DNA Modification and Restriction: Selfish Behavior of an Epigenetic System

Abstract

Type II restriction endonucleases (R) are known to make double-strand breaks within or near specific recognition sequences on duplex DNA. Cognate modification enzymes (M) can methylate these sequences and protect them from cleavage (Wilson and Murray 1991). The tight association of a cognate restriction enzyme gene with a modification gene has been termed the (type II) restriction-modification (RM) system.

Although the RM systems that have been described are individually highly specific for one or a few recognition sequences, collectively the sequences recognized are quite diverse. Type II RM systems are ubiquitous in prokaryotes and in archaebacteria but are absent from eukaryotes (Wilson and Murray 1991).

Type II restriction enzymes cleave foreign DNA such as viral and plasmid DNA when this DNA has not been modified by the appropriate modification enzyme. In this way, cells are protected from invasion by foreign DNA. Thus, it has been widely believed that the evolution and maintenance of type II restriction modification systems have been driven by the cell’s need to protect itself from infection by foreign DNA (the cellular defense hypothesis). However, there are several unresolved issues that cannot be explained satisfactorily by this cellular defense hypothesis. Here, I present experimental evidence and theoretical arguments for an alternative hypothesis (the selfish gene hypothesis) that the evolution of at least some RM gene pairs is driven by their “selfishness” in the genetic and evolutionary sense of the term.

WEAK POINTS OF THE CELLULAR DEFENSE HYPOTHESIS
The phenomena associated with type II RM systems that have...