Of Mice and Men: Unconserved Transcription Factors Binding


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You probably learned in high school biology class that the new DNA data has powerfully confirmed evolution. Take any gene and it reveals differences between the species exactly as we would expect. And this sentiment is not limited to high school textbooks. As the Chair of a university Biology department once wrote to me, “DNA sequences provide an absolute and irrefutable record” that evolution is a fact. “Virtually every single gene sequence we examine,” he explained, “can be seen to be represented in closely related species and in more distantly related species with increasing numbers of nucleotide changes as we look at more distant species.” It was, he concluded, “absolute proof, in hard copy, reiterated in every single gene of every single organism.” That is an unfortunately common misrepresentation of the data but the story doesn’t end there. The DNA evidence has falsified several other evolutionary predictions.

Vast stretches of identical DNA segments are found in distant species. Multitudes of differences are found in the DNA of cousin species. Retroviruses that were so often considered to be junk now must be viewed crucial to evolutionary history if Darwin was right. These are some obvious surprises that DNA offered up to evolutionists, but there are more subtle contradictions. One of them, which shows up repeatedly, is the way DNA interacts with proteins.

Consider a recent study of how transcription factor binding is not conserved between mice and men. Transcription factors are proteins that bind to DNA and influence which genes are expressed (transcribed). You may recall that proteins are created by first transcribing genes. So in this complex regulatory network, genes are transcribed to create transcription factor which then return to regulate gene expression.

Evolutionists believe their theory is crucial to biology. Nothing in biology makes sense, they say, except in the light of evolution. We know what questions to ask and where to look only because we have Darwin’s powerful ideas guiding and motivating our research. But transcription factors in the mouse and human do not follow the evolutionary pattern.

Not only do these transcription factors often bind to retrovirus sections of DNA—which evolutionists so often considered to be nothing more than worthless junk—they also usually do not bind in the same DNA locations in spite of their importance. As one commentary explained:

Remarkably, they find that the genomic locations of binding sites for two key regulatory proteins (OCT4 and NANOG) are poorly conserved across species, despite their functional importance in mammalian embryonic stem cell biology. […]

Unexpectedly, only ~5% of binding sites for the two transcription factors OCT4 and NANOG were found in orthologous positions in human and mouse ES cells, suggesting major differences in genome-wide binding profiles between species.

And the story becomes even more contradictory with many of the binding sites were found in non conserved junk DNA:

Remarkably, many of these RABS [repeat-associated binding sites] were found in lineage-specific repeat elements that are absent in the comparison species, suggesting that large numbers of binding sites arose more recently in evolution and may have rewired the regulatory architecture in embryonic stem cells on a substantial scale.

Furthermore, even those genes with conserved transcription factor binding often revealed more detailed differences in the particular binding location:

However, among genes whose OCT4 dependence was conserved between human and mouse, most of the OCT4 binding sites identified were not directly conserved. Instead, the disappearance of a binding site in one species was compensated for by the emergence of a new binding site for the same transcription factor nearby.

The commentary concludes that these findings are consistent with other recent lineage-specific findings:

The notion that some regulatory networks have substantially changed in evolution is also supported by recent independent observations of lineage-specific network rewiring in vertebrate preimplantation embryos and adult liver tissue.

Of course there have been no observations of "network rewiring," lineage-specific or otherwise. This is yet another unfortunate misrepresentation of science. Yes, the new findings are consistent with other recent findings that species differ in subtle yet dramatic ways. But none of this was expected by evolutionary theory. As the paper explains:

Together, these results suggest that many genes have been rewired into the core regulatory network of human embryonic stem cells following the insertion of transposable elements.

So species-specific studies are required:

In contrast, OCT4 and NANOG have very different binding profiles in human and mouse embryonic stem cells, with only ~5% of their sites being homologously occupied. The fact that there is also a limited concordance between regions experimentally observed to be bound and conserved elements, as determined from multispecies sequence alignments, implies that in vivo maps in the relevant species will be important in the study of many mammalian systems. Moreover, to help explain the vast occupancy differences, we showed that species-specific transposable elements have been an important source of new sites in both species.

In other words, evolution doesn’t help explain the findings. What is remarkable is how evolutionists are able to fit even contradictory evidence into their thinking:

we were also able to identify a group of human-specific target genes that show evidence of having been added to the core regulatory network of human embryonic stem cells via the insertion of transposable elements. Although we do not expect all binding events to directly influence gene expression, this data adds important support to a seminal hypothesis on the impact of repeats on the evolution of transcription regulation.

A seminal hypothesis? That is how evolutionists describe unfounded speculation that invokes serendipity to explain unexpected findings.

Genes added to the core regulatory network via the insertion of transposable elements? This is a remarkable example of how evolution has compromised both science and the peer review process. They conclude:

Our results reveal the striking plasticity of the core regulatory network of mammalian embryonic stem cells and the importance that transposable elements have had in facilitating this functional turnover.

This is what happens when evolution is mandated as true. Religion drives science and it matters.

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