to dissect biological of using mutations to dissect biological processes, which is still used extensively processes, which is still used extensively todaytoday

Genetica per Scienze Naturalia.a. 08-09 prof S. Presciuttini

9. The one-gene one-enzyme theory

• In 1941 G. W. Beadle and E. L. In 1941 G. W. Beadle and E. L. Tatum publish their classic study Tatum publish their classic study on the biochemical genetics of on the biochemical genetics of Neurospora and promulgate the Neurospora and promulgate the one-gene, one-enzyme theory.one-gene, one-enzyme theory.

• They provide the experimental They provide the experimental proof of a theory that has been proof of a theory that has been proposed by Garrod more than 30 proposed by Garrod more than 30 years beforeyears before

Genetica per Scienze Naturalia.a. 08-09 prof S. Presciuttini

10. Genes are made of DNA

In 1952 A. D. Hershey and M. Chase demonstrate that the In 1952 A. D. Hershey and M. Chase demonstrate that the DNA of phage enters the host, whereas most of the DNA of phage enters the host, whereas most of the protein remains behind.protein remains behind.

In 1953 J. D. Watson and F. H. C. Crick propose a model for DNA In 1953 J. D. Watson and F. H. C. Crick propose a model for DNA comprised of two helically intertwined chains tied together by comprised of two helically intertwined chains tied together by hydrogen bonds between the purines and the pyrimidines.hydrogen bonds between the purines and the pyrimidines.

In 1944 O.T. Avery identifies deoxyribonucleic acid (DNA) as the In 1944 O.T. Avery identifies deoxyribonucleic acid (DNA) as the "transforming principle“. DNA extracted from dead pneumonia bacteria of "transforming principle“. DNA extracted from dead pneumonia bacteria of a strain lethal to mice was capable of inducing virulence (lethality) in live a strain lethal to mice was capable of inducing virulence (lethality) in live but previously harmless strainsbut previously harmless strains

Genetica per Scienze Naturalia.a. 08-09 prof S. Presciuttini

11. Genes are regulated in their expression• 1961 F. Jacob and J. Monod publish

"Genetic regulatory mechanisms in the synthesis of proteins," a paper in which the theory of the OPERON is developed.

• They found that the sugar glucose suppressed E. coli's ability to use other sugars, specifically the milk sugar lactose. When glucose was present, it was used it first. Only after the glucose had been consumed was lactose used. Intriguingly, there was "lag" between when glucose was used up and the bacteria started to grow on lactose.

                       

Francois Jacob

Jaques Monod

Genetica per Scienze Naturalia.a. 08-09 prof S. Presciuttini

12. The birth of genetic engineeringIn 1972 Paul Berg creates the first recombinant DNA molecules, In 1972 Paul Berg creates the first recombinant DNA molecules, combining in a single DNA molecule genes from different combining in a single DNA molecule genes from different organisms.organisms.

Results of his experiments, published in 1972, represented crucial Results of his experiments, published in 1972, represented crucial steps in the subsequent development of genetic engineering. By his steps in the subsequent development of genetic engineering. By his methods, individual genes could be isolated and inserted into methods, individual genes could be isolated and inserted into mammalian cells or into such rapidly growing organisms as mammalian cells or into such rapidly growing organisms as bacteria. The genes themselves could then be studied, and their bacteria. The genes themselves could then be studied, and their protein products expressed and even manufactured in quantity. protein products expressed and even manufactured in quantity.

The prospect of recombinant DNA emerged from a series of advances in biochemistryThe prospect of recombinant DNA emerged from a series of advances in biochemistry—most especially, from discoveries of new enzymes. Particularly important were the —most especially, from discoveries of new enzymes. Particularly important were the restriction enzymes that act as "scissors" to cut molecules of DNA at specific points. restriction enzymes that act as "scissors" to cut molecules of DNA at specific points. Similarly, ligases are enzymes that forge covalent bonds. The discovery of DNA ligase Similarly, ligases are enzymes that forge covalent bonds. The discovery of DNA ligase provided a kind of chemical soldering that could restore DNA after a foreign gene was provided a kind of chemical soldering that could restore DNA after a foreign gene was spliced into it. These and other enzymes, captured from nature, could be used as tools spliced into it. These and other enzymes, captured from nature, could be used as tools in genetic engineering.in genetic engineering.

