Human Mitochondrial Molecular Biology Center for Advanced Studies at Wheeler High School Post-AP DNA/Genetics

Mitochondrial Genetics mitochondrial proteins are encoded in the nucleus, made in the cytosol and imported into the mitochondria

Mitochondrial Genetics Interest in mitochondrial genetics comes mostly from: interest in diseases caused by mutations in mDNA interest in human history

Mitochondrial Genetics 14kb - 42kb in size No recombination Little intergenic DNA (‘junk’ DNA) No introns Small, double stranded circular chromosome Own genetic code

Evolution of Mitochondria Endosymbiotic Theory Anaerobic prokaryotic cell engulfed an aerobic bacterium and formed a symbiotic relationship.

Number of Mito Per Cell Most somatic cells ,000 Lymphocyte1000 Oocytes 100,000 Sperm few hundred No mitochondria in red cells and some terminally differentiated skin cells

Human Evolution and mtDNA Mitochondria divide via binary fission they are inherited mainly from the mother: >99% of our mitochondria are derived from those (1000 or so) present in our mother’s ovum

Why Maternal? Sperm mitochondria are shed before entry of the sperm nucleus. All mitochondrial in the zygote are contributed by the egg cell. Less than 0.01% is paternal

mtDNA Mutations Mutations in the mtDNA are passed on from mother to child.

Human History Extrapolating this in evolutionary terms, this means that all mitochondria came from a “single” ancestral female - the so-called “Mitochondrial Eve”. References: Proceedings of National Academy Sci (USA) 91:8739 (1994) Science 279: 28 (1998)

Human History Depends on: High rate (particularly in the D loop region) Maternal transmission No recombination This allows the origins of female ancestors to be deduced.

Region of Variation D-loop: origin of mtDNA replication Human evolution can be traced by analysis of the base sequence in a small part of the mitochondrial genome which does not encode a gene and which is quite variable. - the so-called D-loop.

Human Evolution & mtDNA The D-Loop of the mtDNA is the start of replication/transcription site and contains bp Unlike the rest of mtDNA in humans, which is highly conserved, this region is very variable between people It also has a very high frequency of change during evolution (about 2% per million years)

Human Evolution & mtDNA By comparing different groups, we can get a glimpse of human evolutionary lines. African individuals have more variability between each other than do Asians, indicating that the former have had more time to accumulate changes - ie, the Africans are a more ancient group.

mtDNA & Alu Insert Analysis

mtDNA Testing - Ancestry