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Asymmetric Sequence Divergence of Duplicate Genes

Asymmetric Sequence Divergence of Duplicate Genes. Experimented By: Gavin Conant and Andreas Wagner Presented By: Jennifer Case and Jonathan Hobbs. What are Gene Duplications?. Duplication: More than one copy of a particular chromosomal segment in a chromosome set. Why Study Duplications?.

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Asymmetric Sequence Divergence of Duplicate Genes

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  1. Asymmetric Sequence Divergence of Duplicate Genes Experimented By: Gavin Conant and Andreas Wagner Presented By: Jennifer Case and Jonathan Hobbs

  2. What are Gