Myosin Gene Mutation Correlates with Anatomical changes in the Human Lineage

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

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

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

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

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

Myosin Heavy Chain

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

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

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

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

/pdfs/short_report_040419_myosin_evolution. pdf /pdfs/short_report_040419_myosin_evolution. pdf

Even the actual sizes of the fibers is different Even the actual sizes of the fibers is different

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

More Morphology The difference in the size of the fibers results from a reliance on translation of MYH1 and MYH2. 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) 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 This also reduces stress at across patent sutures – we don’t have an much hypertrophy

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

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

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