Title of the exhibition: T. H. Morgan – Great Experiments on Little Flies
Opening: 12.10.2010, 5 p.m.
Duration: 12. 10. 2010 – 31. 01. 2011
Author of the exhibition: Prof. RNDr. Jiřina Relichová, CSc.
The Mendel Museum of Masaryk University has prepared an exhibition that remembers the 100th anniversary of the discoveries of American scientist Thomas Hunt Morgan. He was awarded the 1933 Nobel Prize as the first geneticist in history. He did the experiments on fruit flies with his team. Through his work and research, Morgan motivated generations of his colleagues and successors in his office known as the “fly-room.” He was among the first ones who had confirmed the correctness of Mendel`s experiments on the garden pea.
This exhibition is the only exhibition, not only in Europe, but also in the world, which commemorates this significant anniversary. It is supplemented with work sheets and computer programs. There are Morgan`s original notes as well. The exhibition was created in cooperation with the archives of the California Institute of Technology, where Morgan had worked in 1930s and 1940s. Other partners of the exhibition are Biomania o.s., GSGM and the South Moravian Region.
Exhibition „T. H. Morgan – Great Experiments on Little Flies”
Genetics in the second half of the 19th century
Gregor Mendel discovered the basic laws of heredity
Charles Darwin formulated the theory of evolution of animal species
The theory of evolution of the organism from one cell was semi-finished
Inception of genetics...
The inception of genetics begins unwittingly in the past. Since long ago people cultivated plants and bred animals. They selected only the strongest, fastest or most resistant specimen. These specimens were crossed with each other and the new variants of plants and animals were created. Even though the methods of cultivating were reaching huge success over the course of years and centuries, nobody had surmised how these unique and advantageous characters are inherited from parents to offspring. There was a huge turning point in 1865 when Gregor Mendel presented the results of his experiments with garden pea in Brno, Czech Republic. He formulated the basic principles and laws of heredity. These lectures were published a year later in the almanac of the Natural History Society as Versuche über Pflanzen-Hybriden (Experiments in plant hybridization). Mendel`s experiments and results remained misunderstood. Not until 1900 three scientists – Erich von Tschermak, Carl Correns and Hugo de Vries – independently from each other get the same results as Mendel. Mendel did get the credit posthumously and was entitled “The father of genetics”.
The genetics as a branch of knowledge dates back in 1900. The word “Genetics” was used for the first time in 1906 by William Bateson. At the beginning of the last century the development of this new field of science was very vehement. Thomas Hunt Morgan had the main merit in this. Together with his co-workers he had explained Mendel`s genetics on the basis of the existence of chromosomes and genes. He had summarized his first fundamental discoveries in his works about the research with fruit flies Drosophila melanogaster published in Science magazine in 1910 and 1911. The discoveries were: the genes take place on chromosomes, every gene takes place on a particular chromosome, the character for drosophila`s eye color takes place on a sex chromosome X in the locus for eye color. Thomas Hunt Morgan was awarded the 1933 Nobel Prize as the first geneticist in history.
... and its further development
There were the experiments done between years 1928 and 1944 to find the substance which carries the genetics information. In 1944 was proofed that this substance is a DNA. The DNA structure was discovered in 1953 and Francis Crick, James Watson and Maurice Wilkins were awarded the 1962 Nobel Prize. There was a boom of a research and knowledge since that time. Another field of study came into being in addition to a classic genetics - it was the molecular biology. Today the genomics and primarily the proteomics are getting to the forefront. Because there was a huge amount of scientific discoveries in these disciplines, here is only a brief list:
1958 – Central Dogma of the Molecular Biology was articulated
1960 – Discovery of one of the RNA types – a so-called messenger RNA and the evidence of its function
1691 – Messenger RNA used for deciphering the genetic code
1966 – Complete solving of genetic code
1973 – Beginning of cloning genes - the foundation of genetic engineering
1977 – Compound gene discovery
1977 – Introduction of sequencing methods, or “reading” of the DNA
1981 – Discovery of a specific character of the RNA (so-called catalytic activity)
1982 – Commercial production of human insulin from a bacteria
1983 – Beginning of sequencing genomes from the model organisms
1983 – Discovery of the polymerase chain reaction (PCR)
2003 – 99,9 % of the human genome sequences read
Levels of DNA Folding
Cell – Nucleus – Set of Chromosomes – Nucleosomes – Double Helix – Nucleotide
Cell – the basic structural part of an organism, there is about 1014 of them in the human body
Nucleus - the main part of most of the eukaryotic cells. There is the genetic information kept in the nucleus. This information is in a shape of the slim fibers of chromosomes which are in this stage called the chromatin fibers. During the course of the cell division (mitosis) the DNA shrinks and creates the typical condensed and twisted elements – chromosomes.
