Nullomers: really a matter of natural selection?
BACKGROUND
Nullomers are short DNA sequences that are absent from the genomes of humans and other species. Assuming that nullomers are the signatures of natural selection against deleterious sequences in humans, the use of nullomers in drug target identification, pesticide development, environmental monitoring, and forensic applications has been envisioned.


RESULTS
Here, we show that the hypermutability of CpG dinucleotides, rather than the natural selection against the nullomer sequences, is likely the reason for the phenomenal event of short sequence motifs becoming nullomers. Furthermore, many reported human nullomers differ by only one nucleotide, which reinforces the role of mutation in the evolution of the constellation of nullomers in populations and species. The known nullomers in chimpanzee, cow, dog, and mouse genomes show patterns that are consistent with those seen in humans.


CONCLUSIONS
The role of mutations, instead of selection, in generating nullomers cast doubt on the utility of nullomers in many envisioned applications, because of their dependence on the role of lethal selection on the origin of nullomers.
Acquisti
Claudia
C
Center for Evolutionary Functional Genomics, Arizona State University, Tempe, Arizona, United States of America.
Poste
George
G
Curtiss
David
D
Kumar
Sudhir
S
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D018899:CpG Islands; D004247:DNA / Q000235:genetics*; D004285:Dogs; D019143:Evolution, Molecular; D016678:Genome; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D002679:Pan troglodytes; D012641:Selection, Genetic; D013045:Species Specificity
D004247:DNA