Program in Biomolecular Science and Engineering, University of California, Santa Barbara, CA, 93106, USA.
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, 93106, USA.
Nat Commun. 2022 Jun 25;13(1):3631. doi: 10.1038/s41467-022-31387-0.
Systems of catalytic RNAs presumably gave rise to important evolutionary innovations, such as the genetic code. Such systems may exhibit particular tolerance to errors (error minimization) as well as coding specificity. While often assumed to result from natural selection, error minimization may instead be an emergent by-product. In an RNA world, a system of self-aminoacylating ribozymes could enforce the mapping of amino acids to anticodons. We measured the activity of thousands of ribozyme mutants on alternative substrates (activated analogs for tryptophan, phenylalanine, leucine, isoleucine, valine, and methionine). Related ribozymes exhibited shared preferences for substrates, indicating that adoption of additional amino acids by existing ribozymes would itself lead to error minimization. Furthermore, ribozyme activity was positively correlated with specificity, indicating that selection for increased activity would also lead to increased specificity. These results demonstrate that by-products of ribozyme evolution could lead to adaptive value in specificity and error tolerance.
催化 RNA 系统可能引发了重要的进化创新,例如遗传密码。这些系统可能表现出对错误的特殊容忍度(最小化错误)和编码特异性。虽然通常假定是自然选择的结果,但最小化错误可能是一个新兴的副产品。在 RNA 世界中,自我氨酰化核酶系统可以强制将氨基酸映射到反密码子上。我们在替代底物(色氨酸、苯丙氨酸、亮氨酸、异亮氨酸、缬氨酸和蛋氨酸的活化类似物)上测量了数千个核酶突变体的活性。相关核酶对底物表现出共同的偏好,这表明现有核酶对额外氨基酸的采用本身就会导致最小化错误。此外,核酶活性与特异性呈正相关,这表明对活性增加的选择也会导致特异性增加。这些结果表明,核酶进化的副产品可能会导致特异性和容错性的适应性价值。