ArticlePLoS biology2018
Loss of RXFP2 and INSL3 genes in Afrotheria shows that testicular descent is the ancestral condition in placental mammals.
Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 91 citations in OpenAlex.
- Evolutionary relaxation and functional change of INSL3 and RXFP2 may underlie natural cryptorchidism in mammals.EMBO reports · 2025Article
- Age cohort definition and evidence of sexual dimorphism in the Southern Hairy-nosed Wombat (Journal of mammalogy · 2025Article
- The fourspine stickleback (Apeltes quadracus) has an XY sex chromosome system with polymorphic inversions on both X and Y chromosomes.PLoS genetics · 2025Article
- Identification of key genes related to unilateral cryptorchidism in sheep by comprehensive transcriptomics and proteomics analyses.BMC genomics · 2025Article
- Unearthing the secrets of Australia's most enigmatic and cryptic mammal, the marsupial mole.Science advances · 2025Article
- Article
- Comparative Analyses Reveal Conserved and Modified Steps in the Testis Descent and Scrotum Development in Mouse and Opossum.Cells, tissues, organs · 2025Article
- Relaxed selection in evolution of genes regulating limb development gives clue to variation in forelimb morphology of cetaceans and other mammals.Proceedings. Biological sciences · 2024Article
- Sublethal heat reduces overall reproductive investment and male allocation in a simultaneously hermaphroditic snail species.Royal Society open science · 2024Article
- Therian origin of INSL3/RXFP2-driven testicular descent in mammals.Frontiers in cell and developmental biology · 2024Article
- The RXFP2-PLC/PKC signaling pathway mediates INSL3-induced regulation of the proliferation, migration and apoptosis of mouse gubernacular cells.Cellular & molecular biology letters · 2023Article
- GPR15-C10ORF99 functional pairing initiates colonic Treg homing in amniotes.EMBO reports · 2022Article
- Article
- Genomic and anatomical comparisons of skin support independent adaptation to life in water by cetaceans and hippos.Current biology : CB · 2021Article
- Rapid evolution and molecular convergence in cryptorchidism-related genes associated with inherently undescended testes in mammals.BMC ecology and evolution · 2021Article
- Recapitulating Evolutionary Divergence in a Single Cis-Regulatory Element Is Sufficient to Cause Expression Changes of the Lens Gene Tdrd7.Molecular biology and evolution · 2021Article
- Signatures of conserved and unique molecular features in Afrotheria.Scientific reports · 2021Article
- Article
- Diverse functions of insulin-like 3 peptide.The Journal of endocrinology · 2020Review
- PseudoChecker: an integrated online platform for gene inactivation inference.Nucleic acids research · 2020Article
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Descent of testes from a position near the kidneys into the lower abdomen or into the scrotum is an important developmental process that occurs in all placental mammals, with the exception of five afrotherian lineages. Since soft-tissue structures like testes are not preserved in the fossil record and since key parts of the placental mammal phylogeny remain controversial, it has been debated whether testicular descent is the ancestral or derived condition in placental mammals. To resolve this debate, we used genomic data of 71 mammalian species and analyzed the evolution of two key genes (relaxin/insulin-like family peptide receptor 2 [RXFP2] and insulin-like 3 [INSL3]) that induce the development of the gubernaculum, the ligament that is crucial for testicular descent. We show that both RXFP2 and INSL3 are lost or nonfunctional exclusively in four afrotherians (tenrec, cape elephant shrew, cape golden mole, and manatee) that completely lack testicular descent. The presence of remnants of once functional orthologs of both genes in these afrotherian species shows that these gene losses happened after the split from the placental mammal ancestor. These "molecular vestiges" provide strong evidence that testicular descent is the ancestral condition, irrespective of persisting phylogenetic discrepancies. Furthermore, the absence of shared gene-inactivating mutations and our estimates that the loss of RXFP2 happened at different time points strongly suggest that testicular descent was lost independently in Afrotheria. Our results provide a molecular mechanism that explains the loss of testicular descent in afrotherians and, more generally, highlight how molecular vestiges can provide insights into the evolution of soft-tissue characters.
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