Evolutionary dynamics of the interferon-induced transmembrane gene family in vertebrates

PLoS One. 2012;7(11):e49265. doi: 10.1371/journal.pone.0049265. Epub 2012 Nov 15.


Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated to have extensive and diverse functions, playing important roles in the evolution of vertebrates. Despite observance of their functionality, the evolutionary dynamics of this gene family are complex and currently unknown. Here, we performed detailed evolutionary analyses to unravel the evolutionary history of the vertebrate IFITM family. A total of 174 IFITM orthologous genes and 112 pseudogenes were identified from 27 vertebrate genome sequences. The vertebrate IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and IFITM10 sub-families in phylogeny, implying origins from three different progenitors. In general, vertebrate IFITM genes are located in two loci, one containing the IFITM10 gene, and the other locus containing IFITM5 and various numbers of IR-IFITM genes. Conservation of evolutionary synteny was observed in these IFITM genes. Significant functional divergence was detected among the three IFITM sub-families. No gene duplication or positive selection was found in IFITM5 sub-family, implying the functional conservation of IFITM5 in vertebrate evolution, which is involved in bone formation. No IFITM5 locus was identified in the marmoset genome, suggesting a potential association with the tiny size of this monkey. The IFITM10 sub-family was divided into two groups: aquatic and terrestrial types. Functional divergence was detected between the two groups, and five IFITM10-like genes from frog were dispersed into the two groups. Both gene duplication and positive selection were observed in aquatic vertebrate IFITM10-like genes, indicating that IFITM10 might be associated with the adaptation to aquatic environments. A large number of lineage- and species-specific gene duplications were observed in IR-IFITM sub-family and positive selection was detected in IR-IFITM of primates and rodents. Because primates have experienced a long history of viral infection, such rapid expansion and positive selection suggests that the evolution of primate IR-IFITM genes is associated with broad-spectrum antiviral activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Differentiation / genetics*
  • Base Sequence
  • Bayes Theorem
  • Chromosome Mapping
  • Evolution, Molecular*
  • Gene Duplication / genetics
  • Models, Genetic
  • Molecular Sequence Data
  • Multigene Family / genetics*
  • Phylogeny*
  • Selection, Genetic*
  • Species Specificity
  • Synteny / genetics
  • Vertebrates / genetics*


  • Antigens, Differentiation
  • leu-13 antigen

Grants and funding

This work was supported by the Open Project of State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, CAS (GREKF10-08), the “Top-notch personnel” Project of Jiangsu University to CZ, and a grant from National Natural Science Foundation of China (No. 30900793) to HY. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.