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When PPLO Became Mycoplasma

The smallest cell has had a long career in the spotlight

Harold J. Morowitz

Not So Old

In the late 1960s Carl Woese was revolutionizing taxonomy based largely on the sequences of ribosomal RNA molecules. When he and Jack Maniloff looked at mycoplasma in this context, it became apparent that the organisms were descended from bacteria that had lost their cell walls and taken up a parasitic existence. The lush environments to which they became adapted—such as the humid greenhouse environs of the human lung—allowed them to shed swaths of their genome and metabolic capacity, living instead as obligate parasites dependent on biomolecules synthesized by their hosts.

From serendipity to implacable reductionism: Our original reason for studying PPLOs, to learn what there was to be learned about the original cells at the origin of life, had been completely misdirected. Rather than being an early taxon, it was a late one—very late. Among the newest of the microbes. It had lost size and genome due to its life in hosts of the Cambrian or later. While I try to think of a moral for this story, I’ll say in an aside: Sorry, Dr. Calvin. Mea culpa. In another bit of serendipity, Carl Woese, a coauthor of one of our earliest PPLO papers, developed the technique and scientific framework that solved some of our early confusion about who the mycoplasma really were. This nucleotide-sequence work was long after I had left the mycoplasma genome and turned attention to the mycoplasma membrane, another source of fascination offered up by this organism.

In 1980 Mycoplasma genitalium was isolated from a case of non-gonococcal urethritis. By then I had left this field of research. Sometime thereafter, Clyde Hutchison of the University of North Carolina began stalking the smallest genome, including sequencing its DNA. In 1995 a group at the Institute of Genomic Research headed by Claire M. Fraser finished the complete sequence of the Mycoplasma genitalium genome. Among the coauthors of the published report were Clyde Hutchison, Hamilton Smith, and Craig Venter. Mycoplasma has moved in my mind from one of the oldest to one of the most recent microbes. Indeed, in the hands of Venter and his crew it is moving into the future. If they are fully successful and start seeking a name for their entities, perhaps they might call them PPLOs—patent-pending laboratory organisms..

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