Genome Complexity Conundrum and the Microbiome
One of the things that attracts me to the emerging domain of the microbiome is how little we know about the role of our microbial passengers on health and disease.
A point in fact: the Human Genome Project is widely considered one of the most significant modern accomplishments of humankind. The project, completed in 2003, mapped the entire library of human DNA—what we thought would be the biological blueprint for humanity.
In science, one discovery often begets other questions. The Human Microbiome Project was no different. Presumably, since humans are the penultimate species on the planet, one might assume we would have the most complex DNA on Earth. This assumption would be false. An interesting finding of the Human Genome Project was that humans only have between 20,000 and 25,000 genes (the exact number is a still a bit of a scientific debate), about half of a simple rice plant (Oryza sativa).
The disparity between the complexity of humans and the relative simplicity of our DNA is known as the Genome Complexity Conundrum. One explanation for the puzzle is the dependence of human biology on non-human DNA. Our mouths and guts contain the largest pool of non-human DNA. In 2001, Julian Davies, past president of the American Society for Microbiology, called attention to the conundrum in a letter to the Editor of Science. Davies wrote, “Until the synergistic activities between humans (and other animals) with their obligatory commensals have been elucidated, an understanding of human biology will remain incomplete.”
It turns out humans, and all other mammals are “superorganisms” consisting of human cells and microbial cells living in symbiosis. The term “metagenome" refers to the pooled DNA of humans and microbes. We have only studied the tip of the iceberg when it comes to how these complex interactions work.
In 2007, the United States National Institute of Health launched the Human Microbiome Project. The project was rolled out in two phases. Phase 1, the Human Microbiome Project 1, focused on identifying and characterizing human microbial flora. Phase 2, the Integrative Human Microbiome Project, focused on generating resources to characterize the microbiome and begin to elucidate the role of the microbiome in health and disease. Earlier this year, Nature published papers in the domains of diabetes, neonatology, and inflammatory bowel disease: the early fruits of the Integrative Human Microbiome Project.
The complexity of these systems is astounding. In August, Harvard scientists published an article that showed the number of microbial genes found in the human species might exceed the stars in the observable universe. At least half of the genes were unique to each human subject.
One thing is clear, unraveling the mysteries of the microbiome will fundamentally transform our understanding of health and disease.