Cross-feeding supports the growth of ammonia-oxidizing bacteria with reduced genomes during evolution

Bacteria usually lose redundant genes to reduce genome sizes during evolution to achieve high metabolic efficiency. Here, we combined molecular clock with flux balance analysis to propose that ammonia-oxidizing bacteria (AOB), which are crucial for the global nitrogen cycle, have lost genes involved in essential metabolite biosynthesis during genome reduction and consequently rely on metabolic cross-feeding. A newly evolved ammonia-oxidizing bacteria originating in the Phanerozoic time with a genome size of 2.17 Mb lost genes necessary for synthetizing amino acids (asparagine and methionine, etc.), from the older AOB species originating in the Proterozoic time with genome sizes of 4.53 Mb. Symbiotic bacteria supplied these essential amino acids and dipeptides to newly evolved AOB to support their growth. Meanwhile, AOB degraded the absorbed dipeptides into amino acids or synthesized dipeptides from absorbed amino acids to trade with the symbiotic bacteria, establishing a strong mutually supportive relationship. Newly evolved AOB with reduced genomes in the Yangtze River absorb amino acids and dipeptides from other bacteria, resulting in a growth rate increase of 172.8% compared to those old AOB. This study hints the microbial division of labor becomes refined to improve metabolic efficiency during evolution and the roles of cross feedings in driving gene reduction.