1 / 13

PHYLOGENY

PHYLOGENY. Porcine insulin and human diabetes. Since 1982 people with insulin-dependent diabetes have been using recombinant human insulin. Prior to this time the most common insulin source was porcine (pig) insulin. Sheep and cows are killed for food in large numbers every day.

otis
Télécharger la présentation

PHYLOGENY

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. PHYLOGENY Porcine insulin and human diabetes

  2. Since 1982 people with insulin-dependent diabetes have been using recombinant human insulin. Prior to this time the most common insulin source was porcine (pig) insulin.

  3. Sheep and cows are killed for food in large numbers every day. Could ovine (sheep) insulin and bovine (cow) insulin have been used as an insulin source for diabetics instead of pigs?

  4. Using amino acid sequences for insulin in these animals and humans we can determine the evolutionary relationships (phylogeny) between these organisms. We can then decide whether or not porcine insulin was the right choice for humans.

  5. The next slide shows the amino acid sequences of a number of animals’ insulin. The alignment of these sequences shows the level of conservation between these molecules. An (*) indicates the amino acids that are found in all species. A (:) indicates some mutations that could affect the structure of the insulin molecule. A (.) indicates some mutations that do not have an effect on the structure of the insulin molecule. A ( ) indicates differences unique to each animal.

  6. The “INS_” prefix indicates an insulin molecule. The animals used are: INS_BOVINE Cow INS_SHEEP Sheep INS_PIG Pig INS_PANTR Chimpanzee INS_HUMAN Human INS_CHICK Chicken INS_HYDCO Pacific ratfish INS_ONCKE Salmon INS_MYXGL Atlantic hagfish

  7. Sequence alignment Consensus key * fully conserved residue : conservation of strong groups . conservation of weak groups no consensus (blank) INS_BOVIN MAL--WTRLRPLLALLALWPPPPARAFVNQHLCGSHLVEALYLVCGERGFFYTPKARREV INS_SHEEP MAL--WTRLVPLLALLALWAPAPAHAFVNQHLCGSHLVEALYLVCGERGFFYTPKARREV INS_PIG MAL--WTRLLPLLALLALWAPAPAQAFVNQHLCGSHLVEALYLVCGERGFFYTPKARREA INS_PANTR MAL--WMRLLPLLVLLALWGPDPASAFVNQHLCGSHLVEALYLVCGERGFFYTPKTRREA INS_HUMAN MAL--WMRLLPLLALLALWGPDPAAAFVNQHLCGSHLVEALYLVCGERGFFYTPKTRREA INS_CHICK MAL--WIRSLPLLALLVFSGPGTSYAAANQHLCGSHLVEALYLVCGERGFFYSPKARRDV INS_HYDCO --------------------------VPTQRLCGSHLVDALYFVCGERGFFYSPKPIREL INS_ONCKE MAF--WLQAASLLVLLALS-PG-VDAAAAQHLCGSHLVDALYLVCGEKGFFYTPK--RDV INS_MYXGL MALSPFLAAVIPLVLLLSRAPPSADTRTTGHLCGKDLVNALYIACGVRGFFYDPTKMKRD :***..**:***:.** :**** *. : INS_BOVIN EGPQVGALELAGGPG-----AGGL---EGPPQKRGIVEQCCASVCSLYQLENYCN INS_SHEEP EGPQVGALELAGGPG-----AGGL---EGPPQKRGIVEQCCAGVCSLYQLENYCN INS_PIG ENPQAGAVELGGGLGG--LQALAL---EGPPQKRGIVEQCCTSICSLYQLENYCN INS_PANTR EDLQVGQVELGGGPGAGSLQPLAL---EGSLQKRGIVEQCCTSICSLYQLENYCN INS_HUMAN EDLQVGQVELGGGPGAGSLQPLAL---EGSLQKRGIVEQCCTSICSLYQLENYCN INS_CHICK EQPLVSS-PLRGEAG--VLPFQQE---EYEKVKRGIVEQCCHNTCSLYQLENYCN INS_HYDCO EP-------LLG-----------------------IVEQCCHNTCSLANLEGYCN INS_ONCKE D-PLIGFLSPKSAKENEEYPFKDQ---TEMMVKRGIVEQCCHKPCNIFDLQNYCN INS_MYXGL TGALAAFLPLAYAEDNESQDDESIGINEVLKSKRGIVEQCCHKRCSIYDLENYCN ****** *.: :*:.***

  8. As an example of differences between species please note the coloured amino acids for sheep and cow (blue) and human, chimp and pig (red). Is there a limited conclusion that you can arrive at? On the following slide is a cladogram which is another method for viewing the relationships between these organisms. It is designed using the results of the sequence alignment.

  9. Chimpanzee Pacific ratfish Atlantic hagfish Salmon To page 10 To page 11

  10. Cladogram Use the cladogram to answer some questions: With respect to structure, which animal’s insulin is most closely related to human insulin? Is the insulin of sheep more closely related to human or chicken insulin? What is the evolutionary relationship between humans, pigs and chickens with respect to insulin? What is the relationship between human insulin and the insulin of pigs, sheep and cows? 10

  11. Cladogram If you were making the decision as to which animal to use as an insulin source for humans which animal would you choose? Are there any ethical issues associated with your choice? Using both the scientific and ethical information, which animal would be the most likely choice as an insulin donor? 11

  12. Structure of INSULIN Using the program Cn3D, you are able to visualise the 3-D structure of a large variety of proteins. Click on the button below to get you to the correct site. Then click on “View 3D Structure” and click “open”. If Cn3d is not on your computer then click on “Get Cn3D 4.1” link. There are many variations in the views possible. Try a few through: Style, Rendering Shortcuts and Colouring Shortcuts . You can grab the molecule and rotate it. Cn3D

  13. Can you see the two polypeptide chains? How many disulphide bonds have you found between the two chains? Try and imagine glucose molecules moving through the insulin between the two chains.

More Related