Evolutionary History of a Gene Controlling Brain Size

When James Watson and Francis Crick reported the structure of DNA in 1953, the mechanism of inheritance was instantly apparent. The complementary pairing of the DNA bases in the double helix, the pair famously wrote, “immediately suggests a possible copying mechanism for the genetic material.’’ The structure helped explain one of the central problems of modern biology: how does genetic material get faithfully replicated and then passed on from generation to generation? It was long thought that DNA is the only unit of inheritance. Since then, it’s become clear that molecules of DNA are packaged into highly organized superstructures that themselves are inherited. These structures play a signifi cant role in the regulation of genes by preventing or facilitating protein–DNA interactions. In the eukaryotic cell (a cell with a nucleus), DNA exists as long threadlike molecules—a typical human cell contains some 6.5 feet (2 meters) of DNA—that associate with a variety of proteins to form a network called chromatin. Genomic DNA wraps around specialized DNApacking proteins called histones to form nucleosomes, which condense chromatin into chromosomes and thereby infl uence chromosome behavior. Chromosomes are in turn packaged in increasingly higher levels of organization, with some parts being dispersed and others condensed. The most condensed region is called heterochromatin, or silent chromatin. Gene expression is largely silent in these regions, since the proteins required for transcription can’t access DNA to transcribe genes when chromosomes are so tightly packed. Other regions of chromosomes exist in an extended state, called euchromatin. This is the most genetically active state; with genes exposed, transcription can easily occur. As chromatin shifts between these states, it infl uences gene expression, largely through the interactions of histones and large protein complexes that together assemble, remodel, and modify chromatin. Since proper cell function depends largely on activating the right gene at the right time, mechanisms have evolved that protect active genes from the intrusions of silencing structures like heterochromatin.