Pharyngula

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Tuesday, November 29, 2005

We are as worms

Echoed on the Panda's Thumb

Genes in us multicellular eukaryotes are characterized by a peculiar feature: the DNA sequence is interrupted by stretches called introns that are transcribed into mRNA, but then cut out so that their sequence is not represented in the final protein product. The gene is spliced together out of portions called exons, excluding the introns, a bit of post-transcriptional editing that permits splice variants to be made, and that can increase the diversity of gene products. It's still a very strange and inefficient way to go about making proteins, though, and one that isn't necessary—bacteria, for instance, get along just fine without this intron nonsense.

intron history

Now here's a paper on the comparative analysis of introns with a pair of surprises. Surprise #1: the introns in our genes are highly conserved, and about two thirds of the human introns examined were also present in our urbilaterian ancestors at the very same amino acid position and phase. What that means is that this peculiar disruption of our genes occurred in multicellular animals before the Cambrian, and we have preserved this quirk for half a billion years. While sequences have diverged, the way the genes are organized in blocks has been conserved.

Surprise #2 (although it shouldn't be): we vertebrates are primitive. Other clades have modified their gene structure over evolutionary history more than we have, and our genes are more similar to those of some obscure marine worms than they are to those of insects, for instance, and have changed less than those of some of our closer relatives.

intron history

The paper examined the organization of many genes common to all bilaterians, across the phylogenetic spectrum illustrated to the right: some insects, C elegans, humans, the pufferfish Fugu, the ascidian Ciona, and as a representative of the relatively less well studied Lophotrochozoa, the marine worm Platynereis (Platynereis is an interesting animal for other reasons, retaining a primitively diverse collection of eyes).

Using the metric of introns, the Ecdysozoa are a sophisticated bunch. On average in the sample used, their genes contain on average 2.5-5.4 introns each, which sounds like a lot until you compare it to humans: we have 8.4 introns per gene. You might wonder whether evolution has added more introns to the human lineage, or pared introns out of the Ecdysozoan lineage…and the answer can be found by looking at that marine worm group. Platynereis has 7.8 introns per gene, suggesting that we share the primitive condition and that the Ecdysozoa have undergone more extensive evolutionary modification of their gene structure. Similarly, Ciona has experienced a rapid burst of evolutionary change and in this one parameter is more different from us than we are from an annelid! (Before anyone freaks out and claims that this invalidates the cladogram above, keep in mind that this is looking at only a subset of the genes that are clearly orthologous between humans and Platynereis (30 genes) and is based on one feature, the location of introns.)

The data below show how Platynereis is more similar in this parameter to vertebrates than to other protostomes.

intron history
(A) Fraction of Platynereis introns present in other Bilateria. The scheme on the left indicates the phylogenetic position of Platynereis (solid circle) as well as the other species and the investigated internal nodes (gray arrows). Note that the value for Deuterostomia comprises all introns found in Ciona, Fugu, and humans and thus indicates the minimal fraction of Platynereis introns present in Urbilateria. (B) Fraction of human introns present in other Bilateria. The value for Protostomia includes all introns found in Ecdysozoa and Platynereis, thereby giving a minimal estimate of human introns present in Urbilateria.

Another way to look at it is to see the Ecdysozoa as shedding introns at a relatively rapid pace in their evolution. The diagram below illustrates this as the percentage of ancestral introns lost at each branch of the tree—these animals have eliminated 60-80% of their introns.

intron history
Most parsimonious scenario of intron losses in different branches of the Protostomia as inferred from the data set. Numbers designate the percent of ancestral protostome introns lost along the respective branches. All data have their basis in the evaluation of 30 randomly chosen Platynereis genes with orthologs in other species.

The bottom line is that we're, we're…well, we're just slow. We've been held back a few grades at the evolution school. We've been taking the short bus down the road of history.

We conclude that, at the intron and exon level, Platynereis and humans can be regarded as similarly slow-evolving representatives of protostomes and deuterostomes, respectively.

Not that there's anything wrong with that, of course.

We can be proud of our unique character, but one thing we aren't is the most highly refined species on the planet. That honor is reserved for the small, deft creatures most ruthlessly honed by luck and natural selection.


