A high-resolution map of human evolutionary constraint using 29 mammals.
Nature
; 478(7370): 476-82, 2011 Oct 12.
Article
em En
| MEDLINE
| ID: mdl-21993624
ABSTRACT
The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering â¼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for â¼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Genoma Humano
/
Genoma
/
Evolução Molecular
/
Mamíferos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nature
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos