Evolutionary relationships and discovering new drugs
Technical & Teaching Notes
Introduction and context
This resource is designed to introduce post-16 students to phylogenetic trees, how they are constructed, and how they can be of importance for drug discovery. The students will also read four abstracts from scientific papers, with a view to extracting the key message from each.
A number of papers have been published about the search for Alzheimer’s treatments and anti-viral drugs in the genus Narcissus (daffodils). As there are so many different species in the genus, and because of the cost implications of research, some way of targeting which species to investigate is useful.
Due to evolution by natural selection closely related species are lively to have similar characteristics with some differences. This means that it is valuable to investigate species closely related to plants that we know contain useful chemicals, in the hope that they will contain similar but more effective chemicals. However, it is also valuable to investigate areas of the evolutionary tree that have not yet been investigated, in the hope that they may contain different chemicals which also have useful properties.
Students will compare sequence of amino acids in species of Narcissus, and use this to construct a phylogenetic tree showing the evolutionary relationships between them. They will then use this to decide which species should next be targeted for investigations by drug companies.
Some aspects of the topic of phylogenetic trees have been simplified for time purposes – for example, this includes only rooted trees, and only bifurcating trees.
This is a very broad subject and there is plenty of scope for teachers to develop their own resources on the topic. The raw data has been included with this resource, for those who wish to take it further. You might, for example, look at areas of change in the genome and areas of stability.
This resource includes both a teachers’ Powerpoint and student worksheets, together with the basic data Narcissus amino acid sequences. Those wishing to read the papers referred to in this resource should find them online.
We recommend teaching this subject in two parts, with the students creating their phylogenetic trees at home (either as a homework task or a challenge activity).
The first part (slides 1-16 in the Powerpoint, and pages 1-13 in the student worksheet) will last for approximately one lesson, and introduces phylogenetic trees, their importance, and how they are constructed.
After an initial introductory slide, students should work through the worksheet, beginning with the three abstracts from scientific papers. The material is new to students and will be challenging, so it is important that the teacher regularly checks that everyone on track, using the Powerpoint slides as a basis for explanations. Answers to the worksheet are given in the slides
Students then construct a phylogenetic tree of various members of the Narcissus family (pages 14 -15 in the student worksheet). This can be done either as a homework activity for the whole class, or set as a ‘challenge’ for students to tackle if they wish, with a prize for those who are successful. If set as a challenge, you can emphasise the fact that the correct tree could be one out of 13.7 billion different possibilities – compared to this, the chances of winning the lottery are one in 14 million!
Note that Sheet 5 is the completed phylogenetic tree, so this should not be given to students before the homework session.
In the next lesson, the teacher can review the trees produced by the students at home, and then walk through how the tree should be constructed. (This second part of the worksheet will not last an entire lesson.) The teacher should show how to identify the shared, derived character states, and highlight them in green (slide 18). The species should then be re-arranged within the table, so that species that share derived characteristics are next to each other (slide 19). Any two species that share all the same letters share a pair of branches on the tree. Some of these pairs of species will also share one or more derived characteristics with one other species, and can be linked as the next branch on the tree. Students continue until all species are linked together. The tree can be checked by ensuring that the sequence can be explained by only 14 changes, as shown in slide 21.
At this point, the teacher could also discuss evolution more generally, considering how the different species of Narcissus evolved. Students might consider, for example, what characteristics a fossil species might have had. The images of the different Narcissus flowers will give students an impression of the morphological variation between species.
Students should then be given sheet 5, the correct tree, and continue the rest of the worksheet (i.e. page 17 – Choosing species to investigate). Again, answers to the questions are given on the Powerpoint slides. Students should understand that closely related species should have similar characteristics, and so species related to a plant known to contain potentially beneficial drugs have a high chance of containing similar (or indeed, better) drugs. Similarly, if an area of the evolutionary tree that has not been investigated for useful drugs, this may well be worth considering. Students should be reminded that this is a means of making the search more efficient, not that this is a guaranteed method of drug discovery.
Note that the missing IC50 values given on page 17 are genuinely unknown at present: students are working with real unknown data.
Sequence data and opportunities for further development
These resources use a 162 Amino acid sequence of a fragment of the protein NADH dehydrogenase subunit F. Sequence data from Uniprot (www.uniprot.org) provided 41 records for species and subspecies of Narcissus (some species are duplicated) and 3 out-group species (Galanthus nivalis, Leucojum aestivum and Lapiedra martinezii).
To find the original data (freely available online) go to www.uniprot.org and do an advanced search to include the protein name, sequence length and genus (or out-group species name). The “basic data” word and excel documents include all these sequences identified with species name and year.
The basic Narcissus amino acid sequence data is available as part of this teaching package, in both Word and Excel format.
This resource was developed by Chris Graham of Long Road Sixth Form College, following a talk by Dr Jill Harrison of the Department of Plant Sciences, Cambridge University.
Development of the resource was funded by a SAPS Associate Award (www.saps.org.uk/awards).
Images of Narcissus from David Gough, Flickr user Dnnya, Ryan Somna and Carmona Rodriguez, all via Flickr Creative Commons.
Science & Plants for Schools: www.saps.org.uk
Evolutionary relationships and finding new drugs – teachers notes p.
This document may be photocopied for educational use in any institution taking part in the SAPS programme.
It may not be photocopied for any other purpose. Revised 2012.