Raible F, Tessmar-Raible K, Osoegawa K, Wincker P, Jubin C, Balavoine G, Ferrier D, Benes V, de Jong P, Weissenbach J, Bork P, Arendt D (2005) Vertebrate-type intron-rich genes in the marine annelid Platynereis dumerilii. Science. 310(5752):1325-6.


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Comments:
's avatar #51259: — 11/30  at  06:34 AM
"We are as worms" reminds me of Dune where Paul mates with a Giant Sandworm and they become one organism. Frank Herbert intuited that humans and worms are genetically compatible and their introns are exchangeable. Paul could never have fused with a Giant Squid. You can call me an intronist, but for me intron-challenged critters are primitive and inferior.

Quod natura non sunt turpia



#51261: — 11/30  at  07:10 AM
There may also be evolutionary pressure to retain introns in vertebrates, as they are one of the reasons for our complexity compared to invertebrates, i.e. why we only have ~5000 more genes than fruit flies and nematode worms.

Alternative splicing: The mouse genome contains ~25000 genes, but because of processes such as alternative splicing (different arrangements of exons), has been shown to produce 181,047 different transcripts. (http://www.sciencemag.org/cgi/content/abstract/309/5740/1559)

Noncoding RNAs: A large number (possibly the majority) of transcripts are now thought to be functional noncoding RNAs that are transcribed but are not translated into protein, and have a number of different functions. Many of these are found in the introns of protein coding genes. (http://www.sciencemag.org/cgi/content/abstract/309/5740/1529)



#51283: — 11/30  at  08:49 AM
Speaking of bacteria, there are (self-splicing) introns in some bacterial tRNA genes, and they also occur in protein-coding genes in some bacteriophages. Not to mention "protein introns" or inteins- yes, Virgina, there are self-splicing proteins as well as RNAs- which are found in bacerial protein-coding genes. (I realize PZ knows all about those things but many Pharyngula readers might not.)

The results discussed in this post seem to fit quite well the idea that introns originated as invasive parasitic elements (this is quite clear in the case of prokaryotic self-splicing introns, and inteins, which are all mobile elements) whose elimination by the host is slow and difficult. If there's really anything to the "benefit by increasing the diversity of gene products" argument, the resulting secondary benefit from that host adaptation would of course slow their elimination even more.



#51306: — 11/30  at  10:52 AM
from what I recall -
primitive - to avoid the prejorative connotation, think of it as verus "derived" - that is, pretty much the same as it was in the common ancestor. For example, the human hand is primitive, whereas the human foot is derived.
polypeptide vs. protein. - perhaps protein refers to the polypeptide chain after it has folded? maybe?

submit word - intron



#51324: Schwaumlaut — 11/30  at  12:11 PM
A polypeptide is the raw amino acid chain you get after tRNAs do their thing. These can be chopped up, folded, and combined with other molecules in a variety of ways to give finished proteins.

As for the use/non use of introns, introns probably serve some purpose in some organisms (evolutionary lemonade from lemons, as it were). Alternative splicing, if I'm not mistaken, occurs in coding regions (if an intron coded for something in some proteins, it wouldn't code nothing, no?). The real benefit that I can think of is that there's a lot more space for garbage like viruses/mistakes/etc. to happen without consequence. This comes with a cost, though: you're synthesizing a bunch of DNA that just sits there and looks weird.



#51329: Kagehi — 11/30  at  12:23 PM
The guy linked to by Jason seems to miss the point. *Past* versions of lizard morphology didn't have DNA to make reasonable guesses as to what went where. Think of it this way. Take a record player, 8-Track player, cassete player, CD-player and MP3 player, and having **no** concept how they work or what order they where created in, how would you group them? Probably like (with by natural extension the 'next' evolution):

Unknown
\---> Record player ---> CD Player ---> Holographic storage?
|
\---> Cassete ---> 8-Track ---> Reel-to-Reel data tapes?
|
\---> MP3 Player ---> PC?

