Forum:What Is Your Favorite Conserved Protein?

Question

[Mary]

I have an unusual question. I have been asked to write a piece for non-scientists that addresses some of the issues around the public acceptance of biotechnology and the usefulness of it now and in the future. One of the issues out there for the general public seems to be crossing species barriers.

Currently I am musing on including an example that shows an alignment of a handful of proteins to demonstrate how similar they can be across species. I think that might be a nice visual thing for people who haven't seen an alignment before to understand. And yet how the variations don't carry any "speciesness" per se. What I mean is that a zebrafish circadian clock gene put into yeast doesn't make the yeast a fish. (Yes, I know you get that, but out in the world there seems to be some confusion on this point).

I'm not sure this will end up being the direction I take -- I'm trying to connect to some good examples that people might grok without too much work on the reader's part. But I've toyed with a couple of other ideas as well and those might still be the direction I end up going.

I'm looking for some good examples. And I'm being deliberately vague on what I need to generate further discussion and ideas to see where that goes. And also because I'm not entirely firm that this is a good plan....

What I'd like to know from anyone are any suggestions on any one or more of these points:

• What is the most conserved protein you are familiar with? Could it be a good story? (A couple of the ones I've looked at already are pretty boring or would require more words than I can afford to explain what they are.)
• Do you know of a good story of a conserved protein story you've heard from other scientists?
• Have you seen one example work really well for non-scientists?
• Do you have other ideas of a way to get this across? Or bad ways to have done this?
• Would a more medical example be good? Or maybe something with beer yeast as a gentle and funny way to lead in to the conversation?

I don't need every detail, I'm willing to do the legwork on the backstory, but UniProt IDs and leads on some interesting papers would be handy as well.

Random additional thoughts are also welcomed.

Answer 1

[Michael]

The Argonaute protein is a good example. It is highly conserved (about 80% conserved residues, ~70% identical e.g. human and drosophila), found in (almost all) eukaryotes (plants and animals) and archea and even some bacteria, it is possibly a very old protein. It is not part of the core metabolism, but it is very handy for fuctional genomics, biotechnology, and has some medical application, because it is part of the RNA-interference pathway an can be used for gene-silencing by RNAi.

[Mary]

Ah, nice one. I have seen some really bizarre claims about silencing out there and that could be a way to tie that in as well. Thanks!

Answer 2

[Neilfws]

File this answer under "random additional thoughts." It probably does not count as a "good story" :) I'd go with your suggestions of medically-relevant or beer yeast-related for that.

I guess one approach to finding the "most conserved protein" is to consult a database where proteins are clustered into families, on the basis of sequence, structure or both and see which family has the most members.

Quick and dirty first pass using Pfam clans for this purpose:

1. Download Pfam-A.clans.tsv.gz

2. Try to read into R; discover that line 13813 is badly-formatted

   table(count.fields("Pfam-A.clans.tsv", sep = "\t", quote = ""))
   #     5     7 
   # 14830     1 
   
   which(count.fields("Pfam-A.clans.tsv", sep = "\t", quote = "") != 5)
   # [1] 13813
   

3. Fix that line in editor; now read into R and count the clan members:

   clans <- read.table("Pfam-A.clans-fixed.tsv", header = F, sep = "\t", stringsAsFactors = F, comment.char = "", quote = "")
   head(sort(table(clans$V2), decreasing = T))
   
   #   \\N CL0123 CL0023 CL0063 CL0236 CL0020 
   # 10268    202    198    180    123    117
   

So: clan with most members in Pfam-A is CL0123, helix-turn-helix.

You could also try looking at other resources (SCOP, KEGG enzymes...)

[Mary]

Yeah, I was thinking of something similar at a different resource--but love the idea of looking through a set like that for interesting stories. Thanks.

[Neilfws]

For maximum impact, I'd look for extremes: very high identity/similarity between very "different" species - e.g. E. coli and humans. One of the glycolytic enzymes, something like GAPDH?

By "very different" I mean "as commonly perceived." The ex-biochemist in me does not think people and bacteria are very different :)

[Mary]

Yeah, I was considering housekeeping ones too. Thinking "housekeeping" is also a concept people might connect with. One I considered was Calm1. Also a subliminal message to calm the eff down....

Answer 3

[Giovanni M Dall'Olio]

• The Histone proteins are among the most conserved in all organisms. These proteins carry a very important function, which is the packing of DNA, and therefore they can withstand very few mutations in their evolutionary history.
• The proteins of the glycolysis and the Krebbs cycle are also very well conserved. The former are conserved among all organisms, while the latter only in eukaryotic organisms.
• The proteins of N-glycosylation are also very well conserved among eukaryotes. Glycosylation is important for the correct folding of membrane proteins, so a defect in glycosylation leads to severe diseases.
• Some proteins of the Splicing apparatus are also very well conserved (ASF, BBP, U2AF)

If you are looking for inspiration for an article about proteins, check the "Protein of the month" page at Uniprot.

