ABSTRACT
While most mammals including the prosimians have a single copy of the growth hormone (GH) gene, anthropoids possess a cluster of GH-related genes. Throughout the evolution of the main anthropoid groups [New World Monkeys (NWM), Old World Monkeys (OWM), and apes], two features stand out of the GH loci. The first is the appearance of chorionic somatommamotropin hormone (CSH) genes within the OWM lineage and the second is the expansion of the loci intergenic regions in the OWM and apes. In relation with this loci expansion, the NWM possess intergenic regions of homogeneous lengths (3.5 kb). In contrast, heterogeneous lengths (6 and 13 kb) have been reported for species of the OWM. At the present, none of the OWM genomic GH loci organizations have been described. Here, we report the genomic organization of the GH locus in the rhesus monkey, this locus has six GH-related genes separated by five intergenic regions. The 5' end gene (GH-1) encodes for the pituitary GH and is followed by CSH-1, GH-2, CSH-2, CSH-3 and CSH-4 genes. The five intergenic regions have heterogeneous lengths and also present more or less the same Alu distribution as the human GH locus. To analyze the events that contributed to the extension of the intergenic regions of the GH locus and the emergence of the regulatory elements, the five GH locus intergenic regions of the spider monkey (NWM) were sequenced. The results of comparing the loci from both species suggest that the long intergenic regions (13 kb) of the rhesus GH locus share a common ancestor with the 3.5 kb intergenic regions of the spider monkey. However, the observed increased length of the former is due to an insertion (approximately 8.7 kb) at their 3' end. Interestingly in this insert, we discovered a DNA element resembling the enhancer of the CSH genes of the human GH locus. On the other hand, we observed that the short intergenic regions (6 kb) increased by a different recombination event.
Subject(s)
Cercopithecidae/genetics , Evolution, Molecular , Growth Hormone/genetics , Platyrrhini/genetics , Alu Elements , Animals , Base Sequence , Cebidae/genetics , Cercopithecidae/classification , Cloning, Molecular , DNA/genetics , DNA Primers/genetics , DNA, Intergenic , Gene Duplication , Genes, Regulator , Humans , Macaca mulatta/genetics , Molecular Sequence Data , Multigene Family , Platyrrhini/classification , Recombination, Genetic , Sequence Homology, Nucleic Acid , Species Specificity , Time FactorsABSTRACT
Growth hormone (GH) has been previously described as showing distinct evolutionary stories between primates and other mammals. A burst of changes and successive amplification events took place in the primate lineage giving rise to a multigene family in the three Anthropoidea lineages. Polymerase chain reaction (PCR) was used to obtain the genes and the intergenic regions comprising the GH loci of the spider monkey (Ateles geoffroyi), a New-World primate, and of the chimpanzee (Pan troglodytes), an ape. The intergenic sequences of both species were screened by hybridization to detect copies of the Alu family, which have been implicated in the formation of the human GH locus. The GH locus of the spider monkey contains at least six GH-related genes, four of them were cloned. Likewise, five short intergenic sequences of approximately 3 kb were amplified and cloned. On the other hand, in the chimpanzee four new placental lactogen (PL) genes as well as four intergenic regions were amplified. Consequently, in this ape, six genes (two GHs, previously obtained, and four PLs) are clustered, separated by intergenic sequences of different lengths (two short ones of about 5 kb, and at least two long ones between 9 and 13 kb). The presence of Alu sequences within the intergenic regions of both GH loci corroborates the current hypothesis that they acted as a driving force for the locus expansion. GH sequence comparisons reveal that several gene-conversion events might have occurred during the formation of this genome region, which has undergone independent evolution in the three Anthropoidea branches. To establish the GH's evolutionary history may prove to be a difficult task due to these gene-conversion events.
Subject(s)
Cebidae/genetics , Growth Hormone/genetics , Pan troglodytes/genetics , Amino Acid Sequence , Animals , DNA/chemistry , DNA/genetics , DNA, Intergenic/genetics , Gene Conversion , Gene Duplication , Genetic Variation , Genome , Molecular Sequence Data , Phylogeny , Placental Lactogen/genetics , Polymerase Chain Reaction , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Amino AcidABSTRACT
La información genética de los organismos está almacenada en los genes como consecuencias de DNA. La expresión de estos genes se regula en varios niveles, siendo uno de los más importantes la transferencia de esta información a moléculas de RNA mensajeros. A este proceso se le llama transcripción y es catalizado por una maquinaria molecular constituida por un centenar de proteínas que se ensamblan ordenadamente. Estas proteínas o factores transcripcionales se dividen en 4 grupos según su modo de acción; a saber: generales, activadores, coactivadores y represores. Existen enfermedades en las que se ven implicados algunos de estos factores transcripcionales, habiéndose ya identificado la mutación o la falla molecular en el factor transcripcional involucrado, entre las cuales se pueden mencionar la aniridia, el síndrome de Rubinstein-Taybi y enfermedad de Hodgkin. El conocimiento a nivel molecular del proceso de transcripción ayudará a comprender mejor la relación que tiene éste con el desarrollo y la salud de los individuos, así como a encontrar nuevos tratamientos para las enfermedades
