Journal of Molecular Evolution

, Volume 75, Issue 1–2, pp 73–78 | Cite as

INSL4 Pseudogenes Help Define the Relaxin Family Repertoire in the Common Ancestor of Placental Mammals

  • José Ignacio Arroyo
  • Federico G. Hoffmann
  • Sara Good
  • Juan C. Opazo


The relaxin/insulin-like (RLN/INSL) gene family comprises a group of signaling molecules that perform physiological roles related mostly to reproduction and neuroendocrine regulation. They are found on three different locations in the mammalian genome, which have been called relaxin family locus (RFL) A, B, and C. Early in placental mammalian evolution, the ancestral proto-RLN gene at the RFLB locus underwent successive rounds of small-scale duplications resulting in variable number of paralogous genes in different placental lineages. Most placental mammals harbor copies of the RLN2 and INSL6 paralogs in the RFLB. However, the origin of an additional paralog, INSL4 (also known as placentin), has been controversial as its phyletic distribution does not converge with its phylogenetic position. In principle, by searching for INSL4 genes in representative species of all major groups of mammals we can gain insights into when the gene originated and better reconstruct its evolutionary history. Here we identified INSL4 pseudogenes in two laurasiatherian, (alpaca and dolphin) and one xenarthran (armadillo) species. Phylogenetic and synteny analyses confirmed that the identified pseudogenes are orthologs of INSL4. According to these results, the proto-RLN gene in the RFLB underwent two successive tandem duplications which gave rise the INSL6 and INSL4 paralogs in the last common ancestor of placental mammals. The INSL4 gene was subsequently inactivated or lost from the genome in all placentals other than catarrhine primates, where its product became functionally relevant. Our results highlight the contribution of relatively old gene duplicates to the gene complement of extant species.


INSL4 Placentin Differential retention Gene family evolution Mammals Gene duplication 



We thank Sergey Yegorov for comments on the manuscript. This study was funded by Grants to JCO from the Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT 11080181). FGH acknowledges grant support from the National Science Foundation (EPS-0903787).

Supplementary material

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Supplementary material 1 (PDF 27 kb)
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Supplementary material 2 (PDF 54 kb)
239_2012_9517_MOESM3_ESM.pdf (75 kb)
Supplementary material 3 (PDF 75 kb)


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • José Ignacio Arroyo
    • 1
  • Federico G. Hoffmann
    • 2
    • 3
  • Sara Good
    • 4
  • Juan C. Opazo
    • 1
  1. 1.Instituto de Ciencias Ambientales y Evolutivas, Facultad de CienciasUniversidad Austral de ChileValdiviaChile
  2. 2.Department of Biochemistry, Molecular Biology, Entomology and Plant PathologyMississippi State UniversityStarkvilleUSA
  3. 3.Institute for Genomics, Biocomputing and BiotechnologyMississippi State UniversityStarkvilleUSA
  4. 4.Department of BiologyUniversity of WinnipegWinnipegCanada

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