人类基因组的基因进化

生物谷

        在11月13日的《美国科学院院刊》的网站上公示了美国健康研究院癌症研究所的华人学者刘秀芬（Xiu-Fen  Liu）等人有关人类基因组中POTE-actin基因表达和进化的研究论文。

        研究组之前曾描述了一种灵长类特异性基因家族POTE，这种基因在许多中癌症中表达，但正常器官中的量很有限。

        13个POTE基因分散在8个不同的染色体中，并且由一个原始的基因ANKRD26经由人类基因组的扩增和重组进化形成。

        依据序列相似性，POTE基因家族成员分为三类。通过对基因组数据库进行分析，这个研究组在祖先POTE横向同源物（Paralog）的一个羧基末端确定出一种肌动蛋白反转录转座子插入。

        通过Northern  blot分析，研究人员在一种乳腺癌细胞系中确定出了假想的7.5-kb  POTE-actin转录本。由这种POTE-actin转录本编码的蛋白质被推测为一种120Da的蛋白。

        利用能够识别POTE蛋白的氨基酸末端部分的抗-POTE  mAbs，研究人员真的在乳腺癌细胞系（已知表达这种融合转录本）中检测到了这种120Da  POTE-actin融合蛋白。

        这些数据证明一种反转录转座子的插入早就了一种不同功能的POTE基因——这意味着通过反转录转座子的插入得以进化出新功能的人类基因。

英文原文：

Evolution and expression of chimeric POTE-actin genes in the human genome.

We previously described a primate-specific gene family, POTE, that is expressed in many cancers but in a limited number of normal organs. The 13 POTE genes are dispersed among eight different chromosomes and evolved by duplications and remodeling of the human genome from an ancestral gene, ANKRD26. Based on sequence similarity, the POTE gene family members can be divided into three groups. By genome database searches, we identified an actin retroposon insertion at the carboxyl terminus of one of the ancestral POTE paralogs. By Northern blot analysis, we identified the expected 7.5-kb POTE-actin chimeric transcript in a breast cancer cell line. The protein encoded by the POTE-actin transcript is predicted to be 120 kDa in size. Using anti-POTE mAbs that recognize the amino-terminal portion of the POTE protein, we detected the 120-kDa POTE-actin fusion protein in breast cancer cell lines known to express the fusion transcript. These data demonstrate that insertion of a retroposon produced an altered functional POTE gene. This example indicates that new functional human genes can evolve by insertion of retroposons.