QnAs with Fred Gage.

Abstract

With the advent of rapid genome sequencing, the view of the human genome as a vast desert dotted with far-flung oases of functional genes has contended with a growing appreciation of the role of regulatory sequences in shaping gene expression. The fraction of the human genome’s noncoding component that can be considered functional remains to be established, but strewn across the seeming wasteland and interspersed with the protein-coding genes are hotbeds of activity, including mobile elements called retrotransposons. Molecular cousins of “jumping genes,” which plant biologist Barbara McClintock discovered in maize in the 1950s, retrotransposons can move through genomes, disrupting genes and displacing regulatory DNA. One group of retrotransposons, called long interspersed nuclear element-1 (LINE-1)—several of which are active in human somatic and sex cells—has become an intense focus of evolutionary research in recent years. Salk Institute neuroscientist Fred Gage has documented higher levels of LINE-1 mobility in certain cell types in nonhuman primates, such as chimpanzees and bonobos, compared with humans. His team has identified proteins that restrict the movement of LINE-1 in human cells, serving as putative guardians of genome integrity. Early hints suggest that the proteins in turn might be regulated through epigenetic mechanisms. Gage recently described his findings at the Arthur M. Sackler colloquium Epigenetic changes in the developing brain: Effects on behavior at the National Academy of Sciences in Washington, …