Abstract
DNA diversity in two segments of the Notch locus was surveyed in four populations of Drosophila melanogaster and two of D. simulans. In both species we observed evidence of non-steady-state evolution. In D. simulans we observed a significant excess of intermediate frequency variants in a non-African population. In D. melanogaster we observed a disparity between levels of sequence polymorphism and divergence between one of the Notch regions sequenced and other neutral X chromosome loci. The striking feature of the data is the high level of synonymous site divergence at Notch, which is the highest reported to date. To more thoroughly investigate the pattern of synonymous site evolution between these species, we developed a method for calibrating preferred, unpreferred, and equal synonymous substitutions by the effective (potential) number of such changes. In D. simulans, we find that preferred changes per "site" are evolving significantly faster than unpreferred changes at Notch. In contrast we observe a significantly faster per site substitution rate of unpreferred changes in D. melanogaster at this locus. These results suggest that positive selection, and not simply relaxation of constraint on codon bias, has contributed to the higher levels of unpreferred divergence along the D. melanogaster lineage at Notch.
Highlights
Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos
This is in contrast to synonymous site divergence between D. melanogaster and D. simulans, which is higher at Notch 3Ј than at Notch 5Ј (Table 1, Figure 3)
Our interest in the Notch locus stemmed from previous data suggesting that this region was unaffected by positive selection in D. melanogaster
Summary
Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. We sequenced two segments (Figure 1), which we call the 5Ј region (exons 3 and 4 and neighboring introns) and the 3Ј region (the 3Ј end of exon 6). EGF repeats are involved in the interaction of Notch with its ligands (i.e., Delta and Serrate) and the initiation of the Notch signaling pathway (Rebay et al 1991). The 3Ј region of exon 6 represents the beginning of the intracellular domain of Notch that mediates the ligand-dependent response of the Notch pathway within the cell (through interactions with a number of other proteins). The locations of the two regions sequenced (called Notch 5Ј and Notch 3Ј) are shown
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