Signals of Variation in Human Mutation Rate at Multiple Levels of Sequence Context.
Mol Biol Evol
; 36(5): 955-965, 2019 05 01.
Article
en En
| MEDLINE
| ID: mdl-30753705
ABSTRACT
Our understanding of the human mutation rate helps us build evolutionary models and interpret patterns of genetic variation observed in human populations. Recent work indicates that the frequencies of specific polymorphism types have been elevated in Europe, and that many more, subtler signatures of global polymorphism variation may yet remain unidentified. Here, we present an analysis of the 1000 Genomes Project supported by analysis in the Simons Genome Diversity Panel, suggesting additional putative signatures of mutation rate variation across populations and the extent to which they are shaped by local sequence context. First, we compiled a list of the most significantly variable polymorphism types in a cross-continental statistical test. Clustering polymorphisms together, we observe three sets that showed distinct shared patterns of relative enrichment among ancestral populations, and we characterize each one of these putative "signatures" of polymorphism variation. For three of these signatures, we found that a single flanking base pair of sequence context was sufficient to determine the majority of enrichment or depletion of a polymorphism type. However, local genetic context up to 2-3 bp away contributes additional variability and may help to interpret a previously noted enrichment of certain polymorphism types in some East Asian groups. Moreover, considering broader local genetic context highlights patterns of polymorphism variation, which were not captured by previous approaches. Building our understanding of mutation rate in this way can help us to construct more accurate evolutionary models and better understand the mechanisms that underlie genetic change.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Polimorfismo Genético
/
Genoma Humano
/
Tasa de Mutación
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Biol Evol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2019
Tipo del documento:
Article
País de afiliación:
Canadá