Testing Genome Complexity

In their Report “The origins of genome complexity” (21 Nov., p. [1401][1]), M. Lynch and J. S. Conery argue that many modifications that determine eukaryotic genome complexity (such as retention of duplicate genes and transposable elements) emerged by random genetic drift (nonadaptively) in response to the long-term population-size reductions that accompanied increases in organism size. This is an important proposal because so-called “progressive evolution” (increase of complexity) is not explained by modern evolutionary theory. For example, bacteria are as adapted as mammals. The proposed solution is intriguing and paradoxical and may have profound philosophical implications: Progressive evolution is due to relaxation of selection [the general idea can be traced to S. Ohno's Evolution by Gene Duplication ([1][2])]. The authors express a hope that “[i]n the very near future, we will experience an enormous proliferation of phylogenetically well-distributed genomic data” (p. [1404][1]), which will allow testing of this model. They propose one general prediction that follows from this model: “carnivores should exhibit the genomic hallmarks of population-size reduction compared with related herbivores” (p. [1404][1]) (because population size decreases with the elevation of trophic level and with the increase of body size). However, this test is already available. The important genomic hallmark of population-size reduction, according to this model, is the enlargement of the genome caused by propagation of transposable elements and duplication of genomic segments. Therefore, carnivores and, generally, larger animals should have the larger genomes. However, comparison of genome sizes in four well-studied mammalian orders, differing in trophic level and body size (carnivores, artiodactyls, insectivores, and rodents) shows quite the opposite picture ([2][3]). Thus, rodents (low trophic level, small body size) have larger genomes than carnivores (high trophic level, moderate/large body size): 0.539 ± 0.007 versus 0.478 ± 0.025, respectively (Mann-Whitney, P < 10−3). Insectivores (high trophic level, small body size) also have larger genomes than carnivores: 0.553 ± 0.013 versus 0.478 ± 0.025, respectively ( P < 10−6). Artiodactyls (low trophic level, large body size) have smaller genomes than rodents: 0.508 ± 0.026 versus 0.539 ± 0.009, respectively ( P < 0.1). Thus, both the effect of trophic level and body size argue against Lynch and Conery's model. By reverse inference, this test supports the adaptive interpretation of genome enlargement. 1. 1. [↵][4] 1. S. Ohno , Evolution by Gene Duplication (Springer-Verlag, Heidelberg, Germany, 1970). 2. 2. [↵][5] The raw data are taken from the Animal Genome Size Database ([www.genomesize.com/][6]) and are presented in log-transformed picograms. # Response {#article-title-2} We thank Vinogradov for his comments on our Report, in which we called attention to the population-genetic mechanisms that may have been responsible for the dramatic genomic reorganization that occurred in the stem eukaryote and the subsequent modifications experienced in lineages of multicellular species. As a possible means to test the theory further, we somewhat cavalierly suggested comparisons of related carnivore and herbivore species, invoking ecological reasoning that suggests that the former should generally have reduced effective population sizes. Although Vinogradov argues that our theory is not supported in mammalian species, there are several concerns with his analysis. First, the Animal Genome Size Database (AGSD) contains multiple entries for several species and numerous genera are represented by more than one species. Moreover, given the close relationships of the members of individual lineages relative to the time scale of genomic evolutionary events, the data employed cannot be regarded as phylogenetically independent. Because the true lineage-specific means may be substantially different than the estimates presented, and the standard errors will certainly be much larger, no conclusions on the importance of selection can be derived from the data as presented. Second, a more thorough test would ideally consider issues such as intron number and size and mobile-element abundance, rather than focus on the less illuminating measure of total genome size. We certainly do not rule out adaptive evolution as a mechanism in genome evolution, and it is conceivable that the evolution of carnivory promotes the expansion of genome size through the proliferation of various gene families that facilitate this way of living. Third, the theory that we present is meant to explain broad patterns. Because evolution and population dynamics are stochastic processes, we expect to find significant scatter around the general expectations, and ample evidence of this can be found in our Report. Thus, the above caveats aside, work of this sort should be based on multiple independent contrasts between herbivores and carnivores, large- and small-body-sized species, and so forth. Finally, there is a real need to formally evaluate, with molecular marker data, whether carnivores do in fact have reduced effective population sizes. This is a potentially significant issue in mammals, where groups with different dietary habits can also have rather different mating systems and population dynamics. [1]: /lookup/doi/10.1126/science.1089370 [2]: #ref-1 [3]: #ref-2 [4]: #xref-ref-1-1 "View reference 1. in text" [5]: #xref-ref-2-1 "View reference 2. in text" [6]: http://www.genomesize. com/