Limits...
The life cycle of Drosophila orphan genes.

Palmieri N, Kosiol C, Schlötterer C - Elife (2014)

Bottom Line: Interestingly, recently emerged orphans are more likely to be lost than older ones.Furthermore, highly expressed orphans with a strong male-bias are more likely to be retained.Since both lost and retained orphans show similar evolutionary signatures of functional conservation, we propose that orphan loss is not driven by high rates of sequence evolution, but reflects lineage-specific functional requirements.

View Article: PubMed Central - PubMed

Affiliation: Institut für Populationsgenetik, Vetmeduni Vienna, Vienna, Austria.

ABSTRACT
Orphans are genes restricted to a single phylogenetic lineage and emerge at high rates. While this predicts an accumulation of genes, the gene number has remained remarkably constant through evolution. This paradox has not yet been resolved. Because orphan genes have been mainly analyzed over long evolutionary time scales, orphan loss has remained unexplored. Here we study the patterns of orphan turnover among close relatives in the Drosophila obscura group. We show that orphans are not only emerging at a high rate, but that they are also rapidly lost. Interestingly, recently emerged orphans are more likely to be lost than older ones. Furthermore, highly expressed orphans with a strong male-bias are more likely to be retained. Since both lost and retained orphans show similar evolutionary signatures of functional conservation, we propose that orphan loss is not driven by high rates of sequence evolution, but reflects lineage-specific functional requirements. DOI: http://dx.doi.org/10.7554/eLife.01311.001.

No MeSH data available.


Related in: MedlinePlus

Schematic tree of the Drosophila species analyzed in this study.The tree includes the 12 Drosophila species from FlyBase (Clark et al., 2007) plus three additional members of the obscura group (D. affinis, D. lowei, and D. miranda). The obscura group is highlighted in magenta. The species corresponding to the black subtrees were used as outgroups in the orphan detection pipeline (see ‘Materials and methods’). Divergence times for the 12 Drosophila species are taken from Table 3 in Obbard et al. (2012) (estimates based on mutation rate); for D. affinis and D. miranda from Gao et al. (2007); for D. lowei from Beckenbach et al. (1993).DOI:http://dx.doi.org/10.7554/eLife.01311.011
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3927632&req=5

fig6s1: Schematic tree of the Drosophila species analyzed in this study.The tree includes the 12 Drosophila species from FlyBase (Clark et al., 2007) plus three additional members of the obscura group (D. affinis, D. lowei, and D. miranda). The obscura group is highlighted in magenta. The species corresponding to the black subtrees were used as outgroups in the orphan detection pipeline (see ‘Materials and methods’). Divergence times for the 12 Drosophila species are taken from Table 3 in Obbard et al. (2012) (estimates based on mutation rate); for D. affinis and D. miranda from Gao et al. (2007); for D. lowei from Beckenbach et al. (1993).DOI:http://dx.doi.org/10.7554/eLife.01311.011

Mentions: Orphans are commonly detected by BLASTing the genes of a given organism against a set of outgroup species (Domazet-Loso and Tautz, 2003; Toll-Riera et al., 2009). A BLASTP cutoff of 10−3–10−4 was found to be optimal to maximize sensitivity and specificity in Drosophila (Domazet-Loso and Tautz, 2003). To identify orphans we used a BLASTP cutoff of 10−4 combined with a TBLASTN cutoff of 10−4, to exclude genes with unannotated orthologs in other species. Following these criteria, we searched in Drosophila pseudoobscura for genes with no sequence conservation in 10 Drosophila species outside the Drosophila obscura group (Figure 6—figure supplement 1). In total, we identified 1152 orphans, corresponding to 7% of all the D. pseudoobscura genes. Our estimate is slightly lower than a previous one (Zhang et al., 2010), due to our different filtering procedure, but still consistent with a high rate of orphan gain in Drosophila (Domazet-Loso and Tautz, 2003; Domazet-Loso et al., 2007; Zhou et al., 2008; Wissler et al., 2013). Our data clearly indicate that orphan genes are subject to purifying selection, as they show several hallmarks of functional protein-coding sequences (Figures 1, 2). A comparison of orphan genes preserved between D. pseudoobscura and D. affinis resulted in a distribution of dN/dS significantly lower than 1 with a median of 0.44 (Figure 1—figure supplement 1, one-sided Wilcoxon signed-rank test, p<1.0 × 10−15), as expected for protein-coding sequences. Moreover, dN/dS for orphans is significantly lower (Mann–Whitney test, p=2.7 × 10−14) than dN/dS calculated on a random set of intergenic regions with the same length distribution of orphans (see ‘Materials and methods’, section ‘Evolutionary rates’) (Figure 1A). Consistent with this, we also found orphans to be more conserved than intergenic regions (Figure 1B, Figure 1—figure supplement 2). The codon usage bias of orphans is intermediate to that of old genes and intergenic regions (Figure 1C).10.7554/eLife.01311.003Figure 1.Orphans are subject to purifying selection.


