Open Access Highly Accessed Research article

Assessment of orthologous splicing isoforms in human and mouse orthologous genes

Federico Zambelli1, Giulio Pavesi1, Carmela Gissi1, David S Horner1 and Graziano Pesole23*

Author Affiliations

1 Dipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italia

2 Istituto Biomembrane e Bioenergetica, Consiglio Nazionale delle Ricerche, via Amendola 165/A, 70125 Bari, Italia

3 Dipartimento di Biochimica e Biologia Molecolare "E. Quagliariello", Università degli Studi di Bari, Via Orabona 4, 70126 Bari, Italia

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BMC Genomics 2010, 11:534  doi:10.1186/1471-2164-11-534

Published: 1 October 2010

Abstract

Background

Recent discoveries have highlighted the fact that alternative splicing and alternative transcripts are the rule, rather than the exception, in metazoan genes. Since multiple transcript and protein variants expressed by the same gene are, by definition, structurally distinct and need not to be functionally equivalent, the concept of gene orthology should be extended to the transcript level in order to describe evolutionary relationships between structurally similar transcript variants. In other words, the identification of true orthology relationships between gene products now should progress beyond primary sequence and "splicing orthology", consisting in ancestrally shared exon-intron structures, is required to define orthologous isoforms at transcript level.

Results

As a starting step in this direction, in this work we performed a large scale human- mouse gene comparison with a twofold goal: first, to assess if and to which extent traditional gene annotations such as RefSeq capture genuine splicing orthology; second, to provide a more detailed annotation and quantification of true human-mouse orthologous transcripts defined as transcripts of orthologous genes exhibiting the same splicing patterns.

Conclusions

We observed an identical exon/intron structure for 32% of human and mouse orthologous genes. This figure increases to 87% using less stringent criteria for gene structure similarity, thus implying that for about 13% of the human RefSeq annotated genes (and about 25% of the corresponding transcripts) we could not identify any mouse transcript showing sufficient similarity to be confidently assigned as a splicing ortholog. Our data suggest that current gene and transcript data may still be rather incomplete - with several splicing variants still unknown. The observation that alternative splicing produces large numbers of alternative transcripts and proteins, some of them conserved across species and others truly species-specific, suggests that, still maintaining the conventional definition of gene orthology, a new concept of "splicing orthology" can be defined at transcript level.