Chromosome – the structure of a chromosome is made not only of the DNA, but also of the proteins and other substances. There is a centromere in the middle which keeps two affiliated fibers together (so-called chromatids). This place is very important for the correct division of the chromatids within a cell division. The number of chromosomes is individual for every organism.
Nucleosomes – the ellipsoidal elements around which the DNA fibers are wrapped. It is compound from proteins called the histones. If you look on the DNA in this balled stage under the electronic microscope, you will see a structure which looks like a string of beads.
Double Helix – a geometric figure made of two complementary fibers which mutually turn around themselves.
Nucleotide – the basic subunit of a nucleic acid. Every nucleotide is made of a phosphate group, a sugar – pentose and a nitrogenous base. The bases make pairs together. That is how the particular fibers of Double Helix keep up together. Within the DNA the adenine base makes always a pair with the thymine and guanine with cytosine. The phosphate group together with pentose makes a so-called sugar-phosphate skeleton which turns around the perimeter of DNA.
In front of the Fly Room
As written above Thomas Hunt Morgan was a very important scientist in a field of genetics at the beginning of the 20th century. He worked at a Columbia University in the City of New York. The main experimental organism that he worked with was a fly Drosophila melanogaster. The laboratory in which was the experiments done was soon known as a “Fly Room”.
This room was not very huge, it measured 5 x 7 meters and there were 8 tables in it. There were bunches of bananas hanging in the corner which were used as a food for Drosophila. There were many vials on shelves illuminated with electric bulbs. The vials were mostly the milk bottles in which the flies were bred.
There were plenty of domestic and foreign students, inceptors and post-doctoral students in this room. They all together created a group where everybody did his own experiments but they also knew what did the others. Every new result was openly discussed with others. There was an atmosphere of endless enthusiasm and excitement. The main thing was that the research should continue.
There were numerous populations of drosophila in the Fly Room in that time. Morgan searched in the thousands of drosophila for the individual which will be evidently different in one of the characters from standard individuals. He was not successful for a long period of time, but his persistence brought fruit. On April 1910 Morgan found in one bottle with plenty of drosophila one male with white eyes, different from others with red eyes. Thus Morgan discovered a spontaneous mutant in the gene encoding for the eye color. One of his most important discoveries came up from this one fly.
“You can now go and see the whole Fly room. Do not be afraid and enter. You can become a worthy scientist for a while. Familiarize yourself with a work in a laboratory.”
Model organisms – what are they good for?
First scientists who were engaged in genetic experiments used commonly spread and simply accessible plants or animals. Beans, peas or birds were the most favoured. The scientists later discovered that some organisms are more suitable for these experiments, that the breeding and cultivation is better, that the conditions for living were not demanding and that the reproduction is faster and the number of offspring is bigger. All these characters made the work easy for scientists. Nowadays there is a complex of several carefully chosen animals, plants and microbes often used for genetic experiments. These organisms are named as model organisms.
As written above the model organism has to fulfill several basic conditions. First of all it must have a short life cycle, have a large number of offspring and the cultivating and breeding must be economically and practically undemanding. The possibility of doing controlled crossing is also important, it means that two individuals with desired characters are deliberately mutually fertilized.
It is possible to follow specific characters thanks to these organisms relevant to complex genome or particular chromosomes of the organism given. It is possible to determine a number, a shape or structures of these chromosomes. It is also possible to get on a level of genes within the methods of a molecular biology and follow the production and the function of its proteins made by the particular organism. The information obtained in this way is used for description of universal phenomenon and for derivation of characters and relationships valid for other organisms including a human. For example many proteins located in a human body were primarily described at yeast. Identically the principle of sex chromosome gene heredity, of different organisms including a human, was explained with crossing of a little fly – drosophila.