The life cycle of Drosophila orphan genes.

Palmieri N, Kosiol C, Schlötterer C - Elife (2014)

Schematic tree of the Drosophila species analyzed in this study.The tree includes the 12 Drosophila species from FlyBase (Clark et al., 2007) plus three additional members of the obscura group (D. affinis, D. lowei, and D. miranda). The obscura group is highlighted in magenta. The species corresponding to the black subtrees were used as outgroups in the orphan detection pipeline (see ‘Materials and methods’). Divergence times for the 12 Drosophila species are taken from Table 3 in Obbard et al. (2012) (estimates based on mutation rate); for D. affinis and D. miranda from Gao et al. (2007); for D. lowei from Beckenbach et al. (1993).DOI:http://dx.doi.org/10.7554/eLife.01311.011
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3927632&req=5

fig6s1: Schematic tree of the Drosophila species analyzed in this study.The tree includes the 12 Drosophila species from FlyBase (Clark et al., 2007) plus three additional members of the obscura group (D. affinis, D. lowei, and D. miranda). The obscura group is highlighted in magenta. The species corresponding to the black subtrees were used as outgroups in the orphan detection pipeline (see ‘Materials and methods’). Divergence times for the 12 Drosophila species are taken from Table 3 in Obbard et al. (2012) (estimates based on mutation rate); for D. affinis and D. miranda from Gao et al. (2007); for D. lowei from Beckenbach et al. (1993).DOI:http://dx.doi.org/10.7554/eLife.01311.011
Mentions: Orphans are commonly detected by BLASTing the genes of a given organism against a set of outgroup species (Domazet-Loso and Tautz, 2003; Toll-Riera et al., 2009). A BLASTP cutoff of 10−3–10−4 was found to be optimal to maximize sensitivity and specificity in Drosophila (Domazet-Loso and Tautz, 2003). To identify orphans we used a BLASTP cutoff of 10−4 combined with a TBLASTN cutoff of 10−4, to exclude genes with unannotated orthologs in other species. Following these criteria, we searched in Drosophila pseudoobscura for genes with no sequence conservation in 10 Drosophila species outside the Drosophila obscura group (Figure 6—figure supplement 1). In total, we identified 1152 orphans, corresponding to 7% of all the D. pseudoobscura genes. Our estimate is slightly lower than a previous one (Zhang et al., 2010), due to our different filtering procedure, but still consistent with a high rate of orphan gain in Drosophila (Domazet-Loso and Tautz, 2003; Domazet-Loso et al., 2007; Zhou et al., 2008; Wissler et al., 2013). Our data clearly indicate that orphan genes are subject to purifying selection, as they show several hallmarks of functional protein-coding sequences (Figures 1, 2). A comparison of orphan genes preserved between D. pseudoobscura and D. affinis resulted in a distribution of dN/dS significantly lower than 1 with a median of 0.44 (Figure 1—figure supplement 1, one-sided Wilcoxon signed-rank test, p<1.0 × 10−15), as expected for protein-coding sequences. Moreover, dN/dS for orphans is significantly lower (Mann–Whitney test, p=2.7 × 10−14) than dN/dS calculated on a random set of intergenic regions with the same length distribution of orphans (see ‘Materials and methods’, section ‘Evolutionary rates’) (Figure 1A). Consistent with this, we also found orphans to be more conserved than intergenic regions (Figure 1B, Figure 1—figure supplement 2). The codon usage bias of orphans is intermediate to that of old genes and intergenic regions (Figure 1C).10.7554/eLife.01311.003Figure 1.Orphans are subject to purifying selection.

Bottom Line: Interestingly, recently emerged orphans are more likely to be lost than older ones.Furthermore, highly expressed orphans with a strong male-bias are more likely to be retained.Since both lost and retained orphans show similar evolutionary signatures of functional conservation, we propose that orphan loss is not driven by high rates of sequence evolution, but reflects lineage-specific functional requirements.

View Article: PubMed Central - PubMed

Affiliation: Institut für Populationsgenetik, Vetmeduni Vienna, Vienna, Austria.

ABSTRACT
Orphans are genes restricted to a single phylogenetic lineage and emerge at high rates. While this predicts an accumulation of genes, the gene number has remained remarkably constant through evolution. This paradox has not yet been resolved. Because orphan genes have been mainly analyzed over long evolutionary time scales, orphan loss has remained unexplored. Here we study the patterns of orphan turnover among close relatives in the Drosophila obscura group. We show that orphans are not only emerging at a high rate, but that they are also rapidly lost. Interestingly, recently emerged orphans are more likely to be lost than older ones. Furthermore, highly expressed orphans with a strong male-bias are more likely to be retained. Since both lost and retained orphans show similar evolutionary signatures of functional conservation, we propose that orphan loss is not driven by high rates of sequence evolution, but reflects lineage-specific functional requirements. DOI: http://dx.doi.org/10.7554/eLife.01311.001.

No MeSH data available.


Related in: MedlinePlus