No “fooling” around

No joke: today may be April Fool’s Day, but the BroadMinded Blog crew isn’t fooling around. We’ve gathered some of our favorite strange but true facts about chemical biology, population genetics, and the twists and turns of the genome. A special thanks to Alice McCarthy and Leah Eisenstadt for helping gather these.

Chemical space: The theoretical size of chemical space – the total number of all conceivable chemical compounds – has been estimated to range up to 10²⁰⁰ possible molecules. According to a paper published in Medicinal Research Reviews, this number drops to 10⁶⁰ for the number of small, organic compounds with active, drug-like properties. To put this vast number into context, that’s more than the atoms in a billion Earths. Click here to read one Broadie’s take on one of the great challenges facing those researchers that venture into chemical space.

A tiny fraction: Among the 3 billion letters of DNA in the human genome, only about 5% is thought to be functional. These genetic elements, interspersed throughout the genome, are found in other mammals, meaning that they are important enough to survival to have been retained through evolution. An even smaller part of the genome is thought to actually encode proteins: 1.5 percent. The other functional bits are thought to have other, yet unknown roles. Scientists have used a variety of methods to estimate the number of protein-coding genes in the genome. To arrive at the most recent count of human genes, a team of scientists led by Broad researchers scoured human DNA for places that not only looked like genes, but were also found in our primate cousins, chimpanzees and macaques (read more here).

Our folded genome: The DNA contained in our cells is intricately and tightly folded. If it weren’t, each cell’s genome would be around two meters long. Instead, DNA fits nicely into the nucleus, a compartment that is only about a hundredth of a millimeter in diameter – several times narrower than a human hair (for a sense of scale, check out this info graphic). In the fall of 2009, a research team led by scientists in the Boston area probed the three-dimensional structure of the genome – read more here.

Largest genome: As we reported last fall, scientists at The Royal Botanic Gardens, Kew, discovered that a small, white flower from Japan, Paris japonica, has the largest genome of any organism studied. P. japonica's genome contains a whopping 150 billion letters of DNA, making it 50 times the size of the human genome! But don't be misled – a huge genome doesn't necessarily mean an organism has an exceptional number of genes, and the number of genes in an organism's genome doesn't fully correlate with complexity: the mustard plant Arabidopsis thaliana has more genes (25,000) than are in the human genome, which contains roughly 21,000 genes. Scientists at the Broad conduct research to identify all parts of the genome to better understand how diversity among genomes yields the stunning array of organisms seen in nature.

Cheaper, faster sequencing: The per-base cost of DNA sequencing has fallen by about 100,000-fold over the past decade. The current generation of sequencing machines can read ~250 billion bases in a week, compared to ~25,000 in 1990 and ~5 million in 2000 (read more here). Scientists at the Broad Institute utilize next-generation sequencing to study variation in the human genome, diseases like diabetes and cancer, and the genomes of other organisms.

Ancient artifacts in the genome: In May 2010, we reported that the genome of Neandertals, the closest relatives to living humans who became extinct about 30,000 years ago, had been sequenced by scientists at the Max-Planck Institute together with colleagues at the Broad and elsewhere. The work revealed evidence that modern humans living at the time interbred with Neandertals, leaving behind an artifact in the human genome: present-day non-Africans inherited 1-4% of their genome from Neandertals.