Pig-chimp genetics made easy

An elucidation of the issues

EUGENE M. MCCARTHY, PHD GENETICS

“Who will bell the cat? It’s easy to propose impossible remedies.”
Aesop’s Fables
Who will bell the cat

As I’ve pointed out elsewhere, the task of deciding whether certain portions of our genome are pig-derived is likely to be difficult even if such regions are actually there. Such, unfortunately, is the expectation under the hypothesis that the human race came into being via a process involving, first, a cross between pig and chimpanzee, then multiple generations of backcrossing to chimpanzee, and all of this happening many thousands of generations ago.

Why? Well, in the first place, it’s well known that backcross hybrids are hard to identify with molecular techniques (Vähä and Primmer 2006). And in the present case, not only the repeated generations of backcrossing to chimpanzees pose a problem, but also, because the crossing would have occurred anciently, the subsequent effects of recombination during thousands of generations of meiosis in the descendant hybrid population would make the genetic traces very difficult to detect today.

Dosage differences vs. sequence differences

Please keep in mind that I have explained elsewhere how there can be large differences in phenotype between two organisms even when there is zero difference with respect to their nucleotide sequences. At first this sounds impossible, but it is well established that major changes in phenotype can result from dosage differences rather than sequence differences. For example, someone with Down syndrome has an extra copy of chromosome 21 (a bigger dose of that chromosome, and of all the genes on it). And such individuals differ in many ways from those who don't have an extra copy. And yet, with respect to nucleotide sequences, those who do have an extra copy are identical to those who do not. Thus, even if every single one of the genes in our genome resembled chimpanzee more than pig, it could still be the case that hybridization has shifted the copy numbers of all of the various gene families in our genome away from chimpanzee and toward pig, with the result that we now have many pig-like phenotypes that chimps lack. But, again, it won't be easy to determine all those copy numbers in pig, human and chimpanzee, and to make comparisons between the three to see whether such shifts have actually occurred. That’s a huge task beyond the capabilities of any single human being.

Even though the gene dosages throughout the genome would be shifted toward pig, the sequence similarities would be shifted toward the backcross parent, that is, toward chimpanzee. (The reasons why dosages would shift one way even as sequence similarity shifted the other are given here.)

Nevertheless, some people claim it would be a cakewalk to detect the pig in our genome. Some of those who claim this are even professional geneticists. But I think they make this assertion only because they are unfamiliar with the genetics of hybridization.

In fact, it’s not easy for most people to understand the technical genetic issues relating to the question of whether humans might be pig-chimpanzee hybrids. But the muddling effects of the various events that occur in a hybridization process such as the one hypothesized can be explained by an analogy that most people will be able to understand.

The effect of combining two genomes. Imagine that you had two packs of 52 cards with each card bearing a unique number that sets it apart from all other cards in either pack. Call one pack the pig pack and the other the chimp pack. Now make a complete list of all the numbers in the pig pack and make a complete list of all the numbers in the chimp pack. Then shuffle the two packs together and spread the cards on the table. Under these circumstances, it would be fairly easy to show that some of the cards on the table were from the pig pack. All you’d have to do would be to pick up cards one at a time and compare the number on each with the numbers on the pig list. Once you found one such card, your search would be over.

The effect of a first backcross. Now imagine taking, at random, half the cards out of the ones you’ve spread on the table and replacing them with a new pack of chimp cards, so that only about 1/4 of the remaining cards spread on the table are pig cards. It now will be harder to find pig cards, but it can still be done with a reasonable amount of ease.

The effect of a second backcross. You take, at random, half the cards out of the ones you’ve spread on the table and replace them with a new pack of chimp cards so that only about 1/8 of the remaining cards spread on the table are pig cards. It now will be even harder to find pig cards, but it can still be done.

The effect of a third backcross. You take, at random, half the cards out of the ones you’ve spread on the table and replace them with a new pack of chimp cards so that only about 1/16 of the remaining cards spread on the table are pig cards. It now will be even more difficult to find pig cards, but it can still be done.

The effect of ignorance (The exact history of the process is unknown). Now suppose that you don’t know exactly how many times this repetitive process of backcrossing occurs, that is, how many times half the cards are taken out and replaced with a chimp pack, so that you don’t know exactly what fraction of the cards are likely to be from the original pig pack. The effect of this ignorance is that you cannot be sure exactly how thoroughly you will have to search before you can feel confident that no pig cards are on the table. Indeed, the only way you could be really sure would be to pick up every card.

The effect of recombination (gene conversion) during backcrossing. Now imagine that the cards were magical and that during each of the preceding steps some of the numbers on the pig cards changed to match numbers on the chimp cards so that the cards were really derived from the pig pack, but their numbers had been changed to chimp numbers.

The effect of recombination (gene conversion) during subsequent generations. Now imagine that the cards on the table go through a repeated process in which, during each round of the process, many pig cards get their numbers converted to chimp numbers and a few chimp cards get their numbers changed to pig numbers. That is, since the great majority of the DNA in a hybrid derived from multiple backcrosses to chimpanzee would be chimp-derived DNA, most conversions would be toward chimp.

The effect of thouands of generations of meiosis and gene conversion. Now imagine that this process of recombination and gene conversion is repeated many thousands of times.

The effect of thousands of generations of point mutation. Now imagine that throughout each of those thousands of repetitions, at any given stage, that for each of the cards, there is a small chance that a digit in the number on that card will change to some other digit.

The effect of representing ancient genomes with modern genomes. Now imagine that your list of pig numbers was based not on the actual pig pack that was put in at beginning of this process, but upon a pack that someone gave you who said he thought it was similar to the original pack, but that he didn’t really know exactly how similar it might be.

The effect of a large haystack. Now imagine that there were not 52 cards in each pack, but many millions. The human, pig and chimpanzee genomes all contain on the order of 3,000,000,000 nucleotides, and it is unknown which of those nucleotides should be compared in order to evaluate this hypothesis.

Not a cakewalk.

Indeed, comparative anatomy is a much easier and far more telling method of evaluating this question. I have already made the evidence from that source available.

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