  Prokaryote mobilome genomes rely on host machineries for survival and
replication. Given that mobile genetic elements (MGEs) derive their energy from
host cells, we investigated the diversity of ATP-utilizing proteins in MGE
genomes to determine whether they might be associated with proteins that could
suppress related host proteins that consume host energy. A comprehensive search
of 353 huge phage genomes revealed that up to 9% of the proteins have ATPase
domains. For example, ATPase proteins constitute ~3% of the genomes of Lak
phages with ~550 kbp genomes that occur in the microbiomes of humans and other
animals. Statistical analysis shows the number of ATPase proteins increases
linearly with genome length, consistent with a large sink for host ATP during
replication of megaphages. Using metagenomic data from diverse environments, we
found 505 mobilome proteins with ATPase domains fused to diverse functional
domains. Among these composite ATPase proteins, 61.6% have known functional
domains that could contribute to host energy diversion during the mobilome life
cycle. As many have domains that are known to interact with nucleic acids and
proteins, we infer that numerous ATPase proteins are used during replication
and for protection from host immune systems. We found a set of uncharacterized
ATPase proteins with nuclease and protease activities, displaying unique domain
architectures that are energy intensive based on the presence of multiple
ATPase domains. In many cases, these composite ATPase proteins genomically
co-localize with small proteins in genomic contexts that are reminiscent of
toxin-antitoxin systems. Small proteins that function as inhibitors may be a
common strategy for control of cellular processes, thus could inspire the
development of new nucleic acid and protein manipulation tools, with diverse
biotechnological applications.
