Guy Walks Into a Bar and Thinks He's a Chimpanzee: The Unbearable Lightness of Chimp-Human Genome Similarity - Evolution News & Views

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Guy Walks Into a Bar and Thinks He's a Chimpanzee: The Unbearable Lightness of Chimp-Human Genome Similarity

I am often struck by how the topic of evolution in general, and chimp/human ancestry in particular, can be an immediate conversation opener that just as quickly becomes a conversation closer. Mind you, I don't go around buttonholing people at, say, my favorite lounge (this music will conjure up the atmosphere) about some phylogenetic arcana -- at least, I try not to do so. But for some strange reason, there exist individuals of good will who apparently feel called upon to "raise my consciousness" about some Darwinian facts that I've presumably gotten wrong. Not just a bit wrong, but astoundingly wrong. You see, to their way of thinking, I am in dire need of reeducation and they are there to charitably point the way to "help."

Here is an example of how "chats" like the one I'm talking about begin. After I have been formally introduced (though sometimes not) to an emissary of enlightenment, my just-made acquaintance proceeds to ask whether I've read a certain book (title withheld) that purportedly shows four things: We are 99% chimp; our chromosomes contain "scars" that are shared with those of our simian cousins; the DNA scars, like 98.5% of our genome, are simply junk; and these facts change everything we "know" about God. In response I invariably say, "How interesting," with a wan smile followed by, "Oh, sure, I've read parts of it." For me this is a taxing turn in the conversation for I must all at once feign attention, ask the bartender for another drink, and work to suppress my desire to bolt out the door. Sensing my unease, my new friend usually seems to read my restlessness as one of intellectual discomfort -- possibly fear. Anyhow, seeing me as the quarry, he leans in and expounds on each of the topics, his eyes glinting throughout with the impression that he is surrounding me via a four-pronged conceptual assault, a two-pincer strategy. (All the while, I am praising the heavenly host for the warm irreducible complexity of scotch.)

Then a lull in the barrage occurs. To his way of thinking, it is my guess, an opportunity is being provided for me to offer an unconditional surrender; or, at the very least, for me to acknowledge that pieces like the one just published in the Scientific American (Katherine S. Pollard, "What Makes Us Human? Comparisons of the genomes of humans and chimpanzees are revealing those rare stretches of DNA that are ours alone," April 20, 2009) are right when they assert that "our DNA blueprints are nearly 99 percent identical" to the sequences of chimps. Awaiting the white flag, my conversation partner will now sometimes try to emphasize that I have been at the receiving end of a coup de grâce,

By the way, this is the apogee or climax of the conversation. It is strictly downward from here on. But at such a critical juncture I proffer no surrender and, indeed, I mount a counter-offensive. Yes, yes, I know: The audacity...the rudeness. Whether my attempts to make my case are ever successful is unknown for my responses sooner or later elicit an abrupt termination of discourse. Regardless, my turn at the conversation goes something like this...

One can seriously call into question the statement that human and chimp genomes are 99% identical. For one thing, it has been noted in the literature that the exact degree of identity between the two genomes is as yet unknown (Cohen, J., 2007. "Relative differences: The myth of 1%," Science 316: 1836.). Part of the reason for this is if one decides to take into account the plethora of species-specific DNA insertions and deletions ("indels") that are present along any segment compared between chimp and human, the percentage of identity drops. Another reason is that duplications, inversions, translocations, and transpositions at all scales uniquely characterize the two genome sequences -- these have to be untangled before aligning the sequences in order to measure their similarity. Also, the 99% identity figure is often derived from protein-coding regions that only comprise about 1.5% of the two genomes. Many mammalian protein-coding regions are highly conserved, however. We also have to consider that a detailed comparison of certain "heterochromatic" chromosome regions between chimps and humans has yet to be made. In short, the figure of identity that one wants to use is dependent on various methodological factors.

As I continue in this vein, I notice that I am being given the universal gesture of "Wow, look at the time...it's really getting late...I'd love to pursue this matter further but I have better things to do..." by my interlocutor: He keeps staring at his watch and asking the bartender for the time. Since I'm now getting warmed up, I lean in and suggest to him that he should try his own chimp-human alignments and not take so-and-so's word for it -- after all, the sequences are publicly available. Why trust authority? (I can tell from his sandals and ponytail that this late 1960s reference will appeal to him.) But he has to make a parting shot and so, after commenting that only creationists are as recalcitrant to logic as I seem to be, he presents to me the ultimate criterion of truth, the standard by which I have failed. That criterion, the one I missed in school, comes through in a single sentence he utters: "Everything you just said, well, I have never heard this before." Taken aback and after I request that he repeat what I just heard, my now peeved acquaintance tells me (holding up his book) that since he has never read in his trusted sources that DNA sequence comparisons often require complicated alignments, that the data are filtered through software algorithms that in turn rest on a priori assumptions, etc., he must dismiss my first salvo.

