Evolution of orphan genes in Drosophila

Orphan genes are protein coding regions that have no recognizable homologue in distantly related species. A substantial fraction of coding regions in any genome sequenced so far consists of such orphan genes, but their evolutionary and functional significance is not understood. A re-analysis of the Drosophila melanogaster proteome is presented that shows that there are still between 26 - 29% of all proteins without a significant match with non-insect sequences. Therefore, neither the growth of the database nor the re-annotations have significantly changed the proportion of orphans in the Drosophila genome over time. In addition, it was shown that these orphans are significantly underrepresented in the current genetic analysis. To analyse directly the evolutionary characteristics of orphan genes in Drosophila, 774 sequences were compared between cDNAs retrieved from two D. yakuba libraries (embryo and adult) and their corresponding D. melanogaster orthologues. Analysis of substitution rates shows that recovered orphans evolve on average more than three times faster than non-orphan genes, although the width of the evolutionary rate distribution is similar for both classes. In particular, some orphan genes show very low substitution rates, which are comparable to otherwise highly, conserved genes. A general model for orphan gene evolution is proposed that takes these large rate differences into account and suggests that they are caused by episodic phases of fast and slow divergence. Besides the result, that orphans are under-represented among genetically studied genes, additional findings suggest that orphan genes have less obvious phenotypes. For example, in the complete sample of the recovered cDNAs higher frequency of genetically studied genes was found among slow evolving genes, what supports the proposed hypothesis that functionally more important genes with obvious phenotypes have lower evolutionary rates. Interestingly, such relationship is lacking if only orphans are analysed. Additionally, orphans are over-represented among genes related to olfaction, hormonal activity, puparial adhesion, egg membrane structure and perception and response to abiotic stimulus. It is reasonable to expect for all of these functions to be involved in specific ecological adaptations that change easily over time, and accordingly to have mutant phenotypes which are difficult to detect. Finally, comparison between stages shows that the cDNA library from adults yields twice as many orphan genes than the one from embryos. An analysis of only genes having stage specific expression reveals a similar figure and together with lower evolutionary rate of embryo transcripts suggests a higher constraint on use of orphan genes in embryos. Furthermore, expression of embryo orphans is more often spatially restricted compared to a random sample of genes what shows that they act in more localised rather then ubiquitous manner. Taken together, the general characteristics of orphan genes in Drosophila suggest that they may be involved in the evolution of adaptive traits and that slow evolving orphan genes may be particularly interesting candidate genes for identifying lineage specific adaptations

Limits of Homology Detection By Pairwise Sequence Comparison

Motivation: Noise in database searches resulting from random sequences similarities increases as the databases expand rapidly. The noise problems are not a technical shortcoming of the database search programs, but a logical consequence of the idea of homology searches. The effect can be observed in simulation experiments. Results: We have investigated noise levels in pairwise alignment based database searches. The noise levels of 38 releases of the SwissProt database, display perfect logarithmic growth with the total length of the databases. Clustering of real biological sequences reduces noise levels, but the effect is marginal