The most popular model organisms in genetics and molecular biology nowadays are:
Escherichia coli – a microbe, prokaryotic organism
Saccharomyces cerevisiae – brewer`s yeast, unicellular eukaryotic organism
Caenorhabditis elegans – a nematode, multicellular eukaryotic organism
Arabidopsis thaliana – a thale cress, a representative of plants
Drosophila melanogaster – a fruit fly, a representative of insect
Fugu rubripes – a representative of fish
Mus musculus – the house mouse, a representative of mammals
Drosophila is a representative of insect known by the majority of people from their own homes. If you leave somewhere maturing fruit the drosophila – also known as fruit or vinegar flies - will appear soon. Males grow up 2 or 3 millimeters, females are a little bit bigger. The original standard type (sometimes a word wild is used) has umber or rarely black body. It has straight wings and red eyes. Today a huge number of mutant types is known which have different shape of wings, body color, eye color or others. Drosophila originated in tropic areas, but due to the activity of humans it expanded the whole world. So today we can find them all around the world maybe except Antarctica. Its main livelihood is usually decomposed fruit, mushrooms or plants. The lifecycle of Drosophila contains four main stages of development: egg, grub, cocoon and imago (adult). The transformation from egg fertilization to imago lasts about 10 days.
The number of Drosophila`s chromosomes was described correctly for the first time in 1908 by Stevens, but only in female`s case. For males she stated that its research is difficult and that its chromosome X is probably connected with autosome and that it has not chromosome Y. Only in 1914 thanks to cytological studies the correct number of Drosophila`s chromosomes was found out by scientists Bridges and Metz. It was the proof that drosophila has 4 pairs of chromosomes: 3 pairs of autosome and 1 pair of sex chromosome.
Human vs Drosophila
Number of chromosomes 46 vs 8
Size of the genome 3000 Mb vs 120 Mb
Life cycle years vs 10 days
Number of offspring maximum 20 vs hundreds
Possibility of pointed crossing no vs yes
Number of genes c. 20 000 vs c. 13 600
Male or female?
The human`s sex is determined by a presence of the chromosome Y and the SRY gene which takes place on this chromosome. The product of this gene – a so-called Testis-determining factor – cause that the human embryo develops to a man`s sex. That means that even though the individual has for example two chromosomes X and one functional chromosome Y the individual will be a male. If the individual will not have the chromosome Y with SRY gene – it will be a female.
Drosophila has a different principle of sex determination. It is primarily determined by the ratio between the number of chromosomes X and the set of autosomes (X:A). The male individuals without genetic irregularities have the ratio 0,5 (that means 1 chromosome X : 2 sets of autosomes). The female individuals have the ratio 1,0 (2 chromosomes X : 2 sets of autosomes).
The significance of drosophila in a modern research
Other scientists were continuing in the research of drosophila after Morgan. It proved to be an ideal experimental model organism. Firstly the spontaneously found mutants were searched in the artificial breeding. But in the thirties the scientists started to create mutants on their own. The effect of x-radiation was used previously, later were used the chemical substances which damaged the DNA molecules and changes the genes. There were born flies without eyes, with two pairs of wings, with legs on head or eyes on wings. That was how it was possible to learn the function of genes and understand the mechanisms that secure the proper/regular/correct evolution of organs.
One hundred years have passed from its establishment and the fruit fly is still one of the most favourite models and has a significant importance for up-to-date biomedical research. Approximately 60% of its genes have “relatives” among human genes. If we follow its functions in fly`s body, we can learn more about ourselves.
Drosophila is used as a model for study of various complex diseases such as diabetes, parkinsonism, Alzheimer`s Disease, Spinal muscular atrophy, Duchenne muscular dystrophy and others. Many drosophila`s genes are similar to human`s genes. The mutations of these genes causes a cancer, neurologic diseases, metabolic diseases or inborn evolutional defects. It is because the complex diseases as cancer have its origin in regulation defects, growth control defects, evolutional defects and defects in distinction of cells. These processes are similar in many ways throughout the genotypes including drosophila and human.
