Hypervariable Proteins in Microbes

Abstract

Numerous proteins involved in essential cellular functions are highly conserved in evolution. On the opposite end of the evolutionary spectrum are proteins that function in defensive and “offensive” roles. These proteins evolve extremely fast, often under the pressure of positive selection, producing enormous diversity. We investigated in detail different classes of hypervariable proteins in archaea and bacteria including anti-CRISPR proteins, polymorphic toxins and antitoxin immunity proteins. Using dedicated computational pipelines and machine learning methods, we predicted thousands of proteins in each of these functional groups that are encoded in a broad diversity of bacteria and archaea as well as viruses and integrated elements. Most of these proteins have not been studied experimentally and are currently unannotated or misannotated in genomic sequences. These hypervariable proteins were classified into families using sensitive methods for sequence analysis, their evolutionary relationships were investigated and specific functions predicted wherever possible.