September 14, 2000
Letters to the Editor
To the Editors:
Michael Hagmann's story (1) on the sequence of Mycobacterium leprae propagates a serious misconception of how evolution works. The article is titled, “Leprosy's Dying Genome”. It reports the finding that M. leprae has has lost one third of its ancestral genome to deletion, and another third to mutational silencing, including genes involved in energy production and DNA replication. The article reports that a scientist in the sequencing study, Stewart Cole of Institute Pasteur, “thinks this massive gene loss has crippled the leprosy bacillus”, and he is quoted as saying, “I think it is on its way out.”
The first error in this viewpoint is that evolution has a destination in mind---that the genome is terminal and is “dying”, and thence, the bug itself. Genome death is certainly a Darwinian possibility, but only in species whose populations are so small that Muller's ratchet sets in, and ‘mutational meltdown' occurs (2). Nothing could be farther from the state of M. leprae populations, now infecting 750,000 new victims yearly. But the fallacy of imputing destinations to evolution is widely committed, as elucidated in (3). As a child I recall a friend telling me that someday, humans would no longer have the pinky finger; having shortened so much already, the small finger must obviously be ‘on its way out'.
The second error is to equate the loss of genes with “blight”, “wasteland”, and being “crippled”. The tenacity of M. leprae's hold on the human population contradicts there being anything crippled about it. Rather, the apparent ‘momentum' toward gene loss manifest in M. leprae is reminiscent of the evolutionary pattern seen in bacteria that have evolved to be obligate intracellular parasites. Widespread gene loss is due to the loss of stabilizing selection for their functions (4). A similar evolutionary progression is seen in neoplasms, where entire chromosome can be jettisoned on the way to malignancy (5); cancer may well be viewed as the evolutionary defection of host cells into the niche of intra-organismal parasite. The ‘dying genome' concept diverts us from the real question posed by the loss of genes in M. leprae: why the parasitic niche of M. leprae so much simpler than that of its cousin, M. tuberculosis?
Gene loss in M. leprae could conceivably be advantageous adaptations rather than defects. First, losing of 2/3 of its genes eliminates 2/3 of its potential antigens, and may help it modulate the host immune response so as to achieve chronicity. Second, the slow replication of M. leprae---which the article speculates is a consequence of its reduced genome---could in itself be an adaptation toward reduced virulence. Slow replication may spread M. leprae to more hosts by prolonging the time the host can transmit it. The evolutionary tuning of virulence is an established part of our understanding of pathogen evolution (6).
M. leprae is a tenacious survivor, and the above hypotheses would be more parsimonious than the novel phenomenon of a ‘dying genome'. Care must be taken when making analogies between dying and evolving; they are two fundamentally different biological phenomena.
Adjunct Assistant Professor
Information and Computer Sciences, University of Hawaii at Manoa.