The example which proves that the significance of drosophila as a model for studying cancer in up-to-date research is huge is: the scientists with the assistance of drosophila investigated the roots of Tuberous sclerosis. It is a hereditary disease connected with brain, lungs, skin and kidney tumors. Even though many years ago was found out that this disease is caused by mutation in two genes Tuberous sclerosis complex 1 and 2 (TSC1 and TSC2), nobody knew anything about its function. That is why there was no cure. The problem of human`s illnesses is that we usually see only the consequences. Now we know which mutations causes the human illnesses, so we can induce the drosophila`s mutations unnaturally and follow its development from the beginning to the end of the disease.
The latest experiments with drosophila shows that TSC1 and TSC2 genes are connected with the signaling pathway for growth and tissue`s size regulation. The follow-up research showed that blocking the activity of one particular gene leads to a defect remedy. This gene is called S6kinase and is also connected with the same signaling pathway as his superordinate mutate genes TSC1 and TSC2. It is the first step which can lead to the cure of this hereditary illness.
Other scientists found out that complicated neurological diseases (like parkinsonism, Alzheimer`s Disease and Huntington Disease) and mental diseases (like schizophrenia and autism) have the same characteristics notably related to the function mechanisms of the central nervous system and a specific signal transfer. The discovery of these mechanisms is successful because of Drosophila. Even though it is clear that the brain of human and drosophila is completely different, the basic function mechanisms and its genes are almost similar. Today scientists can take out drosophila`s brain and study under the microscope the differences between neuron reactions of normal and mutant flies.
The most of the neurologic diseases shows in the higher age of the patient. So the short generation period of drosophila is a big advantage. For example in comparison with rats the scientists need to wait months for results but only days in case of drosophila. Some substances developed on the basis of drosophila research was successfully used in the clinical practice, mainly to reduce the symptoms of Alzheimer`s and Parkinson`s diseases.
Thomas Hunt Morgan (25.9.1866 – 4.12.1945)
Thomas Hunt Morgan was born on 25th September 1866 to the prominent southerner family. He studied biology with a view to morphology and physiology at the university. He obtained the Ph.D. degree on Johns Hopkins University in Baltimore, Maryland in 1860 as a 24-year-old for the work about invertebrate sea animals. In 1891 he accepted the post of a professor in Bryn Mawr College. He was interested in experimental embryology there. He studied the regeneration of earthworms and the development of sea urchins and frogs. In 1904 he was offered a recently established position of a professor of experimental zoology at Columbia University in New York. Morgan accepted this offer. The University of Columbia was established in 1745 and is the oldest institution of higher education in the state of New York and the 5th oldest in USA. Interesting thing is that from 1901, when was the first Nobel prize awarding, 79 university`s graduates obtained this prize.
Edwin Wilson, Morgan`s long-time friend and colleague, influenced Morgan`s research direction. Wilson was an excellent cytologist and founder of the branch of cell biology. Wilson persuaded Morgan to start the heredity research, because he considered it as a key to understanding the evolution – how a sperm and an egg traject the parent`s characters to offspring and how one single cell (the fertilized egg) give a life to an animal which carries these characters and passes it to next generations.
Approximately in 1909 Morgan turned over his attention from evolutionary biology to genetics and started to use Drosophila melanogaster as the experimental model. The Drosophila was probably recommended by W. E. Castle, who was professor of zoology at Harvard University. Morgan soon recognized the excellent characters of Drosophila as modern organism and was convinced that it could be a suitable model for an evolution study.
Morgan moved as a 62-year-old in the Califorina Institute of Technology (CALTECH) where he established a new laboratory of experimental genetics. Many colleagues and students followed him. Caltech is a private university focused on the science, technology and engineering research in Pasadena, USA. Morgan worked at this university till the end of his life in 1945.
Morgan as a person was very passionate for scientific research and passed his own keenness on his co-workers. He was generous and had a very good sense of humor. He was not prejudiced and had a strong critical attitude to the results. He providently established a new approach to a scientific research based not on a subordination according to an age as it was until the moment, but based on the democratic principles where the main things were a asset of ideas and the value of results. That was for example reflected in the fact that students addressed their professors by forenames, which was very surprising for visitors.
