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

Yue Y, Meng Y, Ma H, Hou S, Cao G, Hong W, Shi Y, Guo P, Liu B, Shi F, Yang Y, Jin Y - Nat Commun (2016)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biochemistry, Innovation Center for Signaling Network, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang ZJ310058, China.

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.

No MeSH data available.


Related in: MedlinePlus

Organization of two novel Dscam gene subfamilies in M. martensii.(a) Organization of the sDscamα gene. The sDscamα gene is composed of multiple tandemly arrayed regions (indicated by the coloured boxes) and common region exons (indicated by the black boxes). ‘()' represents the number of tandem cassettes. The arrows indicate the transcription start sites. FNIII, fibronectin III domains; Ig, immunoglobulin domains. The N-terminal small boxes represent the leader peptides. The grey and black boxes represent the transmembrane (TM) and cytoplasmic domains, respectively. These cassettes are composed of two exons (indicated by the coloured boxes). Each variable cassette was transcribed by an alternative promoter followed by alternative splicing. The sDscamα variable cassette encoded the N-terminal Ig1 (blue), which corresponded to the variable Ig7 domain of Drosophila Dscam1. (b) Organization of the sDscamβ genes. This sDscamβ subfamily was composed of six members (sDscamβ1–sDscamβ6), 5′ tandem cassettes of which generally contained four exons. The variable cassette encoded the N-terminal Ig1+2 domains (coloured), which corresponded to the variable Ig7+8 domains of Drosophila Dscam1.
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f1: Organization of two novel Dscam gene subfamilies in M. martensii.(a) Organization of the sDscamα gene. The sDscamα gene is composed of multiple tandemly arrayed regions (indicated by the coloured boxes) and common region exons (indicated by the black boxes). ‘()' represents the number of tandem cassettes. The arrows indicate the transcription start sites. FNIII, fibronectin III domains; Ig, immunoglobulin domains. The N-terminal small boxes represent the leader peptides. The grey and black boxes represent the transmembrane (TM) and cytoplasmic domains, respectively. These cassettes are composed of two exons (indicated by the coloured boxes). Each variable cassette was transcribed by an alternative promoter followed by alternative splicing. The sDscamα variable cassette encoded the N-terminal Ig1 (blue), which corresponded to the variable Ig7 domain of Drosophila Dscam1. (b) Organization of the sDscamβ genes. This sDscamβ subfamily was composed of six members (sDscamβ1–sDscamβ6), 5′ tandem cassettes of which generally contained four exons. The variable cassette encoded the N-terminal Ig1+2 domains (coloured), which corresponded to the variable Ig7+8 domains of Drosophila Dscam1.

Mentions: To trace the origins of duplicated exons of the Dscam genes in Arthropoda, the exons encoding the Ig7 orthologues of Drosophila Dscam1 in the M. martensii genome were analysed. These Ig-coding exons were tandemly arrayed across the gene body, similar to Drosophila Dscam1. Nevertheless, RNA-seq analyses and sequencing of 5′ RACE (rapid-amplification of cDNA ends) products indicated that these transcripts shared no common upstream exons, and therefore, they might initiate immediately upstream of each variable exon (Fig. 1). Importantly, we believe this was located close to the transcription start sites for each variable exon, because a stop codon was generally located in the frame immediately upstream from the ATG initiation codon in each variable cassette (Supplementary Fig. 1). Last, computer-assisted and RNA-seq analyses revealed seven novel Dscam genes in M. martensii, which were characterized by tandemly arrayed 5′ cassettes (Fig. 1). Their encoding isoforms were similar to each other and to previously characterized Drosophila Dscam1, but all lacked the canonical Ig1–6,10 and FNIII 3–4, 6 domains present in classical DSCAM. We therefore designated these novel shortened Dscam genes as sDscam. Based on different units of tandemly arrayed 5′ cassettes, these sDscams could be subdivided into two closely related subfamilies, sDscamα and sDscamβ (Fig. 1a,b). The former (sDscamα) contained tandemly arrayed 5′ cassettes with 2 exons. This tandem cassette encoded a single Ig domain, which corresponded to the Ig7 of Drosophila Dscam1 (Fig. 1a). Genome-wide analyses revealed the presence of only one member of the sDscamα subfamily, which contained at least 40 tandem copies at the 5′ variable regions.


