Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA.
PLoS Genet. 2011 Nov;7(11):e1002352. doi: 10.1371/journal.pgen.1002352. Epub 2011 Nov 3.
Arabidopsis TSO1 encodes a protein with conserved CXC domains known to bind DNA and is homologous to animal proteins that function in chromatin complexes. tso1 mutants fall into two classes due to their distinct phenotypes. Class I, represented by two different missense mutations in the CXC domain, leads to failure in floral organ development, sterility, and fasciated inflorescence meristems. Class II, represented by a nonsense mutation and a T-DNA insertion line, develops wild-type-like flowers and inflorescences but shows severely reduced fertility. The phenotypic variability of tso1 alleles presents challenges in determining the true function of TSO1. In this study, we use artificial microRNA, double mutant analysis, and bimolecular fluorescence complementation assay to investigate the molecular basis underlying these two distinct classes of phenotypes. We show that the class I mutants could be converted into class II by artificial microRNA knockdown of the tso1 mutant transcript, suggesting that class I alleles produce antimorphic mutant proteins that interfere with functionally redundant loci. We identified one such redundant factor coded by the closely related TSO1 homolog SOL2. We show that the class I phenotype can be mimicked by knocking out both TSO1 and its homolog SOL2 in double mutants. Such antimorphic alleles targeting redundant factors are likely prevalent in Arabidopsis and maybe common in organisms with many sets of paralogous genes such as human. Our data challenge the conventional view that recessive alleles are always hypomorphic or null and that antimorphic alleles are always dominant. This study shows that recessive alleles can also be antimorphic and can produce a phenotype more severe than null by interfering with the function of related loci. This finding adds a new paradigm to classical genetic concepts, with important implications for future genetic studies both in basic research as well as in agriculture and medicine.
拟南芥 TSO1 编码一种具有保守 CXC 结构域的蛋白质，该结构域已知能与 DNA 结合，并且与在染色质复合物中起作用的动物蛋白同源。tso1 突变体因其不同的表型可分为两类。第一类，由 CXC 结构域中的两个不同错义突变引起，导致花器官发育失败、不育和束状花序分生组织。第二类，由无义突变和 T-DNA 插入系代表，表现出与野生型相似的花和花序，但育性严重降低。tso1 等位基因的表型可变性给确定 TSO1 的真正功能带来了挑战。在这项研究中，我们使用人工 microRNA、双突变体分析和双分子荧光互补测定来研究这两种不同表型类别的分子基础。我们表明，通过人工 microRNA 敲低 tso1 突变体转录本，第一类突变体可以转化为第二类，这表明第一类等位基因产生了抗形突变蛋白，干扰了功能冗余的基因座。我们鉴定出一个这样的冗余因子，由密切相关的 TSO1 同源物 SOL2 编码。我们表明，在双突变体中敲除 TSO1 和其同源物 SOL2 可以模拟第一类表型。针对冗余因子的这种抗形等位基因可能在拟南芥中很常见，在具有许多套同源基因的生物体中也可能很常见，如人类。我们的数据挑战了隐性等位基因总是次等位基因或无效，并且抗形等位基因总是显性的传统观点。这项研究表明，隐性等位基因也可以是抗形的，并且通过干扰相关基因座的功能，产生比无效更严重的表型。这一发现为经典遗传概念增添了一个新的范例，对未来的基础研究以及农业和医学中的遗传研究都具有重要意义。
