Chromosome 2 Fusion – Dead in a Day?

Ian Juby has stated explicitly that DDX11L2 is “critical for life” both here and here, where he refers to a paper written by Dr Jeffrey Tomkins in 2013.

But just how important is this DDX11L2 gene anyway? Well, we can get some clues just by looking at the name.

A rose by any other name?

Let’s break down the name of the gene itself – DDX – 11 – L – 2

DDX is short for “DEAD Box” – which is an RNA Helicase gene. Helicase genes are incredibly important, since these are the machines that unwind the DNA or RNA so that other molecular machines can read the underlying information.

There is an enormous family of DDX genes across our genome – DDX1, DDX2A, DDX2B, DDX3X, DDX3Y, DDX4, DDX5, DDX6, DDX10, DDX11, DDX17, DDX18, DDX19A, DDX19B, DDX20, DDX21, DDX23, DDX24, DDX25, DDX27, DDX28, DDX31, DDX39A, DDX39B, DDX41, DDX42, DDX43, DDX46, DDX47, DDX48, DDX49, DDX50, DDX51, DDX52, DDX53, DDX54, DDX55, DDX56, DDX58, DDX59 and DDX60.

Yup, that’s a grand total 41 DEAD Box Helicase protein-coding genes in the human genome.

DDX11 is just one of those 41 DEAD Box Helicase protein-coding genes. There’s nothing obviously special about DDX11 that makes it stand out from all the other DDX genes.

L stands for “Like”. Back in 2009, Valerio Costa reported on a transcripts family with 18 members whose nucleotide sequence bears a strong resemblance to DDX11. In other words, it looks “Like” DDX11, but it does not code for a protein – it’s a pseudogene. Note that all of these sequences are found in subtelomeric regions. Except for one. Can you guess which one?

2. Yup, DDX11L2 isn’t found near telomeres in the modern human genome, it’s all by itself in the middle of chromosome 2 – make of that what you will. To break things down even further, there are actually two transcripts for this pseudogene – NR_024004.1, which is the longer of the two transcripts, and straddles the putative fusion site – and NR_024005.2, the shorter transcript which does not cross the fusion site. Even if we hypothetically split chromosome 2 at the fusion point, the DDX11L2 pseudogene would still exist. All we would lose is this longer transcript.

So just to recap, what we are talking about here is a solitary alternately-spliced transcript from a pseudogene that is fairly similar to 17 other pseudogenes, and those pseudogenes as a whole bear some resemblance to an actual protein-coding gene – DDX11 – which is itself part of a larger family of 41 genes.

Now we have a rough idea of where this DDX11L2 pseudogene sits in the scheme of things, let’s talk hard numbers.

Droppin’ English. Express Yourself.

Gene expression data is often a good guide to the relative importance of a particular gene or transcript. If you had a bacterial infection, would you go to the doctor to get some antibiotics (with enough penicillin molecules to go around killing off all the bacteria) or would you go the homoeopathic option, where the solution has been diluted so many times that there is virtually no active ingredient left?

So, let’s look at how frequently DDX11L2 is expressed. If If you click on this link you’ll see that cells in the testes express DDX11L2 at a rate of 3.905 RPKM (Reads per Kilobase per Million mapped reads), in the pituitary gland at 0.936 RPKM, in the prostate at 0.893 RPKM and in the spleen at 0.882 RPKM.

If you then go up a step and look a the expression data for DDX11 itself, you’ll see that in the testes it is expressed at a rate of 8.477 RPKM, in the pituitary gland at 8.068 RPKM, in the prostate at 9.212 RPKM and in the spleen at 10.047 RPKM.

Already we can see that the DDX11 gene expression levels dwarf those of DDX11L2, but don’t forget we have 40 other DDX genes being transcribed as well! Let’s look at some other DDX genes:

                  DDX1    DDX3X    DDX5    DDX6    DDX11  DDX11L2
Testes           33.980  50.016  138.808   8.816   8.477    3.905
Pituitary Gland  35.394  34.213  321.470   7.100   8.068    0.936
Prostate         24.214  36.621  240.220   9.998   9.212    0.893
Spleen           23.889  50.052  347.019  10.811  10.047    0.882

Wow, DDX5 is expressed almost 400 times more often in the spleen that DDX11L2!

But remember how I said there were two transcripts? Well, the expression data above are from GTEx, and according to the locus given for DDX11L2, it only gives data for the shorter transcript – the one that does not overlap the fusion site.

If we look at AceView we can actually get a breakdown of how frequently the introns are sequenced in RNA-seq studies. The intron that corresponds to the fusion site was sequenced 682 times, while the intron common to both transcripts was sequenced a total of 3,186 times, implying that the longer transcripts make up only around 21.4% of the total DDX11L2 transcripts.

So, what are we to make of these numbers?

When Tomkins claims that DDX11L2 is a “highly expressed gene“, we have to ask “highly expressed relative to what exactly?” According to the AceView link above, this gene is expressed at “only 26.8% of the average gene“. If you then take into account the fact that the transcript that spans the fusion site makes up only 21.4% of transcripts for this gene, then it is expressed only 5.7% as frequently as an average gene.

If you were to hypothetically split this chromosome in half at the fusion site, you wouldn’t be “dead in a day” as Ian Juby likes to say, you would just lose a very lowly expressed transcript of a pseudogene. That pseudogene is part of a family of 17 other similar pseudogenes (DDX11L), which as a group, bear some resemblance to an actual protein-coding gene (DDX11). That protein-coding gene is then part of a much larger group of protein-coding genes (DDX).

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10 thoughts on “Chromosome 2 Fusion – Dead in a Day?

      1. I consider something evidence if it points positively toward one hypothesis to the exclusion of other hypotheses.

        Since the fusion is consistent with both evolution and creation, I don’t consider it evidence for either scenario.

        The fusion model is only a response to a creationist claim that humans and chimpanzees cannot share a common ancestor because they have a different number of chromosomes.

      2. I see what you mean, but I would say that successful risky predictions are indicators of a successful model, so when common descent predicts the fusion, I think it’s clear that the finding is favourable to evolution over creationism.
        In other words, the creation model can tolerate the fusion, but the common descent model is made stronger by it.

      3. I’ve been commenting about it over on Darwin’s God blog (Cornelius Hunter) and there was one line in his post that was pretty spot on:

        … such a fusion event would have occurred in, and spread through, an early human population. There is no evolutionary relationship revealed. Even if evolution is true, this fusion event would give us no evidence for it. The fused chromosome did not arise from another species, it was not inherited from a human-chimp common ancestor, or any other purported common ancestor.

        Put it in a syllogism:

        P1. If common descent is true, then two chromosomes must have fused together.
        P2. Two chromosomes fused together.
        C. Therefore common descent is true.

        It’s a formal logical fallacy called Affirming the Consequent.

      4. Again, I understand the point you’re making, but all I’m saying is that the fusion lends itself more to evolution than it does to creationism.

  1. i dont think so. id model also can predict this fusion. because we know that the ape genomes are very similar to human.

    1. How does ID predict the fusion just because of our similarity to apes? That would predict that humans have 48 chromosomes like the other apes.

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