Fine Time Scaling of Purifying Selection on Human Nonsynonymous mtDNA Mutations Based on the Worldwide Population Tree and Mother-Child Pairs

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Rui Camacho (Author) FEUP; Bruno Cavadas (Author) Other; Pedro Soares (Author) Other; Andreia Brandão (Author) Other; Marta D. Costa (Author) Other; Verónica Fernandes (Author) Other; Joana I. Pereira (Author) Other; Teresa Rito (Author) Other; David C. Samuels (Author) Other; Luísa Pereira (Author) Other

Journal

Title: Human Mutation

Vol. 36

Pages: 1100-1111

ISSN: 1059-7794

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 12 Citations

Scopus - 12 Citations

Other information

Authenticus ID: P-00G-QCX

DOI: 10.1002/humu.22849

Abstract (EN): A high-resolution mtDNA phylogenetic tree allowed us to look backward in time to investigate purifying selection. Purifying selection was very strong in the last 2,500 years, continuously eliminating pathogenic mutations back until the end of the Younger Dryas (approximate to 11,000 years ago), when a large population expansion likely relaxed selection pressure. This was preceded by a phase of stable selection until another relaxation occurred in the out-of-Africa migration. Demography and selection are closely related: expansions led to relaxation of selection and higher pathogenicity mutations significantly decreased the growth of descendants. The only detectible positive selection was the recurrence of highly pathogenic nonsynonymous mutations (m.3394T>C-m.3397A>G-m.3398T>C) at interior branches of the tree, preventing the formation of a dinucleotide STR (TATATA) in the MT-ND1 gene. At the most recent time scale in 124 mother-children transmissions, purifying selection was detectable through the loss of mtDNA variants with high predicted pathogenicity. A few haplogroup-defining sites were also heteroplasmic, agreeing with a significant propensity in 349 positions in the phylogenetic tree to revert back to the ancestral variant. This nonrandom mutation property explains the observation of heteroplasmic mutations at some haplogroup-defining sites in sequencing datasets, which may not indicate poor quality as has been claimed.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12