Assessing Conservation of Alternative Splicing with Evolutionary Splicing Graphs

Overview

Journal Genome Res

Specialty Genetics

Date 2021 Jul 16

PMID 34266979

Citations 3

Authors

Diego Javier Zea

Sofya Laskina

Alexis Baudin

Hugues Richard

Elodie Laine

Affiliations

Soon will be listed here.

Abstract

Understanding how protein function has evolved and diversified is of great importance for human genetics and medicine. Here, we tackle the problem of describing the whole transcript variability observed in several species by generalizing the definition of splicing graph. We provide a practical solution to construct parsimonious evolutionary splicing graphs where each node is a minimal transcript building block defined across species. We show a clear link between the functional relevance, tissue regulation, and conservation of alternative transcripts on a set of 50 genes. By scaling up to the whole human protein-coding genome, we identify a few thousand genes where alternative splicing modulates the number and composition of pseudorepeats. We have implemented our approach in ThorAxe, an efficient, versatile, robust, and freely available computational tool.

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References

Sultan M, Schulz M, Richard H, Magen A, Klingenhoff A, Scherf M . A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Science. 2008; 321(5891):956-60. DOI: 10.1126/science.1160342. View

Bhattacharyya M, Lee Y, Muratcioglu S, Qiu B, Nyayapati P, Schulman H . Flexible linkers in CaMKII control the balance between activating and inhibitory autophosphorylation. Elife. 2020; 9. PMC: 7141811. DOI: 10.7554/eLife.53670. View

Siepel A, Bejerano G, Pedersen J, Hinrichs A, Hou M, Rosenbloom K . Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 2005; 15(8):1034-50. PMC: 1182216. DOI: 10.1101/gr.3715005. View

Szalkowski A . Fast and robust multiple sequence alignment with phylogeny-aware gap placement. BMC Bioinformatics. 2012; 13:129. PMC: 3495709. DOI: 10.1186/1471-2105-13-129. View

Ward A, Cooper T . The pathobiology of splicing. J Pathol. 2009; 220(2):152-63. PMC: 2855871. DOI: 10.1002/path.2649. View

Wang G, Cooper T . Splicing in disease: disruption of the splicing code and the decoding machinery. Nat Rev Genet. 2007; 8(10):749-61. DOI: 10.1038/nrg2164. View

Mei W, Boatwright L, Feng G, Schnable J, Barbazuk W . Evolutionarily Conserved Alternative Splicing Across Monocots. Genetics. 2017; 207(2):465-480. PMC: 5629316. DOI: 10.1534/genetics.117.300189. View

Ezkurdia I, Rodriguez J, Pau E, Vazquez J, Valencia A, Tress M . Most highly expressed protein-coding genes have a single dominant isoform. J Proteome Res. 2015; 14(4):1880-7. PMC: 4768900. DOI: 10.1021/pr501286b. View

Bjorklund A, Light S, Sagit R, Elofsson A . Nebulin: a study of protein repeat evolution. J Mol Biol. 2010; 402(1):38-51. DOI: 10.1016/j.jmb.2010.07.011. View

10.

Greenberg M, Ostap E . Regulation and control of myosin-I by the motor and light chain-binding domains. Trends Cell Biol. 2012; 23(2):81-9. PMC: 3558615. DOI: 10.1016/j.tcb.2012.10.008. View

11.

Yates A, Akanni W, Amode M, Barrell D, Billis K, Carvalho-Silva D . Ensembl 2016. Nucleic Acids Res. 2015; 44(D1):D710-6. PMC: 4702834. DOI: 10.1093/nar/gkv1157. View

12.

Weatheritt R, Sterne-Weiler T, Blencowe B . The ribosome-engaged landscape of alternative splicing. Nat Struct Mol Biol. 2016; 23(12):1117-1123. PMC: 5295628. DOI: 10.1038/nsmb.3317. View

13.

Byrne A, Cole C, Volden R, Vollmers C . Realizing the potential of full-length transcriptome sequencing. Philos Trans R Soc Lond B Biol Sci. 2019; 374(1786):20190097. PMC: 6792442. DOI: 10.1098/rstb.2019.0097. View

14.

Brocke L, Srinivasan M, Schulman H . Developmental and regional expression of multifunctional Ca2+/calmodulin-dependent protein kinase isoforms in rat brain. J Neurosci. 1995; 15(10):6797-808. PMC: 6578007. View

15.

Marti-Solano M, Crilly S, Malinverni D, Munk C, Harris M, Pearce A . Author Correction: Combinatorial expression of GPCR isoforms affects signalling and drug responses. Nature. 2020; 588(7838):E24. DOI: 10.1038/s41586-020-2999-9. View

16.

Park E, Pan Z, Zhang Z, Lin L, Xing Y . The Expanding Landscape of Alternative Splicing Variation in Human Populations. Am J Hum Genet. 2018; 102(1):11-26. PMC: 5777382. DOI: 10.1016/j.ajhg.2017.11.002. View

17.

De La Grange P, Gratadou L, Delord M, Dutertre M, Auboeuf D . Splicing factor and exon profiling across human tissues. Nucleic Acids Res. 2010; 38(9):2825-38. PMC: 2875023. DOI: 10.1093/nar/gkq008. View

18.

Baralle F, Giudice J . Alternative splicing as a regulator of development and tissue identity. Nat Rev Mol Cell Biol. 2017; 18(7):437-451. PMC: 6839889. DOI: 10.1038/nrm.2017.27. View

19.

Sterne-Weiler T, Weatheritt R, Best A, Ha K, Blencowe B . Efficient and Accurate Quantitative Profiling of Alternative Splicing Patterns of Any Complexity on a Laptop. Mol Cell. 2018; 72(1):187-200.e6. DOI: 10.1016/j.molcel.2018.08.018. View

20.

Kelemen O, Convertini P, Zhang Z, Wen Y, Shen M, Falaleeva M . Function of alternative splicing. Gene. 2012; 514(1):1-30. PMC: 5632952. DOI: 10.1016/j.gene.2012.07.083. View