Brookhaven National Laboratory, Biology Department, Upton, NY.
Mol Biol Evol. 2021 Jan 23;38(2):650-662. doi: 10.1093/molbev/msaa221.
Diverging from the classic paradigm of random gene order in eukaryotes, gene proximity can be leveraged to systematically identify functionally related gene neighborhoods in eukaryotes, utilizing techniques pioneered in bacteria. Current methods of identifying gene neighborhoods typically rely on sequence similarity to characterized gene products. However, this approach is not robust for nonmodel organisms like algae, which are evolutionarily distant from well-characterized model organisms. Here, we utilize a comparative genomic approach to identify evolutionarily conserved proximal orthologous gene pairs conserved across at least two taxonomic classes of green algae. A total of 317 gene neighborhoods were identified. In some cases, gene proximity appears to have been conserved since before the streptophyte-chlorophyte split, 1,000 Ma. Using functional inferences derived from reconstructed evolutionary relationships, we identified several novel functional clusters. A putative mycosporine-like amino acid, "sunscreen," neighborhood contains genes similar to either vertebrate or cyanobacterial pathways, suggesting a novel mosaic biosynthetic pathway in green algae. One of two putative arsenic-detoxification neighborhoods includes an organoarsenical transporter (ArsJ), a glyceraldehyde 3-phosphate dehydrogenase-like gene, homologs of which are involved in arsenic detoxification in bacteria, and a novel algal-specific phosphoglycerate kinase-like gene. Mutants of the ArsJ-like transporter and phosphoglycerate kinase-like genes in Chlamydomonas reinhardtii were found to be sensitive to arsenate, providing experimental support for the role of these identified neighbors in resistance to arsenate. Potential evolutionary origins of neighborhoods are discussed, and updated annotations for formerly poorly annotated genes are presented, highlighting the potential of this strategy for functional annotation.
与真核生物中经典的随机基因顺序模式不同，基因邻近性可以被利用来系统地识别真核生物中功能相关的基因邻域，利用在细菌中开创的技术。目前识别基因邻域的方法通常依赖于与已描述的基因产物的序列相似性。然而，对于藻类等非模式生物来说，这种方法并不稳健，因为藻类与经过充分描述的模式生物在进化上相距甚远。在这里，我们利用比较基因组学的方法来识别至少跨越两个绿藻分类类别的进化保守的近端直系同源基因对。总共鉴定出 317 个基因邻域。在某些情况下，基因邻近性似乎自 10 亿年前的绿藻-红藻分裂之前就已经被保守下来。利用从重建的进化关系中得出的功能推断，我们鉴定了几个新的功能簇。一个假定的肌醇六磷酸类似氨基酸，“防晒霜”，邻域包含与脊椎动物或蓝细菌途径相似的基因，这表明绿藻中存在一种新的镶嵌生物合成途径。两个假定的砷解毒邻域之一包含一种有机砷转运蛋白（ArsJ）、一种甘油醛 3-磷酸脱氢酶样基因，该基因的同源物参与细菌中的砷解毒，以及一种新的藻类特异性磷酸甘油酸激酶样基因。在莱茵衣藻中，ArsJ 样转运蛋白和磷酸甘油酸激酶样基因的突变体对砷酸盐敏感，为这些鉴定出的邻居在抵抗砷酸盐方面的作用提供了实验支持。讨论了邻域的潜在进化起源，并提出了以前注释较差的基因的更新注释，突出了这种策略在功能注释方面的潜力。
