Evaluating Disease Trends in Marine Ecosystems

For decades, scientists accepted that the nucleic acids, DNA and RNA, packed with thousands of protein-coding genes, were the sole purveyors of genetic information; all inherited traits, from eye color to shoe size, must be stored and expressed through nucleic acid mechanisms. But prions are an exception. These misshapen proteins are capable of growing, replicating, and infecting other cells—that is, they are heritable. And all without a scrap of DNA. Most famous as the culprit behind bovine spongiform encephalopathy, or mad cow disease, prions also occur naturally in some organisms and may play important roles in their growth and development. Prion-forming proteins normally exist as benign cellular components, such as enzymes or receptors. But they possess the innate ability to alter their three-dimensional structure, or fold, which changes their function and makes them almost impossible to destroy. Like other misfolded proteins, such as those responsible for Alzheimer's and Huntington's diseases, prions pack together and form aggregates. But what distinguishes prions from simple protein aggregates is their exponential growth and amplifi cation, which allows them to infect new host cells. Prions grow by inducing normal proteins to alter their shape and adhere to an initial aggregate " seed. " These growing masses are then thought to divide with the help of " chaperones,'' cellular proteins that aid in protein folding and transport, resulting in smaller prion particles called propagons. The propagons are then distributed to both mother and daughter cells during division, thereby infecting the next generation of cells. Though this theory of the prion life cycle was proposed a few years ago, scientists are still working out the underlying molecular mechanisms As they report in this issue, Lev Osherovich and colleagues dissected yeast prions and found that growth and heritability are controlled by two independent and " portable'' sequences. Furthermore, the heritability element seems to be the only thing that keeps slow growing protein aggregates from becoming infectious prions. Previous research showed that one end of the yeast protein, Sup35p, is critical for turning this normal housekeeping enzyme into a prion. The " prion-forming domain'' of Sup35p consists of two segments: one stretch rich in the amino acids glutamine and asparagine and another made up of several, small series of amino acids, called oligopeptides. Osherovich and colleagues had earlier found another yeast protein, New1p, which had similar segments, though in reverse order. To study the function of these sequences, the …