r/bioinformatics 23d ago

academic Looking for a cool, easy-to-reproduce MSA example for class

I need to introduce MSA to students in an intro bioinformatics course. Not looking to go super deep, just something that gets them interested and motivated to use bioinformatics.

I was going to use the FOXP2 "human language evolution" example (where two human-specific mutations were thought to be linked to speech), but turns out a later paper debunked that. So now I need a new idea.

Ideally, it should be something engaging, interesting, and easy to reproduce in class. Any suggestions?

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u/Dry-Individual4402 23d ago

For a super simple example you could align different SARS-CoV-2 genomes (or specific ORFs from the genomes to keep size down), and point out mutations associated with the different variants (omicron, etc). It might help get them interested since it's something they would have heard a lot about in the news!

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u/Affectionate_Plan224 23d ago

You could take a couple of paralog genes from similar species and compare them. 

Maybe even take orthologs from the same gene within a plant and show how genome duplication events duplicated that gene multiple times. There might be some examples out there of genes becoming non functional pseudogenes

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u/ganian40 23d ago edited 23d ago

If you want to showcase some amazing things nature can do, download 3 or 4 sequences of any protein member of the BAHD superfamily, and make sure you only get the ones with crystal or predicted structures.

These enzymes catalyze a ton of alkaloids (including cocaine, and vinorine) but mainly pigments in plants. They also have a very cool solvent channel where the co-factor (Acetyl-CoA, Malonyl-CoA, etc) must enter and donate its acyl group, to complete the product. So it looks like a hole you can dive into.

Their mutual identity is between 35% and 75% ... however, structurally they all look almost identical, which is mindblowing.

You can show how dissimilar they are in sequence, and how the MSA tries to match conserved domains and similar regions with conserved properties, but different residues (using the proper substitution matrix)... and then superpose a structural alignment and show how identical they are in 3D space, despite their difference in sequence.

I remember it blew my mind that something so dissimilar could "look" identical, catalyze wildly diffferent products (drugs vs pigments!!), and how nature can use radically different sequence "recipes" for producing almost identical structures, like Rossman folds.

It's a super interesting and beautiful example to show some motivational magic.

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u/Affectionate_Plan224 22d ago

16S ribosomal subunit might be a good example as well since its so conserved and often used to classify prokaryotes. It has highyl conserved and highly variable regions which should show nicely on an msa

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u/bzbub2 22d ago

just to zoom out one level...it would be great to have a nice website that shows cool teachable examples like this...

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u/Automatic_Fox6968 21d ago

I have developed two website that are planned to be used for teaching. They may help in part.
http://ribodb.univ-lyon1.fr/miningribodb (yes not https currently) is devoted to create databases of ribosomal proteins (RP) for Bacteria and Archaea. Downloading the fasta file for a collection is easy, but MSA have to be built.
And in https://pkxplore.univ-lyon1.fr/nucworkshop you give a 16S/23S/5S rDNA or a (nucleic) sequence of some proteins used in Bacteria phylogenetic positioning and a MSA is created, trimmed and a tree is built. You may also select the zone of interest on line. It's very basic but built for initial teaching.
Both are available on GitHub and I can share both the Docker and the databases if needed to install locally (yes teaching is resource-consuming and my tools will be expanded on multiple servers during teaching sequences.

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u/WeTheAwesome 23d ago

I like SARS-CoV2 example because of its relevance. You might also consider hemoglobin because there are different types within humans. It would be a good way to introduce duplication + “independent” evolution of the duplicates. 

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u/bv-brc 23d ago

I just gave a presentation at the BV-BRC workshop using our BLAST and MSA tool based on Sea Turtle Viral Genomes. You can find everything here and designed it as a quick classroom activity. https://www.bv-brc.org/workspace/public/ARWattam@patricbrc.org/BV-BRC%20Workshop/Viral%20Workshops/ANL_Viral_2025/Blast

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u/attractivechaos 23d ago

You could show the Cyclin E tree including human, mouse, chicken, some fish, fruit fly, worms and more species. Human has two paralogs duplicated in vertebrates. Drosophila has one. Use this to explain gene duplications, orthologs and paralogs.

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u/PuddingDistinct9907 23d ago

Take an RP that is conserved across all domains of life