Liu Ting, Lin Kui
College of Life Sciences, Beijing Normal University, No. 19, Xinjiekouwai Street, Haidian District, Beijing, 100875, P. R. China.
Mol Biosyst. 2015 May;11(5):1378-88. doi: 10.1039/c5mb00132c.
By enabling the transcription of multiple isoforms from the same gene locus, alternative-splicing mechanisms greatly expand the diversity of the human transcriptome and proteome. Currently, the alternatively spliced transcripts from each protein-coding gene locus in the human genome can be classified as either principal or non-principal isoforms, providing that they differ with respect to cross-species conservation or biological features. By mapping the variants from the 1000 Genomes Project onto the coding region of each isoform, an interesting pattern of the genetic variation distributions of the coding regions for these two types of transcript isoforms was revealed on a whole-genome scale: compared with the principal isoform-specific coding regions, the non-principal isoform-specific coding regions are significantly enriched in amino acid-changing variants, particularly those that have a strong impact on protein function and have higher derived allele frequencies, suggesting that non-principal isoform-specific substitutions are less likely to be related to phenotype changes or disease. The results herein can help us better understand the potential consequences of alternatively spliced products from a population perspective.
通过使同一基因座转录多种异构体，可变剪接机制极大地扩展了人类转录组和蛋白质组的多样性。目前，人类基因组中每个蛋白质编码基因座的可变剪接转录本可分为主要异构体或非主要异构体，前提是它们在跨物种保守性或生物学特征方面存在差异。通过将千人基因组计划的变异映射到每个异构体的编码区域，在全基因组规模上揭示了这两种类型转录本异构体编码区域遗传变异分布的有趣模式：与主要异构体特异性编码区域相比，非主要异构体特异性编码区域在改变氨基酸的变异中显著富集，特别是那些对蛋白质功能有强烈影响且衍生等位基因频率较高的变异，这表明非主要异构体特异性替代不太可能与表型变化或疾病相关。本文的结果有助于我们从群体角度更好地理解可变剪接产物的潜在后果。
