Evolutionary conservation and modulation of a juvenile growth-regulating genetic program.
Body size varies enormously among mammalian species. In small mammals, body growth is typically suppressed rapidly, within weeks, whereas in large mammals, growth is suppressed slowly, over years, allowing for a greater adult size. We recently reported evidence that body growth suppression in rodents is caused in part by a juvenile genetic program that occurs in multiple tissues simultaneously and involves the downregulation of a large set of growth-promoting genes. We hypothesized that this genetic program is conserved in large mammals but that its time course is evolutionarily modulated such that it plays out more slowly, allowing for more prolonged growth. Consistent with this hypothesis, using expression microarray analysis, we identified a set of genes that are downregulated with age in both juvenile sheep kidney and lung. This overlapping gene set was enriched for genes involved in cell proliferation and growth and showed striking similarity to a set of genes downregulated with age in multiple organs of the juvenile mouse and rat, indicating that the multiorgan juvenile genetic program previously described in rodents has been conserved in the 80 million years since sheep and rodents diverged in evolution. Using microarray and real-time PCR, we found that the pace of this program was most rapid in mice, more gradual in rats, and most gradual in sheep. These findings support the hypothesis that a growth-regulating genetic program is conserved among mammalian species but that its pace is modulated to allow more prolonged growth and therefore greater adult body size in larger mammals.
Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development Microarray Core Facility, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, MSC-1103; Building 10, Room 1-3330, Bethesda, Maryland 20892, USA Department of Pediatrics and the Reproductive Sciences Program, The University of Michigan, Ann Arbor, Michigan, USA.
Angela
A
Delaney
Vasantha
V
Padmanabhan
Geoffrey
G
Rezvani
Weiping
W
Chen
Patricia
P
Forcinito
Crystal S F
CS
Cheung
Jeffrey
J
Baron
Julian C K
JC
Lui
D000818:Animals; D005075:Biological Evolution; D049628:Body Size / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D007668:Kidney / Q000254:growth & development*; D008168:Lung / Q000254:growth & development*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep / Q000235:genetics / Q000254:growth & development
evolutionary conservation; gene expression; growth limitation; phylogeny