原创力文档a comprehensive survey of human polymorphisms at conserved splice dinucleotides and its evolutionary relationship with alternative splicing人类在守恒的拼接二核苷酸多态性的全面调查与可变剪接及其进化关系.pdfVIP
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a comprehensive survey of human polymorphisms at conserved splice dinucleotides and its evolutionary relationship with alternative splicing人类在守恒的拼接二核苷酸多态性的全面调查与可变剪接及其进化关系
Shimada et al. BMC Evolutionary Biology 2010, 10:122
/1471-2148/10/122
R E S E A R C H A R T I C L E Open Access
Research article
A comprehensive survey of human polymorphisms
at conserved splice dinucleotides and its
evolutionary relationship with alternative splicing
1,2,3 2,4 1,2 1,5 1
Makoto K Shimada , Yosuke Hayakawa , Jun-ichi Takeda , Takashi Gojobori and Tadashi Imanishi*
Abstract
Background: Alternative splicing (AS) is a key molecular process that endows biological functions with diversity and
complexity. Generally, functional redundancy leads to the generation of new functions through relaxation of selective
pressure in evolution, as exemplified by duplicated genes. It is also known that alternatively spliced exons (ASEs) are
subject to relaxed selective pressure. Within consensus sequences at the splice junctions, the most conserved sites are
dinucleotides at both ends of introns (splice dinucleotides). However, a small number of single nucleotide
polymorphisms (SNPs) occur at splice dinucleotides. An intriguing question relating to the evolution of AS diversity is
whether mutations at splice dinucleotides are maintained as polymorphisms and produce diversity in splice patterns
within the human population. We therefore surveyed validated SNPs in the database dbSNP located at splice
dinucleotides of all human genes that are defined by the H-Invitational Database.
Results: We found 212 validated SNPs at splice dinucleotides (sdSNPs); these were confirmed to be consistent with the
GT-AG rule at either allele. Moreover, 53 of them were observed to neighbor ASEs (AE dinucleotides). No significant
differences were observed between sdSNPs at AE dinucleotides and those at consti
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