TABLE 3.

Summary of mutations^a present in viruses selected for reverse engineering compared to the SLS progenitor

Virus (yr isolated; virulence grade)	No. of synonymous substitutions	No. of nonsynonymous substitutions	Indels in ORFs	No. of intergenic indelsh	No. of intergenic substitutions
Ur (1953; 5b)	3	5	M005L/R,c M014L, M134Rd	2	0
Meby (1991; 3/4)	24	35	M009L,e M083L,f M134R, M153R	3	1
SWH 8/2/93 (1993; 2)	21	40	M009L, M083L, M134R	10	1
OB3 Y317 (1994; 5)	24	42	M009L, M012L, M021L,g M018L, M064R, M083L, M134R, M156R	9	1

^aMutations in TIRs were counted only once.

^bUr was originally defined as the prototype grade 4 virulence virus (18), but in our hands, it has consistently been a grade 5 virus causing severe clinical myxomatosis but a very low CFR.

^cGenes in boldface type were replaced in reverse-engineered viruses and are described in Table 1. Underlined genes have the reading frame disrupted.

^dUr has a single A insert toward the 3′ end of M134L. This disrupts the ORF and leads to a protein that retains a predicted C-terminal transmembrane domain but is 27 aa shorter than the 2,000-aa SLS protein. All the other viruses have a 3A insert at this point, which maintains the ORF.

^eM009L is disrupted in all but one Australian virus isolate made after 1990; M009 is predicted to be an E3 ubiquitin ligase.

^fThe insertion in M083L repairs a disrupted ORF found in SLS and early-derived viruses such as Ur.

^gInsertions in M021L and M064R do not disrupt the ORF. The insertion in M018L alters the sequence after aa 60 and reads through to add an extra 20 aa to the normal 66-aa sequence. The function of this protein is not known. The indel in M156R is at the 3′ end of the gene and leads to a readthrough with the addition of 2 aa at the C terminus of the protein. M156 is an eIF2α homologue that inhibits protein kinase R.

^hIntergenic indels range in size from 1 to 32 nt.