Why Genes Evolve Faster on Secondary Chromosomes in Bacteria

In bacterial genomes composed of more than one chromosome, one replicon is typically larger, harbors more essential genes than the others, and is considered primary. The greater variability of secondary chromosomes among related taxa has led to the theory that they serve as an accessory genome for specific niches or conditions. By this rationale, purifying selection should be weaker on genes on secondary chromosomes because of their reduced necessity or usage. To test this hypothesis we selected bacterial genomes composed of multiple chromosomes from two genera, Burkholderia and Vibrio, and quantified the evolutionary rates (dN and dS) of all orthologs within each genus. Both evolutionary rate parameters were faster among orthologs found on secondary chromosomes than those on the primary chromosome. Further, in every bacterial genome with multiple chromosomes that we studied, genes on secondary chromosomes exhibited significantly weaker codon usage bias than those on primary chromosomes. Faster evolution and reduced codon bias could in turn result from global effects of chromosome position, as genes on secondary chromosomes experience reduced dosage and expression due to their delayed replication, or selection on specific gene attributes. These alternatives were evaluated using orthologs common to genomes with multiple chromosomes and genomes with single chromosomes. Analysis of these ortholog sets suggested that inherently fast-evolving genes tend to be sorted to secondary chromosomes when they arise; however, prolonged evolution on a secondary chromosome further accelerated substitution rates. In summary, secondary chromosomes in bacteria are evolutionary test beds where genes are weakly preserved and evolve more rapidly, likely because they are used less frequently.

在由多条染色体构成的细菌基因组中，通常存在一个更大的复制子（replicon），其所携带的必需基因数量多于其余复制子，该复制子被认定为主染色体。相关类群间的次级染色体变异程度更高，这一现象催生了相关理论：次级染色体可作为适配特定生态位或环境条件的附属基因组。据此理论，由于次级染色体上的基因必要性或使用频率更低，其受到的纯化选择强度应当弱于主染色体上的基因。为验证该假说，我们选取了伯克霍尔德氏菌属（Burkholderia）与弧菌属（Vibrio）两个类群中拥有多条染色体的细菌基因组，对每个属内所有直系同源基因（orthologs）的进化速率（dN与dS）进行了定量分析。结果显示，次级染色体上的直系同源基因的两项进化速率参数均显著快于主染色体上的基因。此外，在我们研究的所有多染色体细菌基因组中，次级染色体上的基因的密码子使用偏好性均显著弱于主染色体上的基因。进化速率更快与密码子偏好性降低，可能源于染色体位置带来的全局效应：次级染色体上的基因因复制延迟，会出现基因剂量与表达量下降的情况；或是受到特定基因属性的选择压力。我们通过对比多染色体基因组与单染色体基因组共有的直系同源基因集，对这两种可能性进行了评估。对该直系同源基因集的分析结果表明：天生进化速率更快的基因在产生时倾向于被分配至次级染色体；但在次级染色体上经历长期进化后，基因的替换速率会进一步加快。综上，细菌中的次级染色体是进化试验台：其上的基因受到的选择约束更弱，进化速率更快，这大概率源于这些基因的使用频率更低。