How malleable is the eukaryotic genome? Extreme rate of chromosomal rearrangement in the genus Drosophila

Abstract

During the evolution of the genus Drosophila, the molecular organization of the major chromosomal elements has been repeatedly rearranged via the fixation of paracentric inversions. Little detailed information is available, however, on the extent and effect of these changes at the molecular level. In principle, a full description of the rate and pattern of change could reveal the limits, if any, to which the eukaryotic genome can accommodate reorganizations. We have constructed a high-density physical map of the largest chromosomal element in Drosophila repleta (chromosome 2) and compared the order and distances between the markers with those on the homologous chromosomal element (3R) in Drosophila melanogaster. The two species belong to different subgenera (Drosophila and Sophophora, respectively), which diverged 40-62 million years (Myr) ago and represent, thus, the farthest lineages within the Drosophila genus. The comparison reveals extensive reshuffling of gene order from centromere to telomere. Using a maximum likelihood method, we estimate that 114 +/- 14 paracentric inversions have been fixed in this chromosomal element since the divergence of the two species, that is, 0.9-1.4 inversions fixed per Myr. Comparison with available rates of chromosomal evolution, taking into account genome size, indicates that the Drosophila genome shows the highest rate found so far in any eukaryote. Twenty-one small segments (23-599 kb) comprising at least two independent (nonoverlapping) markers appear to be conserved between D. melanogaster and D. repleta. These results are consistent with the random breakage model and do not provide significant evidence of functional constraint of any kind. They support the notion that the Drosophila genome is extraordinarily malleable and has a modular organization. The high rate of chromosomal change also suggests a very limited transferability of the positional information from the Drosophila genome to other insects.

Figure 1

Large-scale comparison of the gene organization of Muller's element E between Drosophila melanogaster and Drosophila repleta. Connecting lines match the cytological position of orthologous markers. Dashed lines point out those markers whose location can be assigned to a single chromosomal site in D. melanogaster but that produce more than one hybridization signal in D. repleta. Mapped markers are indicated in blue (genes), green (cosmids), or red (P1 phages). When two or more markers provide redundant mapping information, only representative markers are shown. For precise mapping location of all the markers in D. melanogaster and D. repleta, see supplemental Table 1 (available on-line at http://www.genome.org). Red open rectangles indicate the 21 conserved segments comprising at least two independent (nonoverlapping) markers that presumably represent ancient physical associations not disrupted during the evolution of the two compared lineages. Their estimated sizes in D. melanogaster are indicated. Two genes localized by other authors, Hsrθ (Peters et al. 1984) and orb (H. Naveira, pers. comm.), are also included. Cosmid 200C9 does not appear as a single marker but as two sets of independent subclones (Ranz et al. 1999). Chromosomal arm 3R of D. melanogaster is partitioned into 20 (from 81–100) out of 102 numbered sections in which the D. melanogaster genome is subdivided (Bridges 1935). Chromosome 2 of D. repleta shows its seven main lettered sections according to Wharton (1942).

Figure 2

Randomization of chromosomal gene content after fixation of an increasing number of inversions. The conserved segments defined by at least two consecutive and independent markers (nonoverlapping) were considered as a single effective chromosomal site. This yielded a total of 87 positions for the analysis. Solid circles represent the mean values of Spearman's ρ from 1000 runs. Open circles represent the percentages of runs with a Spearman's ρ >0.3, that is, a correlation similar to that found between Drosophila melanogaster and Drosophila repleta.

Figure 3

Potential transferability of positional information from Drosophila melanogaster to taxa at different phylogenetic distances. The probability that a chromosomal stretch with a relative length l has not been disrupted after the fixation of 2n breakpoints is P = e^−2nl. 2n depends on the evolutionary divergence time between lineages compared. Divergence times indicated in the chart ×2 were taken from the comparisons among groups of species within the Sophophora subgenus (Throckmorton 1975), among subgenera within the Drosophila genus (Spicer 1988), and among some of the main insect orders (Friedrich and Tautz 1997), respectively. A rate of 1.85 disruptions per Myr was assumed in all cases.