Summary auto-generated
This study identifies two previously unrecognized genes, RL6 and RL5A, in human cytomegalovirus (HCMV) by analyzing genome sequences from multiple viral strains. Both genes encode proteins containing the RL11D domain, establishing them as new members of the HCMV RL11 family—a multigene family of 12 genes encoding membrane glycoproteins. The researchers discovered that RL5A was missed in earlier analyses because it is disrupted by a frameshift mutation in the laboratory strain AD169, while RL6 was excluded due to being small and lacking a chimpanzee cytomegalovirus counterpart. Through Northern blotting and sequence mapping, the authors confirmed that both genes are transcribed during late infection, producing mRNAs of 0.2–0.6 kb and 3.4 kb respectively. Notably, the study reveals that a homologous domain (CR1) exists in human adenovirus E3 membrane glycoproteins, indicating evolutionary conservation of this domain across different virus families. The RL11D/CR1 domain is characterized by conserved tryptophan and cysteine residues and glycosylation sites, with extensive sequence divergence and variable gene arrangements between cytomegaloviruses and adenoviruses suggesting complex evolutionary histories involving duplication and selective sequence loss.
Key findings
- Two new HCMV genes, RL6 and RL5A, encode proteins containing the RL11D domain characteristic of the RL11 multigene family
- RL5A was previously undetected due to frameshift mutation in AD169 laboratory strain; RL6 was excluded from earlier analyses despite being transcribed during late infection
- A homologous domain (CR1) is present in human adenovirus E3 membrane proteins, indicating evolutionary relationship between cytomegalovirus and adenovirus gene families
- The conserved CR1/RL11D domain contains characteristic tryptophan and cysteine residues with potential N-linked glycosylation sites but shows high sequence variability across strains
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Abstract
A significant proportion of the human cytomegalovirus (HCMV) genome comprises 12 multigene families that probably arose by gene duplication. One, the RL11 family, contains 12 members, most of which are predicted to encode membrane glycoproteins. Comparisons of sequences near the left end of the genome in several HCMV strains revealed two adjacent open reading frames that potentially encode related proteins: RL6, which is hypervariable, and RL5A, which has not been recognized previously. These genes potentially encode a domain that is the hallmark of proteins encoded by the RL11 family, and thus constitute two new members. A homologous domain is also present in a subset of human adenovirus E3 membrane glycoproteins. Evolution of genes specifying the shared domain in cytomegaloviruses and adenoviruses is characterized by extensive divergence, gene duplication and selective sequence loss. These features prompt speculation about the roles of these genes in the two virus families.
The GenBank accession numbers of the HCMV sequences reported in this paper are AY156040AY156045.