Genome reduction occurred in early Prochlorococcus with an unusually low effective population size

In the oligotrophic sunlit ocean, the most abundant free-living planktonic bacterial lineages evolve convergently through genome reduction. The cyanobacterium Prochlorococcus responsible for 10% global oxygen production is a prominent example. The dominant theory known as ‘genome streamlining’ posits that they have extremely large effective population sizes ( N e ) such that selection for metabolic efficiency acts to drive genome reduction. Because genome reduction largely took place anciently, this theory builds on the assumption that their ancestors’ N e was similarly large. Constraining N e for ancient ancestors is challenging because experimental measurements of extinct organisms are impossible and alternatively reconstructing ancestral N e with phylogenetic models gives large uncertainties. Here, we develop a new strategy that leverages agent-based modeling to simulate the change of N e proxy for ancient ancestors, the genome-wide ratio of radical to conservative nonsynonymous nucleotide substitution rate (d R /d C ), in response to the change of N e . Surprisingly, this proxy shows expected increases with decreases of N e only when N e falls to about 10k – 100k or lower, magnitudes characteristic of N e of obligate endosymbiont species where drift drives genome reduction. We therefore conclude that drift, rather than selection, is the primary force that drove Prochlorococcus genome reduction. ### Competing Interest Statement The authors have declared no competing interest.