Origins Institute and Dept of Biology, McMaster University, Hamilton, Ontario, Canada.
Origins Institute and Dept of Physics and Astronomy, McMaster University, Hamilton, Ontario, Canada.
PLoS Comput Biol. 2022 Aug 24;18(8):e1010458. doi: 10.1371/journal.pcbi.1010458. eCollection 2022 Aug.
We present simulations of non-enzymatic template-directed RNA synthesis that incorporate primer extension, ligation, melting, and reannealing. Strand growth occurs over multiple heating/cooling cycles, producing strands of several hundred nucleotides in length, starting with random oligomers of 4 to 10 nucleotides. A strand typically grows by only 1 or 2 nucleotides in each cycle. Therefore, a strand is copied from many different templates, not from one specific complementary strand. A diverse sequence mixture is produced, and there is no exact copying of sequences, even if single base additions are fully accurate (no mutational errors). It has been proposed that RNA systems may contain a virtual circular genome, in which sequences partially overlap in a way that is mutually catalytic. We show that virtual circles do not emerge naturally in our simulations, and that a system initiated with a virtual circle can only maintain itself if there are no mutational errors and there is no input of new sequences formed by random polymerization. Furthermore, if a virtual sequence and its complement contain repeated short words, new sequences can be produced that were not on the original virtual circle. Therefore the virtual circle sequence cannot maintain itself. Functional sequences with secondary structures contain complementary words on opposite sides of stem regions. Both these words are repeated in the complementary sequence; hence, functional sequences cannot be encoded on a virtual circle. Additionally, we consider sequence replication in populations of protocells. We suppose that functional ribozymes benefit the cell which contains them. Nevertheless, scrambling of sequences occurs, and the functional sequence is not maintained, even when under positive selection.
我们展示了非酶模板指导的 RNA 合成模拟,其中包括引物延伸、连接、熔化和重新退火。链的生长发生在多个加热/冷却循环中,从 4 到 10 个核苷酸的随机寡核苷酸开始,产生数百个核苷酸长的链。在每个循环中,链通常只增长 1 或 2 个核苷酸。因此,一条链是从许多不同的模板复制而来的,而不是从一条特定的互补链复制而来的。产生了多样化的序列混合物,并且即使单个碱基的添加是完全准确的(没有突变错误),也没有对序列进行精确的复制。有人提出,RNA 系统可能包含一个虚拟的环状基因组,其中序列以相互催化的方式部分重叠。我们表明,在我们的模拟中,虚拟环不会自然出现,如果没有突变错误,并且没有通过随机聚合形成的新序列的输入,那么从虚拟环开始的系统只能维持自身。此外,如果虚拟序列及其互补序列包含重复的短词,则可以产生不在原始虚拟环上的新序列。因此,虚拟环序列无法维持自身。具有二级结构的功能序列在茎区的相对侧包含互补的词。这些词在互补序列中都被重复;因此,功能序列不能编码在虚拟环上。此外,我们还考虑了原细胞群体中的序列复制。我们假设功能核酶对包含它们的细胞有益。然而,即使在正选择下,序列也会发生混淆,并且功能序列也不会得到维持。