Alu-mediated phylogenetic novelties in gene regulation and development.
Differential gene expression lies at the heart of biology and is responsible for all developmental processes, including the growth and differentiation of cells. Perhaps even speciation could be defined as a change in differential gene expression over evolutionary time. The present work is a phylogenetic study of four Alu elements known to have gene regulatory functions in the human. The four elements have been shown to regulate the parathyroid hormone (PTH) gene via a negative calcium-response element, the hematopoietic cell-specific FcepsilonRI-gamma receptor gene via a cis-acting positive/negative regulatory element, the CNS-specific nicotinic acetylcholine receptor alpha3 gene via a cis-acting positive/negative control element, and the T-cell-specific CD8alpha gene via a complex transcriptional regulator. The four Alu elements that impact differential gene expression were found to be differentially distributed among seven primate species (human, chimpanzee, gorilla, orangutan, baboon, rhesus, and macaque) in a way that is congruent with an accepted phylogeny of these species. The results establish a link between gene regulation and the divergence of primates. This evolutionary variation in gene regulation also suggests a novel experimental system to study the very complex transcriptional regulation of gene expression, by studying side-by-side the regulation of the same gene from two primate species that differ in the cis-acting regulatory elements of the gene.
Hamdi
H K
HK
Department of Biochemistry, University of California, Riverside, CA, 92521, USA.
Nishio
H
H
Tavis
J
J
Zielinski
R
R
Dugaiczyk
A
A
D020087:Alu Elements / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D016827:CD8 Antigens / Q000235:genetics; D002118:Calcium / Q000494:pharmacology; D002520:Cercopithecidae / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics; D019143:Evolution, Molecular; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D015186:Hominidae / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics; D009928:Organ Specificity; D010281:Parathyroid Hormone / Q000235:genetics; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011323:Primates / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017455:Receptors, IgE / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics; D020218:Response Elements / Q000235:genetics; D013045:Species Specificity; D013601:T-Lymphocytes / Q000378:metabolism
D016827:CD8 Antigens; D010281:Parathyroid Hormone; D017455:Receptors, IgE; D011978:Receptors, Nicotinic; D002118:Calcium