Tuesday, September 25, 2007

How selfish DNA is put to work


Last year, in a paper published in PNAS in collaboration with Richard Cordaux (now at the University of Poitiers, France) and Mark Batzer (LSU), we reconstructed the evolutionary history of a primate fusion gene called SETMAR. I realize that's already an old story and it might sound like I am just self-promoting my own research on my own blog. But I thought it might serve as a good introduction to the kind of questions that I am interested in (and will post more about on this site in the future). It will also provide an example of how transposons and other forms of so-called 'junk DNA' can, on occasions, make themselves useful in the genome. Finally this is a story that generated quite a bit of web/blog discussion, some of them I have linked below.

What got me interested in this gene was the fact that half of it somehow derived from a transposase gene which used to be encoded by and serving selfishly a transposon called mariner. Thus it looks as if the transposase gene had been 'captured' and recycled to give birth to a new gene, and thus contribute to the advent of a new function.

There are two major questions that we wanted to address: first, when and how did the fusion happened? Second, what is the function of the new protein and what is the contribution of the transposon-derived part (ie. the transposase) to this function ? The paper provides a pretty clear answer to the first question and some bits of answers to the second question.

I'll give you a quick summary. First, you have to know that the transposase region of SETMAR is derived from a particular copy of a mariner family called Hsmar1. There are about 200 copies of these Hsmar1 elements in the human genome, and about 7,000 copies of a related but smaller and non-coding element called MADE1. We knew from another study that we published this year in Genome Research, that Hsmar1 and MADE1 were inserted around 45 Myr ago in the genome of an anthropoid primate ancestor. All the Hsmar1 elements are now inactivated by mutations which make them unable to encode a functional transposase enzyme, except for one copy: the one incorporated in SETMAR. The transposase region of SETMAR has retained an intact coding sequence, and we found that it is highly conserved and evolving under strong selective constraint in all anthropoid primates examined. However, it is precisely missing from the orthologous genomic region in prosimian primates (tarsier, lemurs) and in all other vertebrates that we looked at (see figure above). However, these species do have the SET portion of SETMAR. This data strongly suggest that SETMAR arose by insertion of a Hsmar1 copy downstream of a pre-exisiting SET gene sometime in the lineage of anthropoid primates, followed by transcriptional fusion to give rise to the present-day SETMAR. Amazingly enough, by comparing the SETMAR genomic sequence in diverse primates, we realized that the birth of the new gene was made possible by not just one, but a series of seemingly unlikely mutational events, including a transposon insertion and the creation of a new intron.

This intricate process of gene origination from a piece of so-called 'junk DNA' or, more accurately selfish DNA, attracted substantial media coverage, and gave rise to a number of interesting posts on several evo/discussion web sites, some of which are listed below (including an accurate and comprehensive rendition of the story in the lively Theology Web Campus):

Mechanisms in Evolution: the evolution of a new gene (Theology Web Campus)
Piecing Together a Gene: Nobel Intent (ARS Technica - Nobel Intent, followed by an animated discussion)
Brig Klyce's Cosmic Ancestry
Happy Birthday Primate Gene SETMAR (GMO Pundit aka David Tribe)

As to the present function of SETMAR in humans and other primates, you will find more in our paper and in two articles recently published (1, 2). And of course, I will keep you posted here or there.

12 comments:

Chris Harrison said...

Very interesting post Cedric.
Thanks for sharing, and I'm looking forward to more posts from you.

CedricF said...

Thanks Chris - I will try to post more in the next few days... There's so much that can be said about mobile elements and evolution.

I have to admit that even though I was thrilled to receive my first comments today, I am now feeling under pressure to post some more...! With my current hectic schedule, it makes me wonder if I'll be up to the challenge of keeping this blog alive. We'll see.

BTW - I've started reading your own blog. Very neat the moray eel jaws.

I'll comment about 'genes in conflict' in a minute.

Chris Harrison said...

Between "The Evolution of the Genome" and "Genes in Conflict", transposable elements have really caught my interest. I'm thrilled that I found a blog dedicated to TEs.

Even if you can't manage daily updates (not all of us are machines, except Brian), you'll still get readers and I'm sure your posts will be appreciated.

Thanks for the complements. I usually do blog more often than I have been recently. I blame it on the intrusion of real life.

John Logsdon said...

Glad to see you here, Cedric. Welcome to the world of blogging!

CedricF said...

Thanks John - It was so entertaining for me to read y'all lately that I am making an attempt to get involved more directly with this blog. I have doubts that I'll be able to post very regularly though. But I'll try my best to keep it alive!

Ali said...

You can find more information on DNA in:
http://www.geneticsofpregnancy.com/Encyclopedia/DNA.aspx?pid=2
This site contains information On Pregnancy Diseases And Genetic Testing.

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