The genetic repertoire of deep-sea microbiome: From sequence to structure and function

The deep sea, as the largest and maybe most hostile environment on Earth, is still underexplored, especially regarding its genetic repertoire. Yet, previous work has revealed significant habitat-specific deep-sea biodiversity. Here, we present an integrated deep-sea microbial genetic dataset comprising 502 million nonredundant genes from 2,138 samples and 2.4 million predicted structures and use it to link specific protein structures with genetic variants associated with life in the deep sea and to assess their biotechnology potential. Combining global sequence analysis with biophysical and biochemical measurements revealed unprecedented sequence diversity and substantial structural conservation of proteins. Especially, proteins involved in replication, recombination, and repair were identified as being under rapid evolution and with specialized properties. Among these, a structurally divergent helicase exhibited advantages in controlling nanopore sequencing speed. Thus, our work positions the deep sea as an evolutionary engine that generates and hosts genetic diversity and bridges genetic knowledge with biotechnology.