ABSTRACT

The operation of the adult mammalian brain involves a large fraction of the genome.1,2 Upward of 50% of the gene complement is expressed in even single discrete brain regions such as the cerebellum, striatum, and hippocampus. Transcriptional complexity in the brain is unusually high compared with other organs, and roughly 40% of all genes are transcribed in two or more alternative forms.3 Development adds another major axis of complexity. In small mammals such as mice, assembling a brain is a beautifully choreographed dance that involves the proliferation, migration, differentiation, and interconnection of 75 million neurons, 25 million glial cells, and a web of 10 million or more blood vessel cells over a 30-day period. In humans, this process involves three orders of magnitude more neurons and their supporting cast and takes a decade or two.4 It seems conservative to estimate that 75% or more of the mammalian genome is engaged at some stage of making or maintaining the brain.