Rapid mitochondrial DNA segregation in primate preimplantation embryos precedes somatic and germline bottleneck.
The timing and mechanisms of mitochondrial DNA (mtDNA) segregation and transmission in mammals are poorly understood. Genetic bottleneck in female germ cells has been proposed as the main phenomenon responsible for rapid intergenerational segregation of heteroplasmic mtDNA. We demonstrate here that mtDNA segregation occurs during primate preimplantation embryogenesis resulting in partitioning of mtDNA variants between daughter blastomeres. A substantial shift toward homoplasmy occurred in fetuses and embryonic stem cells (ESCs) derived from these heteroplasmic embryos. We also observed a wide range of heteroplasmic mtDNA variants distributed in individual oocytes recovered from these fetuses. Thus, we present here evidence for a previously unknown mtDNA segregation and bottleneck during preimplantation embryo development, suggesting that return to the homoplasmic condition can occur during development of an individual organism from the zygote to birth, without a passage through the germline.
Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
Hyo-Sang
HS
Lee
Hong
H
Ma
Rita Cervera
RC
Juanes
Masahito
M
Tachibana
Michelle
M
Sparman
Joy
J
Woodward
Cathy
C
Ramsey
Jing
J
Xu
Eun-Ju
EJ
Kang
Paula
P
Amato
Georg
G
Mair
Ralf
R
Steinborn
Shoukhrat
S
Mitalipov
D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000378:metabolism; D001757:Blastomeres / Q000166:cytology / Q000378:metabolism; D002455:Cell Division / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018628:Gene Dosage / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D008253:Macaca mulatta / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism; D011247:Pregnancy
D004272:DNA, Mitochondrial