It is likely that RNA replication began non-enzymatically, and that polymerases were later selected to speed up the process. We consider replication mechanisms in modern viruses and ask which of these is possible non-enzymatically, using mathematical models and experimental data found in the literature to estimate rates of RNA synthesis and replication. Replication via alternating plus and minus strands is found in some single-stranded RNA viruses. However, if this occurred non-enzymatically it would lead to double-stranded RNA that would not separate. With some form of environmental cycling, such as temperature, salinity, or pH cycling, double-stranded RNA can be melted to form single-stranded RNA, although re-annealing of existing strands would then occur much faster than synthesis of new strands. We show that re-annealing blocks this form of replication at a very low concentration of strands. Other kinds of viruses synthesize linear double strands from single strands and then make new single strands from double strands via strand-displacement. This does not require environmental cycling and is not blocked by re-annealing. However, under non-enzymatic conditions, if strand-displacement occurs from a linear template, we expect the incomplete new strand to be almost always displaced by the tail end of the old strand through toehold-mediated displacement. A third kind of replication in viruses and viroids is rolling-circle replication which occurs via strand-displacement on a circular template. Rolling-circle replication does not require environmental cycling and is not prevented by toehold-mediated displacement. Rolling-circle replication is therefore expected to occur non-enzymatically and is a likely starting point for the evolution of polymerase-catalysed replication.

RNA复制很可能以非酶促方式开始，后来选择聚合酶来加速这一过程。我们考虑了现代病毒中的复制机制，并使用数学模型和文献中的实验数据来估计 RNA 合成和复制的速率，并询问其中哪些可能是非酶促的。在一些单链 RNA 病毒中发现通过交替的正负链进行复制。然而，如果这在非酶促作用下发生，则会导致无法分离的双链 RNA。通过某种形式的环境循环，例如温度、盐度或 pH 值循环，双链 RNA 可以熔化形成单链 RNA，尽管现有链的重新退火会比新链的合成快得多。我们表明，在非常低的链浓度下，重新退火会阻止这种形式的复制。其他种类的病毒从单链合成线性双链，然后通过链置换从双链合成新的单链。这不需要环境循环并且不会被重新退火阻止。然而，在非酶促条件下，如果从线性模板发生链置换，我们预计不完整的新链几乎总是通过立足点介导的置换被旧链的尾端置换。病毒和类病毒中的第三种复制是滚环复制，它通过环状模板上的链置换发生。滚环复制不需要环境循环，也不会被立足点介导的置换阻止。