One of the most important contributions of T. H. Morgan to these discoveries was not in fact scientific. It was a unique creative atmosphere which he created successfully. There was a noble and generous climate and the exchange of ideas and results were the highest value. In 1909 Morgan presented his basic lecture about zoology to pregraduate students in Columbia. C. B. Bridges and A. H. Sturtevant were among these students. They took a real interest in this lecture and were very happy when Morgan employed them in his laboratory. It was the time when the genetic study of drosophila started and the above mentioned student were on the right time in the right place. H. J. Muller was among other students who graduated as a physiologist at Columbia in 1910. He intensively joined the drosphila experiments. T. H. Morgan was awarded the 1933 Nobel Prize for discovery the role of chromosomes in heredity as the first geneticist in history. He shared the reward with his co-workers Sturtevant and Bridges.
Morgan`s experiments and research
The heredity of characters bound in sex chromosomes
Morgan did several classic experiments with drosophila crossing and the observed character was the eye color. Morgan firstly crossed a white-eyed male with a red-eyed female. There were 1237 individuals in the offspring with red eyes only. He crossed these individuals with each other. In the next generation there were only eyed females, but males had both red and white eyes in 1:1 ratio. Later when he used the reciprocity crossing (that means he used a red-eyed male and a white-eyed female) the offspring showed the so-called cross heredity – sons carried mother`s characters and daughters carried father`s characters. From the results Morgan deduced that the gene responsible for eye color must lie on one of the sex chromosomes. The organ`s discovery that genes take place on chromosomes was by important for Mendel`s discovery, because it offered a mechanism for explanation of Mendel`s principles. Morgan was skeptical both to Mendel`s theory of heredity and Mendel`s factors at first. But when he experimented with drosophila he understood that Mendel`s “factors” could have a physical substance as genes on chromosomes and started to think of Mendel`s theory of heredity in a new light. Morgan`s students later found many other genes on sex chromosome X.
The fact that there is no identity in reciprocity crossing is other important character bound in sex chromosomes. It is very important if the carrier of the particular character is the father or the mother.
System of a genetic protocol
X, Y = sex chromosomes
Superior index w = a white mutation, the individual carries a recessive alleles for white eyes
Superior index + = a standard (wild) type, the individual carries a dominant alleles for red eyes
1. Morgan`s crossing
P: red-eyed female x white-eyed male
F1: red-eyed female, red-eyed male
F2: red-eyed female, white-eyed male, red-eyed male
(X+X+ ; X+Xw) (XwY) (X+Y)
Explanation: In this crossing there will be only red-eyed individuals in F1 generation, because the dominant allele for this character is inherited from mother. In F2 generation all females will have red eyes (the standard allele is inherited from father), while male will have white and red eyes in 1:1 ratio.
2. Morgan`s cross heredity
P: white-eyed female x white-eyed male
F1: red-eyed female, red-eyed male
F2: red-eyed and white-eyed female, red-eyed and white-eyed male
(X+Xw) (XwXw) (X+Y) (XwY)
Explanation: There is a cross heredity by F1 generation. It means that females (daughters) will inherit characters from its father and males (sons) from its mothers. In this case females will have red eyes from father and males white eyes from mother. In F2 generation will be all four phenotypes, that means red-eyed and white-eyed females and red-eyed and white-eyed males.
Bond of genes
The bond on autosomes was described by Morgan and Bridges between years 1919 – 1923 on the basis of mutations of the second and third chromosome. Sturtevant realized the first autosomal chromosomes testing on February in 1912. He discovered that the genes responsible for black color of the body and pink color of the eyes are independent on each other. He deducted that these genes probably take place on different chromosomes. On March 1912 Bridges discovered that if the new mutant with curved wings is crossed with a black individual, there will be no double mutant. That meant that there is a bond on autosomes. Soon it was clear that there is more autosomal mutants than chromosomes. Bridges and Sturtevant started with its the large crossing to find out the bound. Approximately a week before ending these experiments C.J. Lynch discovered that after crossing an individual with black body with an individual with curved wings there will be no double mutant even in F2 generation. It was a first published work about autosomal bonds of drosophila (on the second chromosome in this case). In 1912 Morgan also discovered that there is no crossing over among male`s genes. It was later generalized for genes which take place also on other chromosomes. In the same year Bridges and Sturtevant found genes of the second and third bound group. Fourth bound group was found by Muller in 1914.
