The rate and nature of mitochondrial DNA mutations in human pedigrees.
Cell
; 187(15): 3904-3918.e8, 2024 Jul 25.
Article
em En
| MEDLINE
| ID: mdl-38851187
ABSTRACT
We examined the rate and nature of mitochondrial DNA (mtDNA) mutations in humans using sequence data from 64,806 contemporary Icelanders from 2,548 matrilines. Based on 116,663 mother-child transmissions, 8,199 mutations were detected, providing robust rate estimates by nucleotide type, functional impact, position, and different alleles at the same position. We thoroughly document the true extent of hypermutability in mtDNA, mainly affecting the control region but also some coding-region variants. The results reveal the impact of negative selection on viable deleterious mutations, including rapidly mutating disease-associated 3243A>G and 1555A>G and pre-natal selection that most likely occurs during the development of oocytes. Finally, we show that the fate of new mutations is determined by a drastic germline bottleneck, amounting to an average of 3 mtDNA units effectively transmitted from mother to child.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linhagem
/
DNA Mitocondrial
Limite:
Female
/
Humans
/
Male
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article