Kinetochore reproduction theory may explain rapid chromosome evolution.

T decades ago, Todd (1) postulated that wholesale fission of all ‘‘mediocentric’’ (metacentric, submetacentric, and subtelocentric) chromosomes in a complement plays a major role in chromosome evolution. According to Todd, karyotypic fission produces, as a consequence of a single mutational ‘‘event,’’ dramatic differences in the diploid numbers of closely related species (2, 3). A diversity of karyotypes is generated through the random assortment of parent and fissioned homologous chromosomes. Immediate descendants of the fissioned parent would exhibit identical fundamental numbers of functional chromosomal arms but (potentially) very different diploid numbers. Todd saw karyotypic fission events, followed by the accumulation of pericentric inversions, as the driver for explosive speciation in adaptive radiations. He used the label ‘‘Karyotypic Fission Theory’’ to call attention to his implicit rejection of Darwinian gradualism in chromosomal evolution. Whole karyotypic fissioning can (at least theoretically) generate drastically different karyotypes in far fewer steps than are required according to competing explanations of chromosomal evolution, whether based on reciprocal or nonreciprocal chromosomal fission or fusion. Shortly after Todd’s article was published, it was dismissed as preposterous by one of the leading theorists of chromosomal evolution, M. J. D. White (4). If chromosomal fissioning occurs only under unusual circumstances, how could an entire karyotype be expected to fission? A serious problem was the lack of a plausible cellularymolecular mechanism. Indeed, even single chromosomal fissioning appeared difficult to explain (refs. 5 and 6; see ref. 7 for review). Some researchers saw fissioning as requiring a ready supply of extra centromeres, perhaps in the form of vestigial chromosomes (Fig. 1a). But the existence of spare vestigial chromosomes had never been demonstrated. Todd (1) proposed another mechanism— centromeric mis-division and subsequent repair (Fig. 1b). White (4) doubted ‘‘whether simple breakage through the centromere of a metacentric can produce two fully functional and stable telocentric chromosomes, capable of persisting indefinitely.’’ He added, ‘‘To suppose that all of the chromosomes of a karyotype would undergo this process simultaneously is equivalent to a belief in miracles, which has no place in science’’ (ref. 4, p. 401). With rare exceptions (8–11), Todd’s theory has been ignored for more than a quarter of a century. In an article published in a recent issue of PNAS, Robin Kolnicki (12) offers a plausible mechanism (Kinetochore Reproduction Theory) for simultaneous chromosomal fissioning. Her argument is largely theoretical, but cellularymolecular evidence is provided for each of its components. Many of the ideas presented are not new; dicentric chromosomes have been known since the 1930s (13), but their linkage to Todd’s Karyotypic Fission Theory is original with this paper. Kolnicki’s Kinetochore Reproduction Theory has several components. During DNA replication just before meiotic synapsis and sister chromatid segregation, a mutational agent stimulates the production of extra kinetochores on all (or most) of the mediocentric chromosomes’ newly synthesized sister strands. The newly synthesized strands now possess two functional kinetochores instead of one. These supernumerary kinetochores do not disrupt the distribution of chromosomes to daughter cells during meiosis because tension-sensitive mitotic checkpoints operate to prevent errors in chromosome segregation (as illustrated in Fig. 1 A of ref. 12). Assuming none of the supernumerary kinetochores is later inactivated, descendants will inherit di-