ABSTRACT
Large-bodied organisms have more cells that can potentially turn cancerous than small-bodied organisms, imposing an increased risk of developing cancer. This expectation predicts a positive correlation between body size and cancer risk; however, there is no correlation between body size and cancer risk across species ("Peto's paradox"). Here, we show that elephants and their extinct relatives (proboscideans) may have resolved Peto's paradox in part through refunctionalizing a leukemia inhibitory factor pseudogene (LIF6) with pro-apoptotic functions. LIF6 is transcriptionally upregulated by TP53 in response to DNA damage and translocates to the mitochondria where it induces apoptosis. Phylogenetic analyses of living and extinct proboscidean LIF6 genes indicates that its TP53 response element evolved coincident with the evolution of large body sizes in the proboscidean stem lineage. These results suggest that refunctionalizing of a pro-apoptotic LIF pseudogene may have been permissive (although not sufficient) for the evolution of large body sizes in proboscideans.
Subject(s)
Elephants/genetics , Gene Dosage , Receptors, OSM-LIF/genetics , Tumor Suppressor Protein p53/genetics , bcl-2 Homologous Antagonist-Killer Protein/genetics , bcl-2-Associated X Protein/genetics , Animals , Apoptosis/genetics , Biological Evolution , Body Size , DNA Damage , Elephants/metabolism , Gene Duplication , Gene Expression Regulation , Humans , Mitochondria/genetics , Mitochondria/metabolism , Neoplasms/prevention & control , Phylogeny , Proboscidea Mammal/classification , Proboscidea Mammal/genetics , Protein Isoforms/genetics , Protein Isoforms/metabolism , Pseudogenes , Receptors, OSM-LIF/metabolism , Response Elements , Transcription, Genetic , Tumor Suppressor Protein p53/metabolism , bcl-2 Homologous Antagonist-Killer Protein/metabolism , bcl-2-Associated X Protein/metabolismABSTRACT
The data on an isolated upper tooth (P4) of Deinotherium sp. from the Late Miocene beds of the Maikop 1 locality (Maikop, Republic of Adygea) are reported. This is the first record of Deinotherium from the Upper Miocene of Russia. The tooth crown of P4 is similar in size to D. proavum Eichwald, 1831 (= D. gigantissimum Stefanescu, 1892).
Subject(s)
Fossils/anatomy & histology , Proboscidea Mammal/anatomy & histology , Animals , Ecosystem , Phylogeography , Proboscidea Mammal/genetics , RussiaABSTRACT
Afrotheria is the clade of placental mammals that, together with Xenarthra, Euarchontoglires and Laurasiatheria, represents 1 of the 4 main recognized supraordinal eutherian clades. It reunites 6 orders of African origin: Proboscidea, Sirenia, Hyracoidea, Macroscelidea, Afrosoricida and Tubulidentata. The apparently unlikely relationship among such disparate morphological taxa and their possible basal position at the base of the eutherian phylogenetic tree led to a great deal of attention and research on the group. The use of biomolecular data was pivotal in Afrotheria studies, as they were the basis for the recognition of this clade. Although morphological evidence is still scarce, a plethora of molecular data firmly attests to the phylogenetic relationship among these mammals of African origin. Modern cytogenetic techniques also gave a significant contribution to the study of Afrotheria, revealing chromosome signatures for the group as a whole, as well as for some of its internal relationships. The associations of human chromosomes HSA1/19 and 5/21 were found to be chromosome signatures for the group and provided further support for Afrotheria. Additional chromosome synapomorphies were also identified linking elephants and manatees in Tethytheria (the associations HSA2/3, 3/13, 8/22, 18/19 and the lack of HSA4/8) and elephant shrews with the aardvark (HSA2/8, 3/20 and 10/17). Herein, we review the current knowledge on Afrotheria chromosomes and genome evolution. The already available data on the group suggests that further work on this apparently bizarre assemblage of mammals will provide important data to a better understanding on mammalian genome evolution.
