Strong genome-wide selection early in the evolution of Prochlorococcus resulted in a reduced genome through the loss of a large number of small effect genes.

The smallest genomes of any photosynthetic organisms are found in a group of free-living marine cyanobacteria, Prochlorococcus. To determine the underlying evolutionary mechanisms, we developed a new method to reconstruct the steps leading to the Prochlorococcus genome reduction using 12 Prochlorococcus and 6 marine Synechococcus genomes. Our results reveal that small genome sizes within Prochlorococcus were largely determined shortly after the split of Prochlorococcus and Synechococcus (an early big shrink) and thus for the first time decouple the genome reduction from Prochlorococcus diversification. A maximum likelihood approach was then used to estimate changes of nucleotide substitution rate and selection strength along Prochlorococcus evolution in a phylogenetic framework. Strong genome wide purifying selection was associated with the loss of many genes in the early evolutionary stage. The deleted genes were distributed around the genome, participated in many different functional categories and in general had been under relaxed selection pressure. We propose that shortly after Prochlorococcus diverged from its common ancestor with marine Synechococcus, its population size increased quickly thus increasing efficacy of selection. Due to limited nutrients and a relatively constant environment, selection favored a streamlined genome for maximum economy. Strong genome wide selection subsequently caused the loss of genes with small functional effect including the loss of some DNA repair genes. In summary, genome reduction in Prochlorococcus resulted in genome features that are similar to symbiotic bacteria and pathogens, however, the small genome sizes resulted from an increase in genome wide selection rather than a consequence of a reduced ecological niche or relaxed selection due to genetic drift.