Multiphyletic origins of methylotrophy in Alphaproteobacteria, exemplified by comparative genomics of Lake Washington isolates.

Summary We sequenced the genomes of 19 methylotrophicisolates from Lake Washington, which belong to nine genera within eight families of the Alphaproteobacteria, two of the families being the newly proposed families. Comparative genomicanalysis with a focus on methylotrophy metabolism classifies these strains into heterotrophicand obligately or facultatively autotrophic methylotrophs. The most persistent metabolic modules enabling methylotrophy within this group are the N-methylglutamate pathway, the two types of methanol dehydrogenase(MxaFI and XoxF), the tetrahydromethanopterinpathway for formaldehyde oxidation, the serine cycle and the ethylmalonyl-CoA pathway. At the same time, a great potential for metabolic flexibility within this group is uncovered, with different combinations of these modules present. Phylogenetic analysis of key methylotrophy functions reveals that the serine cycle must have evolved independently in at least four lineages of Alphaproteobacteriaand that all methylotrophy modules seem to be prone to lateral transfers as well as deletions.