Correspondence of D. melanogaster and C. elegans developmental stages revealed by alternative splicing characteristics of conserved exons

Ruiqi Gao, Jingyi Jessica Li

We report a statistical study to find correspondence of D. melanogaster and C. elegans developmental stages based on alternative splicing (AS) characteristics of conserved cassette exons using modENCODE RNA-seq data. We identify "stage-associated exons" to capture the AS characteristics of each stage and use these exons to map pairwise stages within and between the two species by an overlap test. Within fly and worm, adjacent developmental stages are mapped to each other, i.e., a strong diagonal pattern is observed as expected, supporting the validity of our approach. Between fly and worm, two parallel mapping patterns are observed between fly early embryos to early larvae and worm life cycle, and between fly late larvae to adults and worm late embryos to adults. We also apply this approach to compare tissues and cells from fly and worm. Findings include the high similarity between fly/worm adults and fly/worm embryos, groupings of fly cell lines, and strong mappings of fly head tissues to worm late embryos and male adults. Gene ontology and KEGG enrichment analyses provide a detailed functional annotation of the identified stage-associated exons, as well as a functional explanation of the observed correspondence map between fly and worm developmental stages. Our results suggest that AS dynamics of the exon pairs that share similar DNA sequences are informative for finding transcriptomic similarity of biological samples. Our study is innovative in two aspects. First, to our knowledge, our study is the first comprehensive study of AS events in fly and worm developmental stages, tissues, and cells. AS events provide an alternative perspective of transcriptome dynamics, compared to gene expression events. Second, our results do not entirely rely on the information of orthologous genes. Interesting results are also observed for fly and worm cassette exon pairs with DNA sequence similarity but not in orthologous gene pairs.