Proteome size reduction in Apicomplexans is linked with loss of DNA repair and host redundant pathways.

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.

Synergism between the Black Queen effect and the proteomic constraint on genome size reduction in the photosynthetic picoeukaryotes.

The photosynthetic picoeukaryotes (PPEs) comprise a rare example of free-living eukaryotes that have undergone genome reduction. Here, we examine a duality in the process; the proposed driver of genome reduction (the Black Queen hypothesis, BQH), and the resultant impact of genome information loss (the Proteomic Constraint hypothesis, PCH). The BQH predicts that some metabolites may be shared in the open ocean, thus driving loss of redundant metabolic pathways in individual genomes. In contrast, the PCH predicts that as the information content of a genome is reduced, the total mutation load is also reduced, leading to loss of DNA repair genes due to the resulting reduction in selective constraint. Consistent with the BQH, we observe that biosynthetic pathways involved with soluble metabolites such as amino acids and carotenoids are preferentially lost from the PPEs, in contrast to biosynthetic pathways involved with insoluble metabolites, such as lipids, which are retained. Consistent with the PCH, a correlation between proteome size and the number of DNA repair genes, and numerous other informational categories, is observed. While elevated mutation rates resulting from the loss of DNA repair genes have been linked to reduced effective population sizes in intracellular bacteria, this remains to be established. This study shows that in microbial species with large population sizes, an underlying factor in modulating their DNA repair capacity appears to be information content.

The distribution of recombination repair genes is linked to information content in bacteria.

The concept of a 'proteomic constraint' proposes that the information content of the proteome exerts a selective pressure to reduce mutation rates, implying that larger proteomes produce a greater selective pressure to evolve or maintain DNA repair, resulting in a decrease in mutational load. Here, the distribution of 21 recombination repair genes was characterized across 900 bacterial genomes. Consistent with prediction, the presence of 17 genes correlated with proteome size. Intracellular bacteria were marked by a pervasive absence of recombination repair genes, consistent with their small proteome sizes, but also consistent with alternative explanations that reduced effective population size or lack of recombination may decrease selection pressure. However, when only non-intracellular bacteria were examined, the relationship between proteome size and gene presence was maintained. In addition, the more widely distributed (i.e. conserved) a gene, the smaller the average size of the proteomes from which it was absent. Together, these observations are consistent with the operation of a proteomic constraint on DNA repair. Lastly, a correlation between gene absence and genome AT content was shown, indicating a link between absence of DNA repair and elevated genome AT content.