[Mary]

Good stuff, thanks for several ideas. And funny, just yesterday I was reading about the soybean nematode thing and considering that too!

Answer 4

[ugly.betty77]

Proteins involved in forming the ciliary/flagellar machinery of Chlamydomonas are highly conserved from chlamy (a green algae) all the way to human (vertebrate). They are also very relevant for "general public" for two reasons:

1. Defects in them can cause eye and kidney diseases. We are talking about links with real disease, not GWAS crap.
2. I presume you are only crossing species barriers and not national barrier. Your audience, the 'general public' of USA, does not believe in evolution, and cilia is given as an example for why evolution is false.

So, yes, cilia is a fascinating story, but make sure you are better story-teller than Mr. Behe.

Also check this out.

[Mary]

Heh--yeah, I'm less worried about the creationists, but of course they might be enlightened by this discussion.

Answer 5

[Bosco Ho]

If you're interested in the evolutionary history of proteins, I think the work of Joe Thornton's lab is particularly interesting.

Their lab builds phylogenetic trees of major hormone receptors, and then reconstructs their putative ancestors (long since extinct). Since the hormone receptors have specific affinities for different hormones that bind, this provides a beautiful assay to interpret the properties of the reconstructed putative ancestor.

[Mary]

Neat, thanks. Yes, this is the kind of direction that I was hoping others might offer to examples I wasn't familiar with.

Answer 6

[Bill Pearson]

The Pfam domain database may have some examples you find useful, because it lists some of the largest domain families (which are sometimes the largest protein families), and because it provides evolutionary detail about how the domains are distributed. For example, this link lists the 20 largest protein/domain/repeat families. Proteins at the top of the list have been seen hundreds of thousands of times (focus on families and domains, not repeats). Explanations of genomes often use an analogy to parts lists; the top 20 list gives a sense of some parts that are used in many hundreds of thousands of contexts. (And Pfam has pretty domain diagrams as well.)

[Mary]

Thanks--and for keeping in mind that pretty diagrams may be useful in this case too. I was also considering what to do for illustrations (with full credit, of course). And I wonder if "families" of proteins really is another good way to connect with non-sci folk on this too. Exactly what I was hoping from this thread--thanks everyone.

Answer 7

[Simon Cockell]

The one I remember from my Drosophila genetics days is Pax6. Expression of the mouse Pax6 gene in flies can drive the development of ectopic eyes.

This example nicely demonstrates conservation of function across distant species (true for many of the morphogenic proteins expressed during development) - and also shows the lack of 'mouseness' about the mouse gene - obviously the ectopic eyes are fly eyes.

See this paper by Halder and Callaerts and this paper by Chow et al (among plenty of others).

[Mary]

Heh. I thought about that one. But I'm not sure extra eyes coming out is the best point to make to calm people down about cross-species protein expression....

[Simon Cockell]

yes... I see your point :)

Answer 8

[Philipp Bayer]

I found this paper and had to think of this thread:

Cross-Amplification and Validation of SNPs Conserved over 44 Million Years between Seals and Dogs

Not exactly conserved proteins, but I think a good starting point to show how similar genomic regions between wildly different species can be.

Answer 9

[ugly.betty77]

I am surprised nobody mentioned the Hox genes, Hox clusters and Hox code. Hox family and the actins/dynein/myosin etc. (see my other comment) are among the most conserved set of proteins in animals, and you can make plenty of good stories, God willing :)

From the wikipedia article on Hox gene

The homeodomain protein motif is highly conserved across vast evolutionary distances. In addition, homeodomains of individual Hox proteins usually exhibit greater similarity to homeodomains in other species than to proteins encoded by adjacent genes within their own Hox cluster. These two observations led to the suggestions that Hox gene clusters evolved from a single Hox gene via tandem duplication and subsequent divergence and that a prototypic Hox gene cluster containing at least seven different Hox genes was present in the common ancestor of all bilaterian animals.[5]

The functional conservation of Hox proteins can be demonstrated by the fact that a fly can function perfectly well with a chicken Hox protein in place of its own.[6] This means that, despite having a last common ancestor that lived over 670 million years ago,[7] a given Hox protein in chickens and the homologous gene in flies are so similar that they can actually take each other's places.

Here's a good book on Hox.

Answer 10

[Anima Mundi]

ATP synthase is in my opinion a good subject: it is well conserved, its function is probably meaningful for non-specialists ("provides ready to go energy to the cell"), and there is a fervent discussion about its evolution.

Answer 11

[ugly.betty77]

Calmodulin is another highly conserved protein and plays important role in muscle action.

"Having changed only slightly over 1.5 billion years of evolution and being transcribed from three separate chromosomes in humans, expression levels of this protein shaped the beaks of Darwin’s finches."

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