Myosin Gene Mutation Correlates with Anatomical changes in the Human Lineage

1. Myosin Gene Mutation Correlates with Anatomical changes in the Human Lineage

2. Some Background and Lots of Vocabulary • Masticatory muscles – basically jaw muscles • These were a prominent adaptation in Australopithecus and Paranthropus • Australopithecus – an extinct African hominid • Paranthropus – aka Australopithecus robustus

3. Some Background and Lots of Vocabulary • Both of these are in the family Hominidae • Hominidae – humans are the only surviving member of this family • The muscles are much smaller in the genus Homo.

4. Some Background and Lots of Vocabulary • This began in the Late Miocene period • Late Miocene – 10.4 -5 million years ago • Australia ran into some Island at about 8 million years ago • Polar ice caps were growing, sea levels retreating • Plant and animal life was retreating inward • Many plants and animals became extinct

5. Some Background and Lots of Vocabulary • There was gracilization along with accelerated encephalization. • Gracilization – decrease in bone size • Encephalization – increase in brain size

6. Method • Used degenerant PCR to obtain MYH16 • MYH16 is a human sarcomeric myosin gene • Ran a BLAST search • The only match came from the human genome project (AC112711) • Used homology of sarcomeric myosins to determine the locus and to generate some hypothetical sequences of relatives

7. Myosin Heavy Chain

8. Which One? • There was a frameshift deletion at codon 660 of mRNA • Why? • There are two possibilities 1)Rare allele 2)Sequencing artifact

9. Which One? • Sequenced DNAsamples from humans from different geographic populations. • There was no difference. • Also, non-human primates have a highly conserved ACC (theronine) codon • The frameshift creates an unstable myosin head. • Changes the 224kDaltons myosin heavy chain to an unstable 76kDaltons fragment.

11. Conformation of Results • Had to macaque tissue instead of chimpanzee • Used isoform specific PCR primers • Found that Humans produced the sequences predicted and only in the facial muscles

12. Morphology • The size of the muscles is obvious from the structure of the skulls • Masticatory muscles • Temporalis muscles • Masseter muscles

13. http://egweb.bcgsc.ca/journal_club/2003_2004/pdfs/short_report_040419_myosin_evolution.pdfhttp://egweb.bcgsc.ca/journal_club/2003_2004/pdfs/short_report_040419_myosin_evolution.pdf

14. Even the actual sizes of the fibers is different

15. [insert title here] • The hypotrophy (basically the same as autotrophy) of the fibers is similar to a rare disease  inclusion body myopathy -3 • myosin gene mutation in MYH2 • In macaque the dominate isoform is specific to the masticatory muscles • Not found in humans, instead found products of MYH1, MYH2, and MYH7

16. More Morphology • The difference in the size of the fibers results from a reliance on translation of MYH1 and MYH2. • There has also been changes in the points of attachment sites (myostatin signaling) • This also reduces stress at across patent sutures – we don’t have an much hypertrophy

17. When did this Happen? • Align the sequences and deduce ancestoral sequences • There was a high ratio of synonymous to non-synonymous mutations • Human-Chimpanzee divergance at 6-7 million years ago negative darwinian selection in all lineages except human

18. In Conclusion • According to the fossil record • Late Miocene had small chimpanzee brain cases and large masticatory complexes • Emphasis on it until Homo erectus has gracilization of the masticatory complex • The reduction of masticatory strength allowed encephalization

19. When did this happen? • The formula reveals that this mutation occurred 2.4 +/- 0.3 million years ago.