assessment of orthologous splicing isoforms in human and mouse orthologous genes评估同源拼接亚型在人类和小鼠同源基因.pdfVIP

Zambelli et al. BMC Genomics 2010, 11:534 /1471-2164/11/534 RESEARCH ARTICLE Open Access Assessment of orthologous splicing isoforms in human and mouse orthologous genes 1† 1† 1 1 2,3* Federico Zambelli , Giulio Pavesi , Carmela Gissi , David S Horner , Graziano Pesole 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