PDF(Pubmed)
Abstract：
There are about 14,000 pseudogenes that are mutated or truncated sequences resembling functional parent genes. About two-thirds of pseudogenes are processed, while others are duplicated. Although initially thought dead, emerging studies indicate they have functional and regulatory roles. We study 14-3-3ζ, an adaptor protein that regulates cytokine signaling and inflammatory diseases, including rheumatoid arthritis, cancer, and neurological disorders. To understand how 14-3-3ζ (gene symbol YWHAZ) performs diverse functions, we examined the human genome and identified nine YWHAZ pseudogenes spread across many chromosomes. Unlike the 32 kb exon-to-exon sequence in YWHAZ, all pseudogenes are much shorter and lack introns. Out of six, four YWHAZ exons are highly conserved, but the untranslated region (UTR) shows significant diversity. The putative amino acid sequence of pseudogenes is 78-97% homologous, resulting in striking structural similarities with the parent protein. The OMIM and Decipher database searches revealed chromosomal loci containing pseudogenes are associated with human diseases that overlap with the parent gene. To the best of our knowledge, this is the first report on pseudogenes of the 14-3-3 family protein and their implications for human health. This bioinformatics-based study introduces a new insight into the complexity of 14-3-3ζ\'s functions in biology.
摘要：
大约有14,000个假基因是类似于功能性亲本基因的突变或截短序列。大约三分之二的假基因经过加工，而其他人是重复的。虽然最初以为死了，新兴研究表明，它们具有功能和调节作用。我们研究14-3-3ζ，一种调节细胞因子信号传导和炎性疾病的衔接蛋白，包括类风湿性关节炎,癌症,和神经系统疾病。要了解14-3-3ζ（基因符号YWHAZ）如何执行不同的功能，我们检查了人类基因组,鉴定了9个分布在许多染色体上的YWHAZ假基因.与YWHAZ中的32kb外显子到外显子序列不同，所有假基因都短得多，缺乏内含子。六个人中,四个YWHAZ外显子高度保守，但非翻译区(UTR)表现出显著的多样性。假基因的推定氨基酸序列有78-97%的同源性,导致与母体蛋白质惊人的结构相似性。OMIM和Decipher数据库搜索显示，含有假基因的染色体基因座与与亲本基因重叠的人类疾病有关。据我们所知,这是有关14-3-3家族蛋白的假基因及其对人类健康的影响的第一份报告。这项基于生物信息学的研究为14-3-3ζ在生物学中的功能的复杂性带来了新的见解。
