Signature in the Synteny
In 1962, science fiction author Philip K. Dick published The Man in the High Castle, an “alternative history” novel set in a world where Roosevelt was assassinated in 1933 and where the Allies lost the second world war to the Axis. The novel gripped audiences because of the terrifyingly real “what if?” scenario where major changes in history were brought about by seemingly small events. The familiar backdrop of shared history between the novel and the real world drew readers into the narrative and made the changes that much more frightening.
In some ways, comparing the DNA sequence between related organisms is like reading alternative history novels. The hypothesis of common ancestry between similar organisms makes a very straightforward prediction about their genomes: it simply predicts that they were once the same genome, in the same ancestral species. This hypothesis also predicts that these two genomes, having gone their separate ways in the diverged species, will have accumulated changes once they separated. Like an alternative history, each genome has the same backstory, and then a history independent from the other after the point of separation.
What this implies for species related through common ancestry is that their genomes should be similar. For example, researchers have now sequenced the complete genomes of twelve sister species of Drosophila flies, including the fruit fly, Drosophila melanogaster. As you might expect, these species have similar genomes to one another. Species with the most similar genes are thought to have shared a common ancestor more recently; species with less similar genes are thought to have shared an ancestor less recently. These findings at the gene level also matched nicely with similarity of their physical characteristics.
Having the complete genome sequence of all twelve allowed researchers to compare synteny between them. “Synteny” is the scientific term for finding the same genes in the same order in two different species. (The higher the synteny, the more genes are in the same order).
Drosophila species have about 14,000 genes lined up “single file” along their chromosomes. Below is the representation of a tiny portion of a chromosome of Drosophila melanogaster. Each number corresponds to a different gene. Notice that genes, 2799, 2807, 2808, and 2828 (and others which are noted only by the ellipsis) make up a syntenic block, Similarly the genes on the right (along with others not shown) also make up a syntenic block.
Now, here are these genes in a sister species, Drosophila ananassae:
Compare the gene order of the two sister species. Can you figure out what has happened to disrupt the block of genes 2799, 2807, 2808, and 2828—genes which exist side by side in melanogaster?
Here’s a little hint:
Got it? There were two simultaneous breaks at some point in history so that 2799, 2807, 2808, and 2828 are no longer syntenic. Nor is the other block syntenic any more. Notice that in ananassae the same genes are present but they are in an inverted order. Two syntenic blocks have been broken up. We know exactly how it happened.
Now imagine analyzing this for all twelve species and—in each case—examining all 14,000 (or so) genes. The position of every chromosome break in the time since the 12 species had a common ancestor has been mapped out. 40 million years of history1 has been all laid out showing the set of disruptions of the single file order in which the genes are stored. We even know about how often those disruptions occur in a lineage: breaks, like the two described above, take place about once every 200,000 years. This rate has been fairly constant in the approximately 40 million year history of these twelve lineages. Species that diverged only recently (judged by an independent mechanism) have only a small number of breaks and a large amount of synteny, On the other hand, species which diverged longer ago (again, as judged by an independent mechanism), have a much larger number of breaks and a smaller degree of synteny.
From the theological point of view, most would have little concern with this data. We have been discussing fly species. This—in the mind of most, after all—is just divergence within the fly “kind.”
The story, however, doesn’t end there. At the same time that this was happening in flies, it was also happening in much larger organisms.
Like primates, for example.
18 million years ago, there were no humans, chimpanzees, gorillas, or gibbons on earth. Their last common ancestral species, however, was here.
Just like for flies, we can trace the changes in the single-file-order of the genes for this lineage as well. Let’s examine human chromosome #1 and compare it to the order of genes in the gibbon with whom we share that common ancestor of almost 20 million years ago.
The figure above shows human chromosome #1. The dark boxes within the chromosome are “geographical markers,” which need not concern us here. This chromosome has about 4,200 of our 21,000 (or so) genes. The gibbon has almost the same gene complement. Note, however, that there have been two inversions (the dotted lines, above) in that time. Also note that there has been some other shuffling. The genes at the left end of human chromosome #1 (about 250 or so) exist as a contiguous block in chromosome 5 in the gibbon. Similarly, if we consider the genes just a little further to the right, the next block of about 200 genes is found as a syntenic block on chromosome 9 in the gibbon…and so on. Clearly there has been some shuffling, but not a lot. Just like for Drosophila, the syntenic blocks are still largely in place.
