Tuesday, March 9, 2010

The other human genome

For years, Joe Francis has argued that creationists really need to get on the ball with symbiosis studies. Theologically, mutualistic symbioses are very consistent with the nature of God. God values fellowship and community, and He Himself is a Trinity of persons. Mutualistic or commensal symbioses are extremely common, arguably more common than pathological interactions. The relative rarity of pathology over mutualism suggests a mechanism to account for some pathology: it's mutualism gone wrong. It also suggests that the normal condition is mutual cooperation not a struggle for existence.

As an example of the importance of symbiosis, consider the bacteria that live in your gut. Yes, in case you didn't know, bacteria live in your intestines. They help digest food, and studies even suggest that some bacteria may be essential for proper development. In other words, without those bacteria, you couldn't be you.

And that raises many weird questions, especially about the nature of the individual. What exactly is human? We know about human cells, and we know that human cells have mitochondria, whic look suspiciously like bacteria. Several years ago, we sequenced all the DNA in human cells, AKA the human genome. There's a lot about human cells that we don't understand, but we understand plenty more than we did 50 years ago. If it's true that we can't live (or we can't live well) without our bacterial ride-alongs, then what exactly are we? Are we "human" or are we a jumble of human and bacterial cells? For that matter, what are bacteria? Are they microscopic organisms? Are they external organelles?

So many questions...

Last week in Nature, Qin et al. reported a metagenomic analysis of the human gut microbes. They collected microbial DNA from the fecal samples of 124 individuals from Denmark and Spain (that must have been fun), and they sequenced a 576.7 Gb of raw DNA, which they processed to about 10.7 Gb of unique DNA. A typical bacterial genome might be around 3-4 Mb, so 10.7 Gb of DNA could represent the size of 3,000 bacterial genomes. Obviously, there are probably more in the set, since not all genomes would be completely sequenced.

From this DNA, Qin et al. found 14 million potential protein coding genes (or Open Reading Frames - ORFs). After weeding out redundant protein sequences, they found a set of 3.3 million ORFs. By comparison, the human genome contains about 20-25 thousand genes, which is less than 1% of the number of bacterial ORFs in Qin et al's sample.

Looking at it individually, each person of the 124 sampled had about half a million bacterial ORFs. Most of the 3.3 million ORFs (2.4 million, 70%) were present in only some individuals. Common ORFs found in more than half of the individuals numbered only 294,110, which is still more than ten times the number of genes in the human genome. According to Qin et al., individuals with irritable bowel disease "harboured, on average, 25% fewer genes than the individual not suffering from IBD."

In terms of the actual bacteria, they found 75 different bacterial species in at least half of the individuals and 18 in all individuals. Again, they found a difference between the bacterial species in healthy individuals and those from patients suffering from IBD.

So what do these bacterial ORFs do? By comparing the ORFs to proteins of known function, Qin et al. identified 6313 functions, nearly half of which are found in less than 10% of previously sequenced bacterial genomes. That makes sense, since bacteria with sequenced genomes come from a variety of environments, but the bacteria in this study come from the gut. The common functions probably represent important gut functions that are much less common in bacteria that live elsewhere.

Not surprisingly, Qin et al. identified specific functions related to digestion of sugars. Interestingly, they found the gut metagenome could degrade pectin and sorbitol, sugars that are found in fruits and vegetables and that humans cannot digest. The proteins produced by the gut metagenome can also synthesize compounds that are essential nutrients to humans, including some amino acids and certain vitamins like biotin.

I wish I had a clever way to wrap this up, but I'm just left amazed by the diversity and metabolic capability of the bacteria in the human gut. Future studies hope to sequence the genomes of 1000 human-associated bacteria. I'm sure my amazement will only grow as the complexity of the bacterial component of human life becomes better known.

Qin et al. 2010. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59-65.