Comments on: Scientists “humanise” Foxp2 gene in mice to probe origins of human language

By: Doug Alder

Doug Alder — Sat, 30 May 2009 04:09:14 +0000

“What will we do tonight Brain”
“Same thing we do every night Pinky”
“What’s that Brain”
“TRY TO TAKE OVER THE WORLD!”
sorry couldn’t be helped

By: Sigmund

Sigmund — Fri, 29 May 2009 16:00:28 +0000

If changing one or two nucleotides of a 600 kb mouse gene to encode human specific amino acids is defined as ‘humanising’ then I guess I agree with you. My point (and its one that doesnt seem to be addressed in the paper) is that the gene itself is under multiple levels of regulation that may have important effects on the function of the gene. Testing the effects of changing the amino acids IS an important experiment but its only one step in a large process to define how the ‘gene’ (rather than the protein) functions differently in humans compared to mice. I certainly agree that the peer reviewers didn’t seem to think this point was important.
I work in genomic analysis, in particular looking at transcriptional and post transcriptional gene regulation. When I see a gene like this I automatically look for signs of regulation in these areas. For a paper like this its much more likely that it was sent for review, not to a scientist who specializes in gene regulation, but to scientists who specializes in FOXP2. I had a paper in review in Cell a little while back directly addressing post transcriptional regulation of a fairly well known gene. The comments from the reviewers showed that the editors had sent the paper to be reviewed only by researchers who worked on the protein of that gene and who had little or no experience of post transcriptional gene regulation (some of their comments were unbelievably ignorant on this matter).
The peer review process is certainly not perfect.
Still, I have no problem with the work overall, well done to the researchers involved. Its a nice study. I’d just prefer a little bit more circumspection in the discussion section regarding other changes that might affect the function of this gene.

By: Ed Yong

Ed Yong — Fri, 29 May 2009 15:12:32 +0000

Most of this is true, but as far as I'm concerned, describing the gene as "humanised" means that parts of it have been altered to match the human sequence, and not necessarily all of it. Judging by the title of the paper, the authors and the peer reviewers agree.

By: Sigmund

Sigmund — Fri, 29 May 2009 14:38:11 +0000

Ed, the human FOXP2 gene is over 600 kb in length with multiple differences between human and mouse.
The authors of this study changed two codons in exon 7 so it is entirely inappropriate to say the ‘gene’ was humanized.
The coding region of the gene was humanized.
The regulation of this gene in humans is very likely encoded in the parts of the gene outside the open reading frame (as evidenced by multiple human specific transcription factor binding sites, microRNA target sites, RNA binding protein sites and other regulatory and enhancing elements that are apparent in the human genomic sequence.
Its a nice study but overall very limited in terms of how much we can understand the function of this gene. In years to come the technical limitations of this sort of work will be oevercome and allow for the full gene sequence to be inserted.