Genetica per Scienze Naturalia.a. 08-09 prof S. Presciuttini

13. Genes can be sequencedIn 1977 Walter Gilbert and Frederick Sanger devise techniques for In 1977 Walter Gilbert and Frederick Sanger devise techniques for sequencing DNAsequencing DNA

Molecular biologists by the 1970s had deciphered the genetic code Molecular biologists by the 1970s had deciphered the genetic code and could spell out the sequence of amino acids in proteins. But and could spell out the sequence of amino acids in proteins. But inability to easily read off the precise nucleotide sequences of DNA inability to easily read off the precise nucleotide sequences of DNA forestalled further advances in molecular genetics and all prospects of forestalled further advances in molecular genetics and all prospects of genetic engineering. Walter Gilbert (with graduate student Allan M. genetic engineering. Walter Gilbert (with graduate student Allan M. Maxam) and Frederick Sanger, in 1977, working separately in the Maxam) and Frederick Sanger, in 1977, working separately in the United States and England, developed new techniques for rapid DNA United States and England, developed new techniques for rapid DNA sequencing. sequencing.

Sanger and Gilbert each took advantage of recently Sanger and Gilbert each took advantage of recently discovered enzymes and both methods benefited from discovered enzymes and both methods benefited from improvements in gel electrophoresis, a method used for improvements in gel electrophoresis, a method used for imaging the order of nucleotides.imaging the order of nucleotides.

Walter Gilbert

Fred Sanger

Genetica per Scienze Naturalia.a. 08-09 prof S. Presciuttini

14. A prodigious new technique

In 1983 Kary Mullis conceives and helps develop polymerase chain reaction (PCR), a technology for rapidly multiplying fragments of DNA. The process is hailed as one of the monumental scientific techniques of the twentieth century; PCR multiplies a single, microscopic strand of the genetic material billions of times within hours.This invention would again revolutionize biotechnology and make the Human Genome Project possible.

Genetica per Scienze Naturalia.a. 08-09 prof S. Presciuttini

15. The genome era1995: The first completely sequenced genome of a self-replicating, free-living 1995: The first completely sequenced genome of a self-replicating, free-living organism—the bacteria Haemophilus influenzaeorganism—the bacteria Haemophilus influenzae

1996: Some 600 scientists around the world finished sequencing the genome of the 1996: Some 600 scientists around the world finished sequencing the genome of the yeast S. cerevisiae.yeast S. cerevisiae.

1998: A microscopic worm commonly used in genetic studies was the first 1998: A microscopic worm commonly used in genetic studies was the first multicellular organism to have its genome sequenced. The worm, called Caenorhabditis multicellular organism to have its genome sequenced. The worm, called Caenorhabditis elegans, lives in soil and grows to be a millimeter in length.elegans, lives in soil and grows to be a millimeter in length.

1999: Drosophila's entire genome was sequenced and assembled by Celera Genomics, 1999: Drosophila's entire genome was sequenced and assembled by Celera Genomics, in conjunction with the federally funded Berkeley Drosophila Genome Project in conjunction with the federally funded Berkeley Drosophila Genome Project (BDGP), in the course of about eight months.(BDGP), in the course of about eight months.

2000: On June 26, 2000, Celera Genomics' and the International Human Genome 2000: On June 26, 2000, Celera Genomics' and the International Human Genome Project made a joint announcement they had finished a "working draft" of the genome Project made a joint announcement they had finished a "working draft" of the genome at the White House in the United States, during a major news event to mark an historic at the White House in the United States, during a major news event to mark an historic milestone.milestone.