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Model organisms
- 1. Genome projects and modelorganisms
- 2. What are modelorganisms? A model organism is a species that has been widely studied, usually because it is easy to maintain and breed in a laboratory setting and has particular experimental advantages. These are non-human species that are used in the laboratory to help scientists understand biological processes. They are usually organisms that are easy to maintain and breed in a laboratory setting. They may have particularly robust embryos that are easily studied and manipulated in the lab, this is useful for scientists studying development. Or they may occupy a pivotal position in the evolutionary tree, this is useful for scientists studying evolution.
- 3. Genome projects andmodel organisms Source (Slide Share): Genome projects and model organisms, Level 3 Molecular Evolution and Bioinformatics by Jim Provan
- 4. Genome projects Completedgenomes: Eubacteria (inc. Escherichia coli, Bacillis subtilis, Haemophilus influenzae, Synechocystis PCC6803) Archaea (inc. Methanococcus jannaschii, Methanobacterium thermoautotrophium) Eukarya: Saccharomyces cerevisiae Caenorhabditis elegans Homo sapiens Arabidopsis thaliana Partially sequenced genomes e.g. Drosophila melanogaster, Fugu rubripes, Oryza sativa Source (Slide Share): Genome projects and model organisms, Level 3 Molecular Evolution and Bioinformatics by Jim Provan
- 5. Relationships between modelorganisms H. sapiens C. elegans D. melanogaster S. cerevisiae A. thaliana Methanococcus Archaeglobus Synechocystis PCC6803 B. subtilis M. genitalium M. pneumoniae B. burgdorferi H. influenzae E. coli Source (Slide Share): Genome projects and model organisms, Level 3 Molecular Evolution and Bioinformatics by Jim Provan
- 6. Eubacterial genomes: E.coli 4288 protein coding genes: Average ORF 317 amino acids Very compact: average distance between genes 118bp Numerous paralogous gene families: 38 – 45% of genes arisen through duplication Homologues: H. influenzae (1130 of 1703) Synechocystis (675 of 3168) M. jannaschii (231 of 1738) S. cerevisiae (254 of 5885) Source (Slide Share): Genome projects and model organisms, Level 3 Molecular Evolution and Bioinformatics by Jim Provan
- 7. The minimum genomeand redundancy Minimum set of genes required for survival: Replication and transcription Translation (rRNA, ribosomal proteins, tRNAs etc.) Transport proteins to derive nutrients ATP synthesis Entire pathways eliminated in Mycoplasma: Amino acid biosynthesis (1 gene vs. 68 in H. influenzae) Metabolism (44 genes vs. 228 in H. influenzae) Comparison of M. genitalium and H. influenzae has identified a minimum set of 256 genes Source (Slide Share): Genome projects and model organisms, Level 3 Molecular Evolution and Bioinformatics by Jim Provan
- 8. Fungal genomes: S.cerevisiae First completely sequenced eukaryote genome Very compact genome: Short intergenic regions Scarcity of introns Lack of repetitive sequences Strong evidence of duplication: Chromosome segments Single genes Redundancy: non-essential genes provide selective advantage Source (Slide Share): Genome projects and model organisms, Level 3 Molecular Evolution and Bioinformatics by Jim Provan
- 9. Invertebrate genomes: C.elegans Genome even less compact than yeast: One gene every 7143 bp (2155 bp in yeast) Due mainly to introns in protein coding genes Much more compact than humans (One gene every 50,000 bp) Compactness due mainly to polycistronic arrangement: Trans-splicing Co-expression and co-regulation Source (Slide Share): Genome projects and model organisms, Level 3 Molecular Evolution and Bioinformatics by Jim Provan
- 10. Mice as aModel Organism The mouse is closely related to humans with a striking similarity to us in terms of anatomy, physiology and genetics. This makes the mouse an extremely useful model organism. The sequence of the mouse genome was published in 2002. When compared with the human genome it was found that the two genomes were of similar size and almost every gene in the human genome has a counterpart in the mouse. So, the researchers have been able to develop thousands of mouse strains with mutations that mirror those seen in human genetic disease
- 11. History of Micein science In 1902, French biologist Lucien Cuénot was the first to demonstrate Mendel’s theories of inheritance by highlighting the genetics of coat colour characteristics in mice. In Harvard, William Castle began his research in the same year, buying mice from a local mouse enthusiast. Together with his student Clarence Little, Castle produced a series of important papers on the genetics of coat colour in mice. It took Clarence four years between 1909 and 1913 to create a healthy and genetically stable inbred strain.
- 12. Transgenic Mice Transgenicmice are mice that contain additional, artificially introduced genetic material in every cell. This additional genetic material either results in a gain or loss of function of a certain gene. For example, this may mean the mouse starts to produce a new protein. This allows scientists to investigate what specific genes do in the body.
