A large family of Dscam genes with tandemly arrayed 5′ cassettes in Chelicerata

Yuan Yue,Yun Yang,Weiling Hong,Guozheng Cao,Hongru Ma,Feng Shi,Pengjuan Guo,Baoping Liu,Yongfeng Jin,Shouqing Hou,Yijun Meng,Yang Shi

doi:10.1038/ncomms11252

Yuan Yue, Yun Yang + Show 10 more

Open Access

https://doi.org/10.1038/ncomms11252

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Abstract

Drosophila Dscam1 (Down Syndrome Cell Adhesion Molecules) and vertebrate clustered protocadherins (Pcdhs) are two classic examples of the extraordinary isoform diversity from a single genomic locus. Dscam1 encodes 38,016 distinct isoforms via mutually exclusive splicing in D. melanogaster, while the vertebrate clustered Pcdhs utilize alternative promoters to generate isoform diversity. Here we reveal a shortened Dscam gene family with tandemly arrayed 5′ cassettes in Chelicerata. These cassette repeats generally comprise two or four exons, corresponding to variable Immunoglobulin 7 (Ig7) or Ig7–8 domains of Drosophila Dscam1. Furthermore, extraordinary isoform diversity has been generated through a combination of alternating promoter and alternative splicing. These sDscams have a high sequence similarity with Drosophila Dscam1, and share striking organizational resemblance to the 5′ variable regions of vertebrate clustered Pcdhs. Hence, our findings have important implications for understanding the functional similarities between Drosophila Dscam1 and vertebrate Pcdhs, and may provide further mechanistic insights into the regulation of isoform diversity.

Highlights

Drosophila Dscam[1] (Down Syndrome Cell Adhesion Molecules) and vertebrate clustered protocadherins (Pcdhs) are two classic examples of the extraordinary protein isoform diversity that can arise from a single complex genomic locus in two phyla[3,4]
The encoded proteins had a striking similarity to Drosophila Dscam[1], but all lacked the canonical Immunoglobulin 1 (Ig1)–6, 10 and Fibronectin III (FNIII) 3–4, 6 domains present in classical DSCAM
Based on different units of tandemly arrayed 50 cassettes, these sDscams could be subdivided into two closely related subfamilies, sDscama and sDscamb (Fig. 1a,b). The former contained tandemly arrayed 50 cassettes with 2 exons. This tandem cassette encoded a single Ig domain, which corresponded to the Immunoglobulin 7 (Ig7) of Drosophila Dscam[1] (Fig. 1a)

Summary

Introduction

Drosophila Dscam[1] (Down Syndrome Cell Adhesion Molecules) and vertebrate clustered protocadherins (Pcdhs) are two classic examples of the extraordinary isoform diversity from a single genomic locus. Dscam[1] gene encodes 38,016 distinct isoforms via mutually exclusive alternative splicing of 4 arrays of tandem duplicated exons in D. melanogaster[3] These Dscam[1] isoforms are expressed stochastically and combinatorially, and exhibit isoform-specific homophilic binding[5,6,7,8,9,10]. 52 Pcdh proteins are encoded by 3 tightly linked gene clusters called Pcdha, Pcdhb and Pcdhg, which are organized in a tandem array and on a single chromosome[4] In these genes, each variable exon is preceded by a promoter, and Pcdh diversity is produced via differential promoter choice and cis-alternative splicing[19,20]. Our findings have important implications to aid in our understanding of the functional similarities between two structurally unrelated families of Drosophila Dscam and vertebrate Pcdhs, and may provide further insights into the regulatory mechanisms governing the selection of tandemly arrayed 50 variable regions

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