Myosin Gene Mutation Correlates with Anatomical changes in the Human Lineage

Myosin Gene Myosin Gene Mutation Mutation

Correlates with Correlates with Anatomical Anatomical

changes in the changes in the Human LineageHuman Lineage

Some Background and Lots Some Background and Lots of Vocabularyof Vocabulary

Masticatory muscles – basically jaw Masticatory muscles – basically jaw musclesmuscles

These were a prominent adaptation in These were a prominent adaptation in AustralopithecusAustralopithecus and and ParanthropusParanthropus

AustralopithecusAustralopithecus – an extinct African – an extinct African hominid hominid

ParanthropusParanthropus – aka – aka Australopithecus Australopithecus robustus robustus


Both of these are in the family Both of these are in the family HominidaeHominidae

Hominidae – humans are the only Hominidae – humans are the only surviving member of surviving member of

this this familyfamily The muscles are much smaller in the The muscles are much smaller in the

genus genus HomoHomo..


This began in the Late Miocene This began in the Late Miocene periodperiod

Late Miocene – 10.4 -5 million years Late Miocene – 10.4 -5 million years ago ago

Australia ran into some Island at about 8 Australia ran into some Island at about 8 million years agomillion years ago

Polar ice caps were growing, sea levels Polar ice caps were growing, sea levels retreatingretreating

Plant and animal life was retreating inwardPlant and animal life was retreating inward Many plants and animals became extinctMany plants and animals became extinct


There was gracilization along with There was gracilization along with accelerated encephalization.accelerated encephalization.

Gracilization – decrease in bone sizeGracilization – decrease in bone size Encephalization – increase in brain Encephalization – increase in brain

sizesize

MethodMethod

Used degenerant PCR to obtain MYH16Used degenerant PCR to obtain MYH16 MYH16 is a human sarcomeric myosin geneMYH16 is a human sarcomeric myosin gene

Ran a BLAST searchRan a BLAST search The only match came from the human The only match came from the human

genome project (AC112711)genome project (AC112711) Used homology of sarcomeric myosins to Used homology of sarcomeric myosins to

determine the locus and to generate determine the locus and to generate some hypothetical sequences of relativessome hypothetical sequences of relatives

Myosin Heavy ChainMyosin Heavy Chain

Which One?Which One?

There was a frameshift deletion at There was a frameshift deletion at codon 660 of mRNAcodon 660 of mRNA

Why?Why? There are two possibilitiesThere are two possibilities

1)Rare allele1)Rare allele

2)Sequencing artifact2)Sequencing artifact

Which One?Which One?

Sequenced DNAsamples from humans Sequenced DNAsamples from humans from different geographic populations.from different geographic populations.

There was no difference.There was no difference.

Also, non-human primates have a highly Also, non-human primates have a highly conserved ACC (theronine) codonconserved ACC (theronine) codon

The frameshift creates an unstable The frameshift creates an unstable myosin head.myosin head.

Changes the 224kDaltons myosin heavy Changes the 224kDaltons myosin heavy chain to an unstable 76kDaltons chain to an unstable 76kDaltons fragment.fragment.

Conformation of ResultsConformation of Results

Had to macaque tissue instead of Had to macaque tissue instead of chimpanzeechimpanzee

Used isoform specific PCR primersUsed isoform specific PCR primers Found that Humans produced the Found that Humans produced the

sequences predicted and only in the sequences predicted and only in the facial musclesfacial muscles

MorphologyMorphology

The size of the muscles is obvious The size of the muscles is obvious from the structure of the skullsfrom the structure of the skulls

Masticatory musclesMasticatory muscles Temporalis musclesTemporalis muscles Masseter muscles Masseter muscles

http://egweb.bcgsc.ca/journal_club/http://egweb.bcgsc.ca/journal_club/2003_2004/pdfs/2003_2004/pdfs/short_report_040419_myosin_evolution.pdfshort_report_040419_myosin_evolution.pdf

Even the actual sizes of the fibers is Even the actual sizes of the fibers is differentdifferent

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The hypotrophy (basically the same The hypotrophy (basically the same as autotrophy) of the fibers is similar as autotrophy) of the fibers is similar to a rare diseaseto a rare disease inclusion body myopathy -3inclusion body myopathy -3 myosin gene mutation in MYH2myosin gene mutation in MYH2

In macaque the dominate isoform is In macaque the dominate isoform is specific to the masticatory musclesspecific to the masticatory muscles

Not found in humans, instead found Not found in humans, instead found products of MYH1, MYH2, and MYH7products of MYH1, MYH2, and MYH7

More MorphologyMore Morphology

The difference in the size of the The difference in the size of the fibers results from a reliance on fibers results from a reliance on translation of MYH1 and MYH2.translation of MYH1 and MYH2.

There has also been changes in the There has also been changes in the points of attachment sites (myostatin points of attachment sites (myostatin signaling)signaling)

This also reduces stress at across This also reduces stress at across patent sutures – we don’t have an patent sutures – we don’t have an much hypertrophymuch hypertrophy

When did this Happen?When did this Happen?

Align the sequences and deduce Align the sequences and deduce ancestoral sequencesancestoral sequences

There was a high ratio of There was a high ratio of synonymous to non-synonymous synonymous to non-synonymous mutationsmutations

Human-Chimpanzee divergance at 6-Human-Chimpanzee divergance at 6-7 million years ago7 million years ago

negative darwinian selection in all lineages negative darwinian selection in all lineages except humanexcept human

In ConclusionIn Conclusion

According to the fossil recordAccording to the fossil record Late Miocene had small chimpanzee brain Late Miocene had small chimpanzee brain

cases and large masticatory complexescases and large masticatory complexes Emphasis on it until Homo erectus has Emphasis on it until Homo erectus has

gracilization of the masticatory complexgracilization of the masticatory complex

The reduction of masticatory The reduction of masticatory strength allowed encephalizationstrength allowed encephalization

When did this happen?When did this happen?

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

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Myosin Gene Mutation Correlates with Anatomical changes in the Human Lineage