Figure 1.

Spectrum of mtDNA mutations in somatic cells of PolG^mut/wt females and their germline transmission. (A) Schematic illustration of experimental design. To investigate the timing when purifying selection for mtDNA mutations operates, somatic mutations in the SF of PolG^mut/wt mothers (Mother) and germline transmitted variants in MII oocytes (MII), PolG^wt/wt blastocysts, PolG^wt/wt viable fetuses at E9.5, and PolG^wt/wt live offspring SF (Pup) were examined by mtDNA whole genome sequencing (MiSeq). (B) Quantification of mtDNA mutations in PolG^mut/wt female SFs (Mother, n = 20) and their MII oocytes (MII, n = 81), and PolG^wt/wt pup SFs (Pup, n = 20). (C) Quantification of heteroplasmy levels of mtDNA variants in PolG^mut/wt female SFs (n = 20) and their MII oocytes (n = 81) and PolG^wt/wt pup SFs (n = 20). (D) Quantification of mtDNA mutations in PolG^wt/wt blastocysts at E3.5 (n = 20) and PolG^wt/wt viable fetuses at E9.5 (n = 20). (E) Effect of heteroplasmy levels on germline transmission of mtDNA mutations in PolG^mut/wt females SFs (n = 20) and their MII oocytes (n = 81) and PolG^wt/wt pup SFs (n = 20). Purple, pink, and blue colors represent mtDNA variants with high (≥50%), moderate (10–49%), and low (<10–2%) heteroplasmy levels, respectively. In B–D, error bars are mean ± SEM; ns denotes P ≥ 0.05.