Pseudogenization of the tumor-growth promoter angiogenin in a leaf-eating monkey.
Physiological functions of human genes may be studied by gene-knockout experiments in model organisms such as the mouse. This strategy relies on the existence of one-to-one gene orthology between the human and mouse. When lineage-specific gene duplication occurs and paralogous genes share a certain degree of functional redundancy, knockout mice may not provide accurate functional information on human genes. Angiogenin is a small protein that stimulates blood-vessel growth and promotes tumor development. Humans and related primates only have one angiogenin gene, while mice have three paralogous genes. This makes it difficult to generate angiogenin-knockout mice and even more difficult to interpret the genotype-phenotype relation from such animals should they be generated. We here show that in the douc langur (Pygathrix nemaeus), an Asian leaf-eating colobine monkey, the single-copy angiogenin gene has a one-nucleotide deletion in the sixth codon of the mature peptide, generating a premature stop codon. This nucleotide deletion is found in five unrelated individuals sequenced, and therefore is likely to have been fixed in the species. Five colobine species that are closely related to the douc langur have intact angiogenin genes, suggesting that the pseudogenization event was recent and unique to the douc langur lineage. This natural knockout experiment suggests that primate angiogenin is dispensable even in the wild. Further physiological studies of douc langurs may offer additional information on the role of this cancer-related gene in normal physiology of primates, including humans. Our findings also provide a strong case for the importance of evolutionary analysis in biomedical studies of gene functions.
Zhang
Jianzhi
J
Department of Ecology and Evolutionary Biology, University of Michigan, 3003 Natural Sciences Building, 830 North University Avenue, Ann Arbor, MI 48109, USA. jianzhi@umich.edu
Zhang
Ya-ping
YP
D000595:Amino Acid Sequence; D043925:Angiogenesis Inducing Agents / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D016673:Colobinae / Q000145:classification / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D014644:Genetic Variation; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics; D010802:Phylogeny; D011544:Pseudogenes / Q000235:genetics*; D012259:Ribonuclease, Pancreatic / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity
D043925:Angiogenesis Inducing Agents; D009363:Neoplasm Proteins; D004247:DNA; C046366:angiogenin; D012259:Ribonuclease, Pancreatic