Environmental Sciences Department, University of Puerto Rico-Rio Piedras, United States of America.
Biology Department, University of Puerto Rico-Rio Piedras, United States of America.
Infect Genet Evol. 2021 Jan;87:104642. doi: 10.1016/j.meegid.2020.104642. Epub 2020 Dec 6.
Apicomplexans are alveolate parasites which include Plasmodium falciparum, the main cause of malaria, one of the world's biggest killers from infectious disease. Apicomplexans are characterized by a reduction in proteome size, which appears to result from metabolic and functional simplification, commensurate with their parasitic lifestyle. However, other factors may also help to explain gene loss such as population bottlenecks experienced during transmission, and the effect of reducing the overall genomic information content. The latter constitutes an 'informational constraint', which is proposed to exert a selective pressure to evolve and maintain genes involved in informational fidelity and error correction, proportional to the quantity of information in the genome (which approximates to proteome size). The dynamics of gene loss was examined in 41 Apicomplexan genomes using orthogroup analysis. We show that loss of genes involved in amino acid metabolism and steroid biosynthesis can be explained by metabolic redundancy with the host. We also show that there is a marked tendency to lose DNA repair genes as proteome size is reduced. This may be explained by a reduction in size of the informational constraint and can help to explain elevated mutation rates in pathogens with reduced genome size. Multiple Sequentially Markovian Coalescent (MSMC) analysis indicates a recent bottleneck, consistent with predictions generated using allele-based population genetics approaches, implying that relaxed selection pressure due to reduced population size might have contributed to gene loss. However, the non-randomness of pathways that are lost challenges this scenario. Lastly, we identify unique orthogroups in malaria-causing Plasmodium species that infect humans, with a high proportion of membrane associated proteins. Thus, orthogroup analysis appears useful for identifying novel candidate pathogenic factors in parasites, when there is a wide sample of genomes available.
顶复动物门是一类有囊泡的寄生虫，包括恶性疟原虫，它是疟疾的主要病原体，也是由传染病引起的世界上最大的杀手之一。顶复动物门的蛋白质组大小减小，这似乎是由于代谢和功能简化所致，与它们的寄生生活方式相一致。然而，其他因素也可能有助于解释基因的丢失，例如在传播过程中经历的种群瓶颈，以及降低整体基因组信息含量的影响。后者构成了一种“信息约束”，据推测，它对进化和维持与信息保真和纠错相关的基因施加了选择性压力，与基因组中的信息量成正比（大致相当于蛋白质组的大小）。通过正交群分析，在 41 种顶复动物门基因组中研究了基因丢失的动态。我们表明，参与氨基酸代谢和类固醇生物合成的基因的丢失可以用与宿主的代谢冗余来解释。我们还表明，随着蛋白质组大小的减小，DNA 修复基因明显有丢失的趋势。这可以用信息约束的大小减小来解释，并且可以帮助解释具有较小基因组的病原体中升高的突变率。多重序列马尔可夫凝聚（MSMC）分析表明存在近期瓶颈，这与基于等位基因的群体遗传学方法生成的预测一致，这意味着由于种群规模减小而导致的选择压力降低可能导致了基因丢失。然而，丢失的途径的非随机性挑战了这种情况。最后，我们在感染人类的引起疟疾的疟原虫物种中识别出独特的正交群，其中很大一部分与膜相关蛋白有关。因此，当有广泛的基因组样本可用时，正交群分析似乎可用于鉴定寄生虫中的新型候选致病因子。
