Tuesday, December 23, 2008

Desktop archaeology uncovers human genome variability

Whenever I'm working on a project, my desk spontaneously grows piles of stuff, mostly books I'm reading, articles I should read, and journals I don't have time to read. When each project is finished, it's time to clean off the desk and get ready for the next one. Last Friday, I finished up four big projects (which you'll hear about later), and what followed was a serious desk cleaning. Cleaning the desk is always interesting, because you never know what you might find. It's like a little archaeological expedition. Who knows? The Ark of the Covenant could very well be lost somewhere on my desk.

On Friday, underneath the piles of stuff, I found an old issue of Nature (from May 1, 2008) with a post-it marking one of the pages. I flipped it open to see what caught my attention eight months ago, and I found the article Mapping and sequencing of structural variation from eight human genomes by Kidd et al. Oh yeah, I can see why I marked it. It's a fascinating paper.

They basically used a cloning and end-sequencing strategy to estimate structural variations in the human genome. Structural variations are things like large insertions, deletions, or inversions. We're talking more than a few kb but not as much as a whole chromosome arm. They looked at four Africans and four Asians and Europeans, for a comparison to the reference sequence. After finding a candidate rearrangement based on end sequences, they used restriction digests and some sequencing to validate the rearrangements. Read the paper for all the details.

Not surprisingly, they found a lot of interesting rearrangements, some of which were common to most of the eight sample sequences but not the reference sequence. Of the 6.1 million clones they mapped to the human genome with end sequences, 76,767 showed evidence of rearrangement. That's 1.26% of the clones, which is a lot. They found that rearrangements in 124 of 261 (47%) of the sequenced clones were caused by non-allelic homologous recombination between repeat sequences. Of those repeat sequences, segmental duplications were more common than L1 or alu repeats.

I think creationists can take two important lessons from this research. First, it adds evidence to my contention that there is no valid way to boil down the genomic similarity between humans and chimps. Looking at just genetic comparisons, the chimp/human similarity is >96% (often >99%) identity. But if "the human genome" is really a set of roughly equivalent but fairly variable genomes, then there is no way to boil down human/chimp genomic differences to a single number. Claiming that we have 98% the same DNA as a chimpanzee (which is very crudely correct) is a favorite propaganda tool of anticreationists and tends to get creationists' knickers in a knot. I think we all need to just chill out. There's a lot more to being human than just DNA (especially when we humans don't all have the same DNA).

The second lesson I take from this is that even in a relatively homogeneous species as humans, there are still genomic rearrangements that we can link to design. How? 1. We know that God created humans separately from chimpanzees. 2. We know that we share a vast majority of the same DNA sequences with chimps. 3. That shared DNA includes repetitive sequences and segmental duplications. 4. Repetitive sequences are ideal for nonallelic homologous recombination. Taken together, God must have designed us with repetitive sequences, which He knew would eventually be the sites of genomic rearrangements. These rearrangements, far from being degenerative corruptions of the "perfect" genome, were designed to happen. I admit that some of the rearrangements may have an adverse effect on human health, but in general, I would find it hard to believe that God created a genome so poorly designed as to fall apart because of a few (or even many) mutations. Or that God would create a genome designed to change only in detrimental ways. God's a better designer than that.