We’ve been discussing the recent groundbreaking Nature paper which reported “complete” sequences of ape genomes, and the fact that they show a 14 percent to 14.9 percent total genetic difference between humans and chimpanzees. As we explained, this is the result of summing ~12.5 percent to 13.3 percent difference from the “gap divergence,” essentially representing non-alignable sections of the genomes, plus about 1.5 percent to 1.6 percent difference in the alignable sections in the genomes. 

The Authors’ Interpretation

I contacted the corresponding authors of the original study and they very kindly offered their interpretation of the differences between the human and chimp genomes. In their view, ~12.5 percent to 14 percent differences stemming from the non-alignable sections reflect the fact that certain portions of the genomes are “highly mutable.” They emphasize that “most” of the human and chimp genomes are still only ~1 percent different, and they believe this indicates a close relationship between the two species.

That’s fine and it is one possible interpretation. Yet it has some problems.

For one, saying that “most” of the two genomes have only a ~1 percent different ignores the huge differences in the rest of the genomes. It’s kind of like saying “the parts that are most similar are the parts that are most similar” (my paraphrase) — a truism that is not very helpful. What about the huge genome sections that aren’t alignable — don’t they matter? 

For two, this interpretation seems to evoke the old dubious tactic of dismissing the so-called “highly mutable” DNA as unimportant junk that has accumulated due to random mutations, and therefore can be ignored because it is (allegedly) not relevant to encoding meaningful differences between species. But there are multiple reasons why it doesn’t seem like the DNA differences between humans and chimps represent junk. 

Encoding Our Big Brains

As a first example, the explainer article in Nature notes that some of the newly revealed DNA differences in the human genome are vital for encoding our big brains that distinguish our species: 

For example, human-specific copy-number increases of some genes are thought to be involved in regulating the expansion in the volume of our frontal cortex, the brain region responsible for higher cognitive functions. 

But the technical paper notes that much of the newly sequenced DNA included in these “complete” ape genomes is “repetitive” DNA, and it seems that different copy numbers of this “repetitive DNA” is responsible for much of the “gap divergence” between these genomes. Does that mean we’re just looking at junk DNA? Again, the answer is no. 

Repetitive DNA is Highly Functional

Another recent study in Nucleic Acids Research — which is precisely about these newly sequenced ape genomes, and is authored by some of the same researchers who sequenced these complete ape genomes — suggests that precisely this newly sequenced repetitive DNA can perform important functions as “non-B” DNA. According to that paper, non-B DNA is known to be “important regulators of cellular processes” and has “unequivocal importance for genome function.” The paper elaborates:

Non-canonical (non-B) DNA structures — e.g. bent DNA, hairpins, G-quadruplexes (G4s), Z-DNA, etc.—which form at certain sequence motifs (e.g. A-phased repeats, inverted repeats, etc.), have emerged as important regulators of cellular processes and drivers of genome evolution.

[…]

Non-B DNA is increasingly recognized as a major regulator of myriad processes in the mammalian cell. Non-B DNA structures are involved in replication initiation. G4s affect the life cycle of L1 transposable elements and protect chromosome ends at telomeres. Non-B DNA has been implicated in regulating transcription. G4s regulate chromatin organization and methylation of CpG islands. The transcribed non-B DNA motifs can form structured RNA, which regulates alternative splicing, translation of messenger RNA, and function of non-coding RNA.

Non-B DNA has also been implicated in the definition and function of centromeres. For example, inverted repeats forming non-B DNA have been hypothesized to define centromeres, which would resolve the CENP-B paradox. Indeed, non-B DNA might play a role attributed to CENP-B, the highly conserved protein binding motif present at centromeres across a range of taxa and proposed to be involved in centromere formation—but paradoxically missing entirely on some chromosomes. Recent studies also found enrichment at centromeres for G4s in Drosophila and Z-DNA, and A-phased, direct, and mirror repeats in plants and argued that non-B DNA is important for centromere activity and stability. [Internal citations removed.]

If all that’s a bit too technical for you, a press release about this Nucleic Acids Research paper details just what this repetitive non-B DNA can do: 

Non-B DNA can take many forms, including bent DNA, hairpins, G-quadruplexes (G4s), and Z-DNA based on certain sequence motifs, which tend to be repetitive. These structures have recently been implicated in several cellular processes, such as DNA replication initiation during cell division, gene expression regulation, and the function of telomeres — the caps at the ends of chromosomes — and centromeres, chromosomal structures that play a crucial role during cell division.

In other words, the repetitive DNA which makes up large portions of the newly discovered genetic differences between humans and chimps very likely has functional importance and can’t be dismissed as unimportant junk DNA residing in so-called “highly mutable” regions. 

This Doesn’t Affect My Main Point

But the reality is that none of these points above affect my main point here, which is the following: For years the public has been told countless times that the human and chimp genomes are only 1 percent different — and these completely sequenced ape genomes show that statistic is wrong by an order of magnitude. There are huge portions of the human and chimp genomes that are so different that they simply cannot be aligned and compared. The “1 percent” human-chimp genetic difference was an icon of evolution, in biologist Jonathan Wells’s term, and that icon has fallen. 

As I mentioned in my first article, icons of evolution are like “zombies” (also Dr. Wells’s term) and they don’t die easily. So expect to continue to see the 1 percent statistic cited. Sometimes this will simply be repetition done in ignorance by those who aren’t up on the science. Other times, scientists may make reference to the sections of human and chimp genomes that are “most” similar. But that is not the whole story. After the publication of this Nature paper, I don’t think it’s fair or meaningful to simply say that “most” of the human genome is only ~1 percent different without also acknowledging that 12.5 percent to 14 percent of the genomes are so different that they can’t even be aligned to make a comparison. The “1 percent” statistic is far from the whole story. Indeed, citing it without the further context I’ve discussed here is a blatant misrepresentation. This reality needs to be acknowledged — always.