Here's the abstract from the Wilson et al. (2008) paper. You be the judge.
Homologous sets of transcription factors direct conserved tissue-specific gene expression, yet transcription factor–binding events diverge rapidly between closely related species. We used hepatocytes from an aneuploid mouse strain carrying human chromosome 21 to determine, on a chromosomal scale, whether interspecies differences in transcriptional regulation are primarily directed by human genetic sequence or mouse nuclear environment. Virtually all transcription factor–binding locations, landmarks of transcription initiation, and the resulting gene expression observed in human hepatocytes were recapitulated across the entire human chromosome 21 in the mouse hepatocyte nucleus. Thus, in homologous tissues, genetic sequence is largely responsible for directing transcriptional programs; interspecies differences in epigenetic machinery, cellular environment, and transcription factors themselves play secondary roles.Grab some popcorn and a beer and sit back in your easy chair to watch how the evo-devo people talk themselves out of this one.
Wilson, M.D., Barbosa-Morais, N.L., Schmidt, D., Conboy, C.M., Vanes, L., Tybulewicz, V.L.J. Fisher, E.M.C., Tavaré, S., and Odom. D.T. (2008) Species-Specific Transcription in Mice Carrying Human Chromosome 21. Science 322: 434-438. [DOI: 10.1126/science.1160930]
Also provocative from the paper:
ReplyDeleteThe paper’s findings also call into question
one of the basic tenets of comparative
genomics: that evolutionary conservation can
serve as the primary tool for finding functional
sequences. Clearly, nonconserved
sequences are responsible for the
observed functional differences in binding
and expression of human and mouse genes in
the same cells.
In other words, the human-specific "junk" DNA is responsible for the humanness of the gene expression patterns. *wink*
"shrug"
ReplyDeleteIt's the same cell phenotype: hepatocyte. Try distinguishing a mouse hepatocyte from a human hepatocyte. It's not easy. Most homologous cell-tissue types are undistinguishable between mouse and human.
Of course, the very same sequence, if compared to another cell type (within the human or mouse), that is, that actually DOES have a noticeably different phenotype, does not express the same.
It's funny how they wash that datum form theri brains and then call "stupid" everyone who doesn't agree with their lame comparison of virtually identical cells... Do they even discuss phenotypic differences between mouse and human liver cells that are potentially relevant to C21? They way orthodoxy-hugging gomers think, I sincerely don't expect them to.
Don't expect virtually identical cell environments to produce great differences in the expression of the same sequence just because you are comparing them in different species. Expect them to produce virtually identical gene expression. As simple as that. I'm turning the TV off and going away; Larry will have to eat all that popcorn on his own.
ReplyDeleteTake care now! Bye bye then
By the way, Larry, the evo-devo crowd has minoritary superposition with the advances of epigenetics, which are made mostly by biochemists-molecular geneticists with little or no immediate evolutionary concerns.
ReplyDeleteJust so that you know.
While I don't know a fair bit about evo-devo, I don't see why this would make evo-devo people go nuts. Regulatory differences between species can be caused by numerous mechanisms, as the summary piece mentioned, and I'm sure there are cliques among the evo-devo crowd for each one. For instance, I'm sure Eric Davidson would be going nuts right now, but in a nice way.
ReplyDeleteI just realised that I said the same thing as the post above me.
ReplyDeleteMany researchers in epigenetics do see and discuss evolutionary implications, but I would not say that makes them evo-devo. Evolutionary, sure.
ReplyDeleteI'll admit - I don't get the reference to evo-devo either.
ReplyDeleteThe Fugu hematopoietic promoter,Lck, is 4.2 kb, significantly shorter than the mouse or human orthologue, which is why it's the preferred promoter for mouse models, despite a few amino acid differences. Fish have nucleated red blood cells, no bone marrow, and t-cells originate in the thymus. There are also differences in expression. Both fugu and mouse Lck shows up in mouse but not fish testes. We haven't figured out why yet.
ReplyDeleteI suspect the researchers haven't look hard enough at their hepatocytes is all.
Dear Mr Vargas,
ReplyDeletewhat might have escaped your attention is the following article published by Dr. Odom, prior to the Tc1 story:
Nat Genet. 2007 Jun;39(6):730-2. Epub 2007 May 21.
Tissue-specific transcriptional regulation has diverged significantly between human and mouse
In this paper Dr Odom clearly shows the divergence in transcription factor binding between human and mouse. The work you are refering to just shows that, when you then look at the human chromosome 21 in the mouse, it does not behave like the synomous mouse chromosome (regions) but like it does in its human environment.
It is sad that, given the strength of your language, you do not even have the decency to read the whole manuscript careful enough to follow the main argumentation of the paper.
Regards,
Tamir Chandra