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Natural variation of gene models in Drosophila melanogaster.

Kurmangaliyev YZ, Favorov AV, Osman NM, Lehmann KV, Campo D, Salomon MP, Tower J, Gelfand MS, Nuzhdin SV - BMC Genomics (2015)

Bottom Line: Allelic-imbalance in splicing patterns confirmed that the majority are regulated mainly by cis-genetic effects.The observed variation in splicing patterns are predicted to have limited effects on the encoded protein sequences.To our knowledge, this is the first sQTL mapping study in Drosophila.

View Article: PubMed Central - PubMed

Affiliation: University of Southern California, Los Angeles, CA, USA. kurmanga@usc.edu.

ABSTRACT

Background: Variation within splicing regulatory sequences often leads to differences in gene models among individuals within a species. Two alleles of the same gene may express transcripts with different exon/intron structures and consequently produce functionally different proteins. Matching genomic and transcriptomic data allows us to identify putative regulatory variants associated with changes in splicing patterns.

Results: Here we analyzed natural variation of splicing patterns in the transcriptomes of 81 natural strains of Drosophila melanogaster with known genotypes. We identified dozens of genotype-specific splicing patterns associated with putative cis-splicing quantitative trait loci (sQTL). The majority of changes can be explained by mutations in splice sites. Allelic-imbalance in splicing patterns confirmed that the majority are regulated mainly by cis-genetic effects. Remarkably, allele-specific splicing changes often lead to qualitative changes in gene models, yielding many isoforms not previously annotated. The observed alterations are typically outside protein-coding regions or affect only very short protein segments.

Conclusions: Overall, the sets of gene models appear to be flexible within D. melanogaster populations. The observed variation in splicing patterns are predicted to have limited effects on the encoded protein sequences. To our knowledge, this is the first sQTL mapping study in Drosophila.

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Related in: MedlinePlus

Distributions of allele-specific ΔΨ-values. ΔΨ-values as calculated for natural allele-specific reads (ns-ΔΨ), for tester allele-specific reads (ts-ΔΨ) and for all reads (ΔΨ). Values were calculated for cis-sQTL with sufficient coverage for calculation of both values for at least one F1-hybrid for each variant.
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Fig5: Distributions of allele-specific ΔΨ-values. ΔΨ-values as calculated for natural allele-specific reads (ns-ΔΨ), for tester allele-specific reads (ts-ΔΨ) and for all reads (ΔΨ). Values were calculated for cis-sQTL with sufficient coverage for calculation of both values for at least one F1-hybrid for each variant.

Mentions: Unfortunately, due to the limited coverage by allele-specific reads, we were able to estimate ns-Ψ and ts-Ψ only for a fraction of detected genotype-specific splicing events. Both values for at least one F1-hybrid for each variant of the cis-sQTL was obtained for 36 cis-sQTL, which were associated with 17 genotype-specific splicing events. For these cis-sQTL, we calculated the allele-specific ΔΨ-values (ns-ΔΨ and ts-ΔΨ). The distributions of allele-specific ΔΨ-values are shown in Figure 5. On average, ns-ΔΨ-values were considerably higher than ΔΨ-values calculated for all reads, and the median of the ts-ΔΨ-values distribution is close to zero (Figure 5). In other words, almost all differences between splicing patterns associated with cis-sQTL are caused by changes in transcripts expressed from natural alleles. This suggests that the majority of identified genotype-specific splicing patterns indeed are regulated by cis-genetic effects. At the same time, in some cases allele-specific ΔΨ-values did not follow the optimal patterns that could be expected for cis-genetic regulation (i.e. ts-ΔΨ = 0). This might be caused by a variety of factors, including non-causative alleles, low coverage, or the influence of unknown additional genetic effects (e.g. trans-genetic regulation).Figure 5


Natural variation of gene models in Drosophila melanogaster.

Kurmangaliyev YZ, Favorov AV, Osman NM, Lehmann KV, Campo D, Salomon MP, Tower J, Gelfand MS, Nuzhdin SV - BMC Genomics (2015)

Distributions of allele-specific ΔΨ-values. ΔΨ-values as calculated for natural allele-specific reads (ns-ΔΨ), for tester allele-specific reads (ts-ΔΨ) and for all reads (ΔΨ). Values were calculated for cis-sQTL with sufficient coverage for calculation of both values for at least one F1-hybrid for each variant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4373058&req=5

Fig5: Distributions of allele-specific ΔΨ-values. ΔΨ-values as calculated for natural allele-specific reads (ns-ΔΨ), for tester allele-specific reads (ts-ΔΨ) and for all reads (ΔΨ). Values were calculated for cis-sQTL with sufficient coverage for calculation of both values for at least one F1-hybrid for each variant.
Mentions: Unfortunately, due to the limited coverage by allele-specific reads, we were able to estimate ns-Ψ and ts-Ψ only for a fraction of detected genotype-specific splicing events. Both values for at least one F1-hybrid for each variant of the cis-sQTL was obtained for 36 cis-sQTL, which were associated with 17 genotype-specific splicing events. For these cis-sQTL, we calculated the allele-specific ΔΨ-values (ns-ΔΨ and ts-ΔΨ). The distributions of allele-specific ΔΨ-values are shown in Figure 5. On average, ns-ΔΨ-values were considerably higher than ΔΨ-values calculated for all reads, and the median of the ts-ΔΨ-values distribution is close to zero (Figure 5). In other words, almost all differences between splicing patterns associated with cis-sQTL are caused by changes in transcripts expressed from natural alleles. This suggests that the majority of identified genotype-specific splicing patterns indeed are regulated by cis-genetic effects. At the same time, in some cases allele-specific ΔΨ-values did not follow the optimal patterns that could be expected for cis-genetic regulation (i.e. ts-ΔΨ = 0). This might be caused by a variety of factors, including non-causative alleles, low coverage, or the influence of unknown additional genetic effects (e.g. trans-genetic regulation).Figure 5

Bottom Line: Allelic-imbalance in splicing patterns confirmed that the majority are regulated mainly by cis-genetic effects.The observed variation in splicing patterns are predicted to have limited effects on the encoded protein sequences.To our knowledge, this is the first sQTL mapping study in Drosophila.

View Article: PubMed Central - PubMed

Affiliation: University of Southern California, Los Angeles, CA, USA. kurmanga@usc.edu.

ABSTRACT

Background: Variation within splicing regulatory sequences often leads to differences in gene models among individuals within a species. Two alleles of the same gene may express transcripts with different exon/intron structures and consequently produce functionally different proteins. Matching genomic and transcriptomic data allows us to identify putative regulatory variants associated with changes in splicing patterns.

Results: Here we analyzed natural variation of splicing patterns in the transcriptomes of 81 natural strains of Drosophila melanogaster with known genotypes. We identified dozens of genotype-specific splicing patterns associated with putative cis-splicing quantitative trait loci (sQTL). The majority of changes can be explained by mutations in splice sites. Allelic-imbalance in splicing patterns confirmed that the majority are regulated mainly by cis-genetic effects. Remarkably, allele-specific splicing changes often lead to qualitative changes in gene models, yielding many isoforms not previously annotated. The observed alterations are typically outside protein-coding regions or affect only very short protein segments.

Conclusions: Overall, the sets of gene models appear to be flexible within D. melanogaster populations. The observed variation in splicing patterns are predicted to have limited effects on the encoded protein sequences. To our knowledge, this is the first sQTL mapping study in Drosophila.

Show MeSH
Related in: MedlinePlus