title: Evolution and divergence of the mammalian SAMD9/SAMD9L gene family.
abstract: BACKGROUND
  The physiological functions of the human Sterile Alpha Motif Domain-containing 9 (SAMD9) gene and its chromosomally adjacent paralogue, SAMD9-like (SAMD9L), currently remain unknown. However, the direct links between the deleterious mutations or deletions in these two genes and several human disorders, such as inherited inflammatory calcified tumors and acute myeloid leukemia, suggest their biological importance. SAMD9 and SAMD9L have also recently been shown to play key roles in the innate immune responses to stimuli such as viral infection. We were particularly interested in understanding the mammalian evolutionary history of these two genes. The phylogeny of SAMD9 and SAMD9L genes was reconstructed using the Maximum Likelihood method. Furthermore, six different methods were applied to detect SAMD9 and SAMD9L codons under selective pressure: the site-specific model M8 implemented in the codeml program in PAML software and five methods available on the Datamonkey web server, including the Single Likelihood Ancestor Counting method, the Fixed Effect Likelihood method, the Random Effect Likelihood method, the Mixed Effects Model of Evolution method and the Fast Unbiased Bayesian AppRoximation method. Additionally, the house mouse (Mus musculus) genome has lost the SAMD9 gene, while keeping SAMD9L intact, prompting us to investigate whether this loss is a unique event during evolution.
  
  
  RESULTS
  Our evolutionary analyses suggest that SAMD9 and SAMD9L arose through an ancestral gene duplication event after the divergence of Marsupialia from Placentalia. Additionally, selection analyses demonstrated that both genes have been subjected to positive evolutionary selection. The absence of either SAMD9 or SAMD9L genes from some mammalian species supports a partial functional redundancy between the two genes.
  
  
  CONCLUSIONS
  To the best of our knowledge, this work is the first study on the evolutionary history of mammalian SAMD9 and SAMD9L genes. We conclude that evolutionary selective pressure has acted on both of these two genes since their divergence, suggesting their importance in multiple cellular processes, such as the immune responses to viral pathogens.
authors.affiliation: Centro de Investigação em Biodiversidade e Recursos Genéticos/InBio Laboratório Associado, Universidade do Porto, 4485-661 Vairão, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Lemos de Matos
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Grant
authors.initials: G
authors.lastname: McFadden
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Esteves
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001499:Bayes Theorem; D019143:Evolution, Molecular; D020440:Gene Duplication; D016678:Genome; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008322:Mammals / Q000145:classification / Q000235:genetics*; D051379:Mice; D005810:Multigene Family; D010802:Phylogeny; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C514443:SAMD9 protein, human; D025521:Tumor Suppressor Proteins