The complete sequencing of the human and chimpanzee genomes has allowed scientists to do the same comparison with our most closely related living species. It is only about 6 million years since the common ancestor of humans and chimpanzees lived on earth. Since then, as with closely related species of Drosophila, there have been changes in synteny, but not a lot. There have been several large inversions that have been precisely mapped and many small inversions where only a few genes have been flipped. Not unexpectedly, there is even one case of shuffling between chromosomes: some genes that existed as two contiguous blocks in the common ancestor 6 million years ago, have become joined into one block in humans—the now-somewhat-famous chromosome #2.
This chromosome is made up of two blocks of genes joined together that are on totally separate chromosomes in chimpanzees and gorillas (see below). The fact that human chromosome #2 matches two ape chromosomes suggests that it resulted from a fusion between two smaller chromosomes like the ones we see as separate chromosomes in apes. This prediction was confirmed by DNA sequencing: we see all the chromosomal markers we would expect from a fusion event, and this evidence is now fairly well-known among followers of the creation/evolution discussion.
What makes shared synteny for humans and chimpanzees challenging from an anti-common descent viewpoint is that there is no good biological reason to find the same genes in the same order in unrelated organisms, and every good reason to expect very different gene orders. In fruit flies, for example, the more distantly-related species have quite different gene orders and chromosome structures, yet they all are healthy, robust species. In order words, many different gene orders can get the basic biology of being a fly done. Similarly, in mammals, many different gene arrangements can be found, sometimes even within species. In humans, many chromosome rearrangements are known that do not produce disease. Some anti-evolutionary groups claim that if human chromosome #2 was indeed the result of a fusion event, that this would have caused disease or fertility problems. This is not the case: tip-to-tip chromosome fusions do not necessarily cause defects or reduce fertility. For example, many different “races” of mice with different chromosomal arrangements are known, including examples with multiple tip-to-tip fusions like human chromosome #2. Many of these “races” of mice remain fully fertile when crossed with “normal” mice. Populations of mice with very different chromosome arrangements have also been shown to arise very rapidly in nature.
In summary, should God have wished to avoid the appearance of common ancestry between humans and chimpanzees, there seem to have been many gene orders and chromosome structures available to Him to use for either species. Indeed, we see more dissimilar orders and structures in many groups of species whose common ancestry is not controversial even for Young-Earth Creationists. Yet what we see in humans and chimpanzees are genomes that immediately give the impression of being slightly modified versions of the same genome. This pattern of genome organization similarity also fits with other independent lines of evidence (such as DNA sequence similarity and comparative anatomy) for arranging species into groups of relatedness (phylogenies) While this pattern makes perfect sense in light of common ancestry and acts as an important independent test of phylogenies, it continues to puzzle those who attempt to explain life apart from evolution.
In an upcoming post, we’ll explore how shared synteny allows researchers to predict where to find another feature of the human and chimpanzee genomes: shared pseudogenes.
1. The manner of dating the span of time over which Drosophila has been evolving is a fascinating story which the interested person can learn more about by examining the article and some of its references.
Bhutkar, A., Schaeffer, S.W., Russo, S.M., Xu, M., Smith, T.F., and Gelbart, W.M. (2008). Chromosomal rearrangement inferred from comparisons of 12 Drosophila genomes. Genetics 179; 1657-1680 Available here
Carbone L, Vessere GM, Hallers BFt, Zhu B, Osoegawa K, et al. (2006) A High-Resolution Map of Synteny Disruptions in Gibbon and Human Genomes. PLoS Genet 2(12): e223. Available here
Feuk, L., MacDonald, J.R., Tang, T., Carson, A.R., Li, M., Rao, G., Khaja, R. and Scherer, S.W. (2005). Discovery of human inversion polymorphisms by comparative analysis of human and chimpanzee DNA sequence assemblies. PLoS Genetics 1(4): e56. Available here
Kemkemer, Clause, Matthias Kohn, David N Cooper, Lutz Froenicke, Josef Högel, Horst Hameister and Hildegard Kehrer-Sawatzki. (2009). Gene synteny comparisons between different vertebrates provide new insights into breakage and fusion events during mammalian karyotype evolution. BMC Evolutionary Biology 2009, 9:84doi Available here