Department of Microbiology, The Ohio State University, Columbus, OH, United States of America.
Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv, Israel.
PLoS Genet. 2018 Apr 9;14(4):e1007326. doi: 10.1371/journal.pgen.1007326. eCollection 2018 Apr.
Gene duplication facilitates functional diversification and provides greater phenotypic flexibility to an organism. Expanded gene families arise through repeated gene duplication but the extent of functional divergence that accompanies each paralogous gene is generally unexplored because of the difficulty in isolating the effects of single family members. The telomere-associated (TLO) gene family is a remarkable example of gene family expansion, with 14 members in the more pathogenic Candida albicans relative to two TLO genes in the closely-related species C. dubliniensis. TLO genes encode interchangeable Med2 subunits of the major transcriptional regulatory complex Mediator. To identify biological functions associated with each C. albicans TLO, expression of individual family members was regulated using a Tet-ON system and the strains were assessed across a range of phenotypes involved in growth and virulence traits. All TLOs affected multiple phenotypes and a single phenotype was often affected by multiple TLOs, including simple phenotypes such as cell aggregation and complex phenotypes such as virulence in a Galleria mellonella model of infection. No phenotype was regulated by all TLOs, suggesting neofunctionalization or subfunctionalization of ancestral properties among different family members. Importantly, regulation of three phenotypes could be mapped to individual polymorphic sites among the TLO genes, including an indel correlated with two phenotypes, growth in sucrose and macrophage killing. Different selective pressures have operated on the TLO sequence, with the 5' conserved Med2 domain experiencing purifying selection and the gene/clade-specific 3' end undergoing extensive positive selection that may contribute to the impact of individual TLOs on phenotypic variability. Therefore, expansion of the TLO gene family has conferred unique regulatory properties to each paralog such that it influences a range of phenotypes. We posit that the genetic diversity associated with this expansion contributed to C. albicans success as a commensal and opportunistic pathogen.
基因复制为生物体提供了功能多样化和更大的表型灵活性。扩展的基因家族通过重复基因复制而产生，但由于难以隔离单个家族成员的影响，伴随每个同源基因的功能分化程度通常是未知的。端粒相关（TLO）基因家族是基因家族扩展的一个显著例子，致病性更强的白色念珠菌有 14 个 TLO 基因，而亲缘关系较近的杜波依斯念珠菌则有 2 个 TLO 基因。TLO 基因编码主要转录调控复合物 Mediator 的可互换 Med2 亚基。为了确定与每个白色念珠菌 TLO 相关的生物学功能，使用 Tet-ON 系统调控单个家族成员的表达，并在一系列与生长和毒力性状相关的表型中评估这些菌株。所有 TLO 都影响多种表型，单个表型通常受到多个 TLO 的影响，包括细胞聚集等简单表型和感染大蜡螟模型中的毒力等复杂表型。没有一个表型受到所有 TLO 的调控，这表明不同家族成员之间的祖先特性发生了新功能化或亚功能化。重要的是，三个表型的调控可以映射到 TLO 基因中的单个多态性位点，包括与两个表型（蔗糖生长和巨噬细胞杀伤）相关的插入缺失。不同的选择压力作用于 TLO 序列，5'保守的 Med2 结构域经历了纯化选择，而基因/分支特异性的 3'端则经历了广泛的正选择，这可能有助于单个 TLO 对表型变异性的影响。因此，TLO 基因家族的扩张赋予了每个同源基因独特的调控特性，从而影响了一系列表型。我们假设这种扩张所带来的遗传多样性为白色念珠菌作为共生菌和机会致病菌的成功做出了贡献。