- 13. Knockout Mice Knockoutmice are the result of the inactivation of a specific gene. The resulting change in the appearance, behaviour or biochemical characteristics of the mouse then gives an indication of the gene’s normal role in the mouse, and perhaps in humans. Knockout mice are produced by a technique called ‘gene targeting’. This involves ‘knocking out’ a gene sequence from the mouse genome and inserting an artificial gene sequence that has been generated in the lab.
- 14. Knockout Mice Aswith transgenic mice, gene targeting is carried out in mouse embryonic stem cells (ES cells) derived from a very early (usually male) mouse embryo. By manipulating the cells at this early stage of development, scientists aim to get the modified ES cells to contribute to the germ line, and give rise to sperm. This way the sperm can then carry the mutation and fertilise a normal egg to carry on the knocked-out genome on to the next generation. More than 4,000 genes have been ‘knocked-out’ using this method to help scientists investigate exactly what each gene’s role is in the body.
- 15. Sequencing the Micegenome Before the sequenced genome was available, looking for a gene or a mutation was like looking for a needle in a haystack. Sequencing of the mouse genome was completed in 2002, a powerful scientific tool was made available. Now, with a huge database of information available online, all that is needed are a few clicks for researchers to be able to look up specific genes and their location on the mouse chromosomes. From this we can then choose one or two areas that look the most promising to search for a mutation.
- 16. Significance of Micegenome Researchers have developed an array of mouse models to help scientists understand a whole collection of human diseases. This has been made possible by the ability to create transgenic and knockout mouse models which give scientists the means to observe the function of individual genes. The genetic similarities between mice and men means that the knowledge derived from experiments with these mice can provide invaluable insights into human biology. Being able to go back and forth between the mouse and human genomes so easily has also made it much simpler and quicker to target related human genes that could be candidates for drug development. Now, discoveries that would once have taken years can now be done in a matter of months.
- 17. Drosophila as aModel Organism The fruit fly (Drosophila melanogaster) has been extensively studied for over a century as a model organism for genetic investigations. It also has many characteristics which make it an ideal organism for the study of animal development and behavior, neurobiology, and human genetic diseases and conditions A good model organism needs to share, on the molecular level, many similar features and pathways with humans. Approximately 60% of a group of readily identified genes that are mutated, amplified, or deleted in a diverse set of human diseases have a counterpart in Drosophila
- 18. Benefits of Fruitfly The fruit fly has many practical features that allow scientists to carry out research with ease: A short life cycle, Ease of culture and maintenance, and Less number of chromosomes Small genome size (in terms of base pairs), but Giant salivary gland chromosomes, known as polytene chromosomes.
- 19. Life Cycle ofDrosophila melanogaster Image Source: Carolina Biological Supply Company
- 20. Life Cycle ofDrosophila melanogaster The female fruit fly, about 3 mm in length, will lay between 750 and 1,500 eggs in her lifetime. The life cycle of the fruit fly only takes about 12 days to complete at room temperature (25°C). After the egg (at a mere half a millimeter in length) is fertilized, the embryo emerges in ~24 hours
- 21. Genome of Drosophila As with humans, the chromosomes of Drosophila melanogaster come in pairs -- but unlike humans, which have 23 pairs of chromosomes, the fruit fly has only four: a pair of sex chromosomes (two X chromosomes for females, one X and one Y for males), together designated Chromosome 1, along with three pairs of autosomes (non-sex chromosomes) labeled 2 through 4. Chromosome 4 is the smallest and is also called the dot chromosome. It represents just ~2% of the fly genome.
- 22. The giant polytenechromosomes found in the fly's salivary glands (compared here with the chromosomes from the fly's ovary) are another characteristic that makes the fruit fly an important organism for laboratory studies. These easily visualized chromosomes provided a road map for early geneticists. Image source: Modified from T. S. Painter, J. Hered. 25, 465-476 (1934)
- 23. Genome of Drosophila In terms of base pairs, the fly genome is only around 5% of the size of the human genome -- that is, 132 million base pairs for the fly, compared with 3.2 billion base pairs for the human. In terms of the number of genes: The fly has approximately 15,500 genes on its four chromosomes, whereas humans have about 22,000 genes among their 23 chromosomes. Thus the density of genes per chromosome in Drosophila is higher than for the human genome.
- 24. Genome of Drosophila Humans and flies have retained the same genes from their common ancestor (known as homologs) over about 60% of their genome. Based on an initial comparison, approximately 60% of genes associated with human cancers and other genetic diseases are found in the fly genome.
- 25. The genome ofthe cenancestor Availability of complete genome sequences from the three domains of life creates an opportunity for the reconstruction of the complete genome of the common ancestor: Of minimal bacterial set (256 genes), 143 have orthologues in yeast (eukaryote) Universal translation apparatus suggests that cenancestor had a fully developed translation system Extreme differences in DNA replication apparatus Many fundamental metabolic processes are carried out by similar proteins in Archaea and eubacteria: Suggests a universal, autotrophic ancestor Not all central metabolism is universal (methanogenesis, photosynthesis etc.)
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