It is interesting that Morgan and his co-workers allocated the gene location on chromosomes even though it wasn`t possible to observe genes on chromosomes at that time. Their thoughts were deducted only from the results of experimental crossing. But it was results of extremely wide, elegant and intensive research.
The chromosome theory
The research with D. melanogaster entered in 1915 to the situation that the research group in Columbia was ready to interpret the whole area of Mendel`s genetic in terms of chromosome theory. The milestone was the work from 1915 “The Mechanism of Mendelian Heredity” written by Morgan, Sturtevant, Muller and Bridges. There was a scepticism among geneticists to accept the interpretation of the theory of inheritance on the grounds of the chromosome theory. Even the prominent geneticists didn`t adopted these theory immediately. For example Johannsen accepted the chromosome theory only in the third publication of his book “Elemente der exakter Erblichkeitslehre” from 1926. Even Bateson was sceptic to this theory in his work “The mechanism of Mendelian heredity” from 1916, even though he admitted that the results of experiments with Drosophila are the most significant after Mendel`s experiments. At that time he considered incomprehensible that the elements of chromatin or any other substances (complicated as you pleased) could be a carrier of such potential that is genes` attribution.
The discoveries of Morgan`s co-workers
Bridges, one of Morgan`s co-workers, came to the phenomenon called nondisjunction through the cytological study. This discovery started in Morgan`s work with a bound on sex of white-eyed male drosophila. In the offspring Morgan observed the original mutant male with white eyes and several white-eyed males as well. Bridges observed further similar cases. He discovered after the cytological experiments in 1914 that females with unusual offspring have three sex chromosomes – XXY. Later he described the process of nondisjunction. He summarized his observations in his work which was published in 1916 in the first issue of newly established magazine called Genetics.
Other Morgan`s co-worker, the nineteen-year-old student of the third grade at Columbia University, Alfred Sturtevant had merit in other huge discovery. In 1913 he derived a procedure of mapping genes on chromosomes. It is used till today for all organisms including human. He included in this first chromosome map genes bound on sex, namely gene for yellow color of body (yellow), gene for eye color (white, vermilion), gene for reduced wings (miniature) and genes for rudimentary wings (rudimentary). Sturtevant published his discoveries in 1913. Together with marking out the order of genes on a chromosome Sturtevant counted the relative distances among particular genes.
The location of genes on chromosomes which was gained by Morgan`s group as a genetics (recombination) maps, was later confirmed by Morgan`s student Calvin Bridges. He used the unforseen advantage of drosophila – the case-worms have in its saliva glands chromosomes that are many times bigger than chromosomes in other body cells. These gigantic chromosomes are well seen under the microscope and thanks to its unique form – swapping of lighter and darker stripes with different width and distances – it was possible to design the physic cytogenetic map and place it accurately on particular genes.
Summary of Morgan`s discoveries
1. The abstract genetic factors (today called the genes) whose existence was predicted by G. Mendel was located on the visible structures in the cell – the genes take place on the chromosomes
2. The confirmation of Mendel`s principles of segregation and combination on the basis of the behaviour of chromosomes during cell division
3. Genes are organized liner on the chromosomes – like a string of beads
4. The sex is determined by a pair of sex chromosomes
5. Genes in the same chromosome act during the segregation into gametes unlikely than genes in different chromosomes, it embody a bond
6. The principal of recombination was discovered for genes in a bond on the basis of parts of pair chromosome exchange, so-called crossing-over – the unit of recombination was named “morgan”
7. Construction of the first gene (recombination) map of a chromosome
8. Construction of the first physical (cytogenetic) map of a chromosome
9. The genetic material is constant – the spontaneous gene mutations are rare
Morgan`s attitude to solving the problems of heredity reassumed the attitude of G. Mendel and markedly helped to transform the biology from a descriptive science based on morphology and anatomy to an experimental science which could be based on the same grounds as physics and chemistry.
The discoveries of Morgan and his co-workers set up the plan for biology in the 20th century.
Worked up by Bc. Zuzana Hanzelková
Translated by Michaela Jarkovská, DiS.
Authors of the texts used in this exhibition: RNDr. J. Relichová and Biomania