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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

Model of the origins of sDscamα and sDscamβ.Symbols used are the same as in Fig. 1. The sDscam gene may have originated from the sequential shortening and expansion of the Ig and FNIII domains of canonical Dscam. First, the ancestral Dscam gene underwent sequential shortening of the Ig and FNIII domains of canonical Dscam (marked by the red dashed box). Eventually, a shortened Dscam evolved in the ancestral gene. This sDscam ancestor was followed later by 5′ segmental duplication to create two or more tandemly arrayed cassettes. The duplication unit may have included both exons 1–2 encoding an Ig domain or exons 1–4 encoding 2 Ig domains and their promoters (green or blue dashed boxes). Thus, various isoforms with diverse Ig1 (sDscamα) and Ig1–2 (sDscamβ) were generated by combining alternative promoters with alternative splicing.
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f2: Model of the origins of sDscamα and sDscamβ.Symbols used are the same as in Fig. 1. The sDscam gene may have originated from the sequential shortening and expansion of the Ig and FNIII domains of canonical Dscam. First, the ancestral Dscam gene underwent sequential shortening of the Ig and FNIII domains of canonical Dscam (marked by the red dashed box). Eventually, a shortened Dscam evolved in the ancestral gene. This sDscam ancestor was followed later by 5′ segmental duplication to create two or more tandemly arrayed cassettes. The duplication unit may have included both exons 1–2 encoding an Ig domain or exons 1–4 encoding 2 Ig domains and their promoters (green or blue dashed boxes). Thus, various isoforms with diverse Ig1 (sDscamα) and Ig1–2 (sDscamβ) were generated by combining alternative promoters with alternative splicing.

Mentions: How the 5′ clustered organization of the sDscam gene arose was investigated next. Following a comprehensive comparative analysis of Dscam sequences from arthropod species (Supplementary Fig. 3), it was speculated that the sDscam gene might have originated from the sequential shortening and expansion of the Ig and FNIII domains of canonical Dscam (Fig. 2, Supplementary Fig. 4a). First, the ancestral Dscam gene underwent the loss of FNIII3–4 and Ig10 domains before the divergence of Arachnida and Merostomata. This is supported by the fact that Dscam genes lacking the FNIII3–4 and Ig10 domains are present in all Chelicerata species investigated (Supplementary Fig. 3). The further loss of the FNIII domain proximal to the transmembrane domain was followed later by the loss of the coding region encoding the N-terminal Ig1–6 domains (Fig. 2; Supplementary Fig. 4a). Eventually, a shortened Dscam evolved in the ancestral gene. Second, this shortening was followed later by 5′ segmental duplication to create two or multiple tandemly arrayed cassettes. The duplication unit may include both exons 1–2 encoding an Ig domain or exons 1–4 encoding two Ig domains and their promoters (green or blue dashed box, Fig. 2; Supplementary Fig. 4a). Moreover, phylogenetic analysis indicated that these clustered cassettes were more similar to each other than to the variable cassettes from other species (Supplementary Figs 5 and 6), suggesting that the variable cassettes were expanded in a species-specific manner.


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)

Model of the origins of sDscamα and sDscamβ.Symbols used are the same as in Fig. 1. The sDscam gene may have originated from the sequential shortening and expansion of the Ig and FNIII domains of canonical Dscam. First, the ancestral Dscam gene underwent sequential shortening of the Ig and FNIII domains of canonical Dscam (marked by the red dashed box). Eventually, a shortened Dscam evolved in the ancestral gene. This sDscam ancestor was followed later by 5′ segmental duplication to create two or more tandemly arrayed cassettes. The duplication unit may have included both exons 1–2 encoding an Ig domain or exons 1–4 encoding 2 Ig domains and their promoters (green or blue dashed boxes). Thus, various isoforms with diverse Ig1 (sDscamα) and Ig1–2 (sDscamβ) were generated by combining alternative promoters with alternative splicing.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Model of the origins of sDscamα and sDscamβ.Symbols used are the same as in Fig. 1. The sDscam gene may have originated from the sequential shortening and expansion of the Ig and FNIII domains of canonical Dscam. First, the ancestral Dscam gene underwent sequential shortening of the Ig and FNIII domains of canonical Dscam (marked by the red dashed box). Eventually, a shortened Dscam evolved in the ancestral gene. This sDscam ancestor was followed later by 5′ segmental duplication to create two or more tandemly arrayed cassettes. The duplication unit may have included both exons 1–2 encoding an Ig domain or exons 1–4 encoding 2 Ig domains and their promoters (green or blue dashed boxes). Thus, various isoforms with diverse Ig1 (sDscamα) and Ig1–2 (sDscamβ) were generated by combining alternative promoters with alternative splicing.
Mentions: How the 5′ clustered organization of the sDscam gene arose was investigated next. Following a comprehensive comparative analysis of Dscam sequences from arthropod species (Supplementary Fig. 3), it was speculated that the sDscam gene might have originated from the sequential shortening and expansion of the Ig and FNIII domains of canonical Dscam (Fig. 2, Supplementary Fig. 4a). First, the ancestral Dscam gene underwent the loss of FNIII3–4 and Ig10 domains before the divergence of Arachnida and Merostomata. This is supported by the fact that Dscam genes lacking the FNIII3–4 and Ig10 domains are present in all Chelicerata species investigated (Supplementary Fig. 3). The further loss of the FNIII domain proximal to the transmembrane domain was followed later by the loss of the coding region encoding the N-terminal Ig1–6 domains (Fig. 2; Supplementary Fig. 4a). Eventually, a shortened Dscam evolved in the ancestral gene. Second, this shortening was followed later by 5′ segmental duplication to create two or multiple tandemly arrayed cassettes. The duplication unit may include both exons 1–2 encoding an Ig domain or exons 1–4 encoding two Ig domains and their promoters (green or blue dashed box, Fig. 2; Supplementary Fig. 4a). Moreover, phylogenetic analysis indicated that these clustered cassettes were more similar to each other than to the variable cassettes from other species (Supplementary Figs 5 and 6), suggesting that the variable cassettes were expanded in a species-specific manner.

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