It is Friday night, the kids are in bed and my wife is out with her friends. What do you do? Go to bed with a Sci-Fi book? No. Watch TV? No. Sort the laundry? NO!
The answer: I open a beer and read an article on duck genomes!
The article was published this week in Nature genetics, and I know at least two of the 51 authors (by the way, it is amazing how many authors there are on genome papers – more people than base pairs sometimes…). I have been waiting for this particular article a long time and have known that it is was on the way. In the pipeline, as they say.
Why so eager? Well, the duck – or more properly termed the Mallard, Anas platyrhynchos – is the main study organism in my lab. The most common duck in Europe, the most widespread duck in the world, the reservoir host of so many influenza A viruses, the most beautiful…. Eh, hmpf, perhaps not the most beautiful bird, but you get the picture – it is an important bird to me. And the duck genome is a treasure trove for us duck researchers; in essence the blueprints of what makes a duck a duck. Some of the base pairs in the genetic code might be coding for that particular trait you are interested, be it plumage, migration directions, or ability to withstand infection. And that’s when you need the blueprint.
The last couple of years, in the aftermath of highly pathogenic H5N1, you often hear the words Mallard and flu together. And it is right: Mallards are an important reservoir host for influenza A viruses. Meaning that they sustain perpetuation of virus subtypes in nature and are important for influenza A virus evolution. And, as you know by now, flu in humans and influenza A virus in birds are linked – thus flu concerns both ducks and men.
The paper of Huang and her 50 academic friends presents the overall genetic architecture of the Mallard genome and put it in relation to earlier bird genomes (chicken, turkey and zebra finch) and genomes from fish and mammals. It gives a tale on events that have occurred on really long time-scales, for instance the rate of gene duplication and gene loss over the last 100 million years. However, for me the most interesting is the second part of the article where they infect duck with highly-pathogenic H5N1 viruses and do what is called transcriptomics to investigate which genes that are affected by infection.
A transcriptome is a deep sequencing of mRNA transcripts, the transcribed genes on their way to the ribosomes to become proteins. By amplifying the RNA in your treated animals (in this case ducks infected with virus) and comparing the number of copies of particular gene mRNAs to untreated animals (in this case ducks not infected with virus) you can make a crude measurement of which genes that are up- or down-regulated upon infection. This can then help you to understand, and pinpoint particular genes with certain functions that may be important for immune processes and pathogenicity.
It is a great piece of work. And what I like is that it is the entry point for new studies; it’s like the opening of a highway where we other duck researchers can drive our cars. For my own part, I am extremely interested in the duck immune genes and the list of 150 cytokines, the Toll-like receptors, the defensins and the MHCs will be scrutinized in detail. We are already working on some of those, but now it becomes much easier to make progress.
Having said all these nice things, I do have some objections too. The strongest is how well the infection, and subsequent transcriptomes, reflect the natural situation. Experimental intranasal infections with a high titer of virus is not the natural way of infections, and hence may evoke biased responses, either because of wrong dosage, or because virus ends up in the wrong tissue. It is also important that controls and experimental animals measure the same thing, and in the right tissues. Some additional experiments, involving more animals and natural infections are warranted. But overall it is a great achievement and staggering amount of work poured down in this paper. Hats off for you – all 51 of you!
The rest of us, we roll up our sleeves and get to work with the blueprint of the duck! Interesting times ahead!
Full link to the article: http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.2657.html