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

Yue Y, Meng Y, Ma H, Hou S, Cao G, Hong W, Shi Y, Guo P, Liu B, Shi F, Yang Y, Jin Y - Nat Commun (2016)

Organization of two novel Dscam gene subfamilies in M. martensii.(a) Organization of the sDscamα gene. The sDscamα gene is composed of multiple tandemly arrayed regions (indicated by the coloured boxes) and common region exons (indicated by the black boxes). ‘()' represents the number of tandem cassettes. The arrows indicate the transcription start sites. FNIII, fibronectin III domains; Ig, immunoglobulin domains. The N-terminal small boxes represent the leader peptides. The grey and black boxes represent the transmembrane (TM) and cytoplasmic domains, respectively. These cassettes are composed of two exons (indicated by the coloured boxes). Each variable cassette was transcribed by an alternative promoter followed by alternative splicing. The sDscamα variable cassette encoded the N-terminal Ig1 (blue), which corresponded to the variable Ig7 domain of Drosophila Dscam1. (b) Organization of the sDscamβ genes. This sDscamβ subfamily was composed of six members (sDscamβ1–sDscamβ6), 5′ tandem cassettes of which generally contained four exons. The variable cassette encoded the N-terminal Ig1+2 domains (coloured), which corresponded to the variable Ig7+8 domains of Drosophila Dscam1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835542&req=5

f1: Organization of two novel Dscam gene subfamilies in M. martensii.(a) Organization of the sDscamα gene. The sDscamα gene is composed of multiple tandemly arrayed regions (indicated by the coloured boxes) and common region exons (indicated by the black boxes). ‘()' represents the number of tandem cassettes. The arrows indicate the transcription start sites. FNIII, fibronectin III domains; Ig, immunoglobulin domains. The N-terminal small boxes represent the leader peptides. The grey and black boxes represent the transmembrane (TM) and cytoplasmic domains, respectively. These cassettes are composed of two exons (indicated by the coloured boxes). Each variable cassette was transcribed by an alternative promoter followed by alternative splicing. The sDscamα variable cassette encoded the N-terminal Ig1 (blue), which corresponded to the variable Ig7 domain of Drosophila Dscam1. (b) Organization of the sDscamβ genes. This sDscamβ subfamily was composed of six members (sDscamβ1–sDscamβ6), 5′ tandem cassettes of which generally contained four exons. The variable cassette encoded the N-terminal Ig1+2 domains (coloured), which corresponded to the variable Ig7+8 domains of Drosophila Dscam1.
Mentions: To trace the origins of duplicated exons of the Dscam genes in Arthropoda, the exons encoding the Ig7 orthologues of Drosophila Dscam1 in the M. martensii genome were analysed. These Ig-coding exons were tandemly arrayed across the gene body, similar to Drosophila Dscam1. Nevertheless, RNA-seq analyses and sequencing of 5′ RACE (rapid-amplification of cDNA ends) products indicated that these transcripts shared no common upstream exons, and therefore, they might initiate immediately upstream of each variable exon (Fig. 1). Importantly, we believe this was located close to the transcription start sites for each variable exon, because a stop codon was generally located in the frame immediately upstream from the ATG initiation codon in each variable cassette (Supplementary Fig. 1). Last, computer-assisted and RNA-seq analyses revealed seven novel Dscam genes in M. martensii, which were characterized by tandemly arrayed 5′ cassettes (Fig. 1). Their encoding isoforms were similar to each other and to previously characterized Drosophila Dscam1, but all lacked the canonical Ig1–6,10 and FNIII 3–4, 6 domains present in classical DSCAM. We therefore designated these novel shortened Dscam genes as sDscam. Based on different units of tandemly arrayed 5′ cassettes, these sDscams could be subdivided into two closely related subfamilies, sDscamα and sDscamβ (Fig. 1a,b). The former (sDscamα) contained tandemly arrayed 5′ cassettes with 2 exons. This tandem cassette encoded a single Ig domain, which corresponded to the Ig7 of Drosophila Dscam1 (Fig. 1a). Genome-wide analyses revealed the presence of only one member of the sDscamα subfamily, which contained at least 40 tandem copies at the 5′ variable regions.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biochemistry, Innovation Center for Signaling Network, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang ZJ310058, China.

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.

No MeSH data available.


Related in: MedlinePlus