Why? Because the morphology implies it. The reality is far more complicated, with a CD Player borrowing some features of the record player and the cassete, but ultimately having its digital storage method leading directly to the MP3 player. Without the "DNA", or in this case, a clear understanding of the technology used, its not possible from merely the morphological perspective to correctly organize them, especially if all still exist simultaneously. Though in the case of the 8-track, they might get it partly right, simply because you are more likely to still find the cassetes and reel-to-reel types than 8-tracks 'alive'. But one could find an 8-track that still works and incorrectly guess that it was a 'new' species, instead of one that is nearly comeplete extinct too.

This is hardly backpeddling or an attempt to resessitate invalid theory, any more than discovering that general relativity fails in some circumstances means everything back to before even newton must be thrown out and replaced with angels with giant bungie cords. Simply another example of a completely clueless twit talking about the supposed failings of something they have no understanding of. Go figure... lol

Any priest or shaman must be presumed guilty until proved innocent - Robert A. Heinlein



#51381: — 11/30  at  04:52 PM
A protein is made up of one or more peptide chains.

For example, as I recall, hemoglobin has four peptide chains plus a "heme" -- a big, flat structure that holds an iron ion in its centre. Mollusc blood has a copper ion, which is why it's blue. And funny thing about that: chlorophyll has a heme that holds a magnesium ion in its centre.



#51444: JVC — 12/01  at  05:05 AM
I've been reading Pharyngula for a year (via RSS), but this is the first post where I've been following the comments. That many readers don't appear to be professional biologists makes me curiously happy!

With that in mind, I hope that I don't offend anyone if I add/correct a few points...
Are introns bad? (#51243) Is there an obvious benefit for decreasing the number of introns other than improving splicing effeciency? (#51202)
A major reason "why introns are bad" is because their presence increases the cost of transcription. In mammals, for example, introns are ~4500 nucleotides long, while exons are only 150 nt. At about 9 exons per transcript (mRNA), each cell is therefore using its energy and resources to synthesise mRNA for which it needs less than 4% (the protein-coding exon parts). Obviously, that's quite a waste!
If [introns] were really detrimental, we would have gotten rid of them earlier in the evolutionary process. (#51246)
By "we", you mean humans, right? ;) Natural selection isn't always strong enough to drive evolution. Chance also plays an important role and this fact is often ignored by Creationists/ID-proponents. Darwinian (adaptive/positive) selection and evolution are not synonymous, the former is one component of the latter. I wish I didn't, but I get quite worked-up when Creationists refer to those who 'believe' in evolution as 'Darwinists'. Uh, not that I'm calling you a creationist, of course!
Introns are very important for domain swapping and splice variation. (#51203) There may also be evolutionary pressure to retain introns in vertebrates (#51261)
NOW they're important for the e.g. alternative splicing and non-coding RNAs, but that doesn't explain why humans still possess these 'primitive' introns found in worms. Due to, for instance, the transcriptional cost mention above, IMMEDIATE advantages are provided by getting rid of the introns. An organism doesn't think "Hmm, wouldn't it be nice if I kept this junk in my genome because, a few million years down the line, I could use them to create splice variants and regulatory non-coding RNAs". Sorry, this is evolutionary foresight and hovers dangerously close to a 'Just So' explanation.
prokaryotic self-splicing introns, and inteins, which are all mobile elements (#51283)
Inteins themselves are not mobile elements (they cannot spread across the genome or through a population), but their existence can harbor selfish genetic elements, most notably homing endonuclease genes, which have a beautifully simple mechanism for propogation.



#51450: — 12/01  at  08:02 AM
Thanks for the correction on inteins- I used to be a "real" biologist, and even worked in a lab that studied prokaryotic introns, but it's been some years now since I left the groves of academe. To add to point about the parasitic origin of Group III introns (the non-self-splicing ones that PZ was talking about), I gather there's pretty good support for the idea that they evolved from mobile, self-splicing Group II introns.



#51451: JVC — 12/01  at  08:21 AM
Yeah, there is, although I can't remember where I read it (too many years since I wrote a dissertation on that subject... brain hurts).
I used to be a "real" biologist
Me too, now I'm into molecular evolution! ;)



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