He tallies the intellectual score as 4-0 in his favor.

At this break, three things happen. The bartender receives my nod that I want another drink and then, after he places it before me, I inquire as to whether he can play anything by Ethel Ennis -- I now want to listen to something languorous, music that will soothe the feeling of ennui that has come over me. Next, or simultaneously, my sparring partner makes one of two moves. Either he places his book into his hand-woven Inca-nesque bag and leaves without so much as a farewell, or he decides to tarry a bit longer and says, "You have no answer for ITSs, do you?"

ITSs...interstitial telomeric sequences...the chromosome scars, the pieces of junk DNA he was lecturing me about earlier. As you know, telomeres are the ends of chromosomes. In many species, including chimps and humans, the DNA sequences that are found at these genomic tips are tandem repetitions of TTAGGG. That's right...TTAGGGTTAGGGTTAGGG...over and over and over again. A notable exception to this rule is the fruit fly, an organism that in this regard has provided the junk DNA notion no succor, since its telomeres have complex combinations of three different retrotransposons instead of those six-basepair units. What is important to note, though, is that telomeric sequences are essential to the cell, and it seems that hardly a week does not pass without some new role being discovered for these elements.

How, precisely, are miles and miles of TTAGGG of significance? From the standpoint of chromosome architecture, the repetitive elements en masse have the propensity to form complicated topologies such as quadruplex DNA. These sequences or, rather, topographies are also bound by a host of chromatin proteins and particular RNAs to generate a unique "suborganelle" -- for the lack of better term -- at each end. As a matter of fact, the chromatin organization of telomeres can silence genes and has been linked to epigenetic modes of inheritance in yeast and fruit flies. Furthermore, different classes of transcripts emanate from telomeres and their flanking repetitive DNA regions, which are involved in various and sundry cellular and developmental operations.

I try to outline all the functions of telomeric repeats, but my friend tells me that I am getting off the subject.

He wants to me to focus on the ITSs, the tracks of the hexamer TTAGGG that reside within chromosome arms or around the centromere, not at the ends. I tell him that I was just coming to that topic. The story, you see, is that in the lineage leading up (or down, I forget which) to chimps and humans, a fusion of chromosome ends occurred -- two telomeres became stuck together, the DNA was stitched together, and now we find the remnants of this event on the inside of chromosomes. And to be fair, I concede at this point that the 2q13 ITS site shared by chimps and humans can be considered a synapomorphy, a five-dollar cladistic term meaning a genetic marker that the two species share. As this is said, it is apparent that the countenance of my acquaintance lightens a bit only to darken a second later. For I follow up by saying that of all the known ITSs, and there are many in the genomes of chimps and humans, as well as mice and rats and cows..., the 2q13 ITS is the only one that can be associated with an evolutionary breakpoint or fusion. The other ITSs, I hasten to add, do not square up with chromosomal breakpoints in primates (Farré M, Ponsà M, Bosch M. 2009. "Interstitial telomeric sequences (ITSs) are not located at the exact evolutionary breakpoints in primates," Cytogenetic and Genome Research 124(2): 128-131.). In brief, to hone in on the 2q13 ITS as being typical of what we see in the human and chimp genomes seems almost like cherry-picking data. Most are not DNA scars in the way they have been portrayed.

Exasperated with my stubbornness, the caffeine from innumerable herbal teas having only enhanced his tension, he rises from the bar and asks: "How, then, do you account for such ITSs in the first place...everyone knows they are out-of-place junk." I tell him that I do have an answer but that first I must be excused for a moment. While making my way back to the bar, I mentally rehearse so as to be as succinct as possible. My rejoinders are, simply, that ITSs reflect sites where TTAGGG repeats have been added to chromosomes by telomerases, that these repeats are moreover engineered -- literally synthesized by the telomerase machinery, that ITSs have a telomere-like chromatin organization and are associated with distinct sets of proteins, and that many have been linked to roles such a recombination hotspots. And just as I begin to reflect on where the references are in my bag that supports those points I notice...he is gone.


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