Genome-wide inference of natural selection on human transcription factor binding sites.
Nat Genet
; 45(7): 723-9, 2013 Jul.
Article
en En
| MEDLINE
| ID: mdl-23749186
ABSTRACT
For decades, it has been hypothesized that gene regulation has had a central role in human evolution, yet much remains unknown about the genome-wide impact of regulatory mutations. Here we use whole-genome sequences and genome-wide chromatin immunoprecipitation and sequencing data to demonstrate that natural selection has profoundly influenced human transcription factor binding sites since the divergence of humans from chimpanzees 4-6 million years ago. Our analysis uses a new probabilistic method, called INSIGHT, for measuring the influence of selection on collections of short, interspersed noncoding elements. We find that, on average, transcription factor binding sites have experienced somewhat weaker selection than protein-coding genes. However, the binding sites of several transcription factors show clear evidence of adaptation. Several measures of selection are strongly correlated with predicted binding affinity. Overall, regulatory elements seem to contribute substantially to both adaptive substitutions and deleterious polymorphisms with key implications for human evolution and disease.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Selección Genética
/
Factores de Transcripción
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Genoma Humano
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2013
Tipo del documento:
Article