Megabase deletions of gene deserts result in viable mice.
The functional importance of the roughly 98% of mammalian genomes not corresponding to protein coding sequences remains largely undetermined. Here we show that some large-scale deletions of the non-coding DNA referred to as gene deserts can be well tolerated by an organism. We deleted two large non-coding intervals, 1,511 kilobases and 845 kilobases in length, from the mouse genome. Viable mice homozygous for the deletions were generated and were indistinguishable from wild-type littermates with regard to morphology, reproductive fitness, growth, longevity and a variety of parameters assaying general homeostasis. Further detailed analysis of the expression of multiple genes bracketing the deletions revealed only minor expression differences in homozygous deletion and wild-type mice. Together, the two deleted segments harbour 1,243 non-coding sequences conserved between humans and rodents (more than 100 base pairs, 70% identity). Some of the deleted sequences might encode for functions unidentified in our screen; nonetheless, these studies further support the existence of potentially 'disposable DNA' in the genomes of mammals.
Nóbrega
Marcelo A
MA
DOE Joint Genome Institute Walnut Creek, California 94598, USA.
Zhu
Yiwen
Y
Plajzer-Frick
Ingrid
I
Afzal
Veena
V
Rubin
Edward M
EM
D000818:Animals; D002872:Chromosome Deletion; D033481:Chromosomes, Mammalian / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D020043:Genes, Essential / Q000235:genetics; D016678:Genome; D006720:Homozygote; D006801:Humans; D008136:Longevity / Q000235:genetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010641:Phenotype; D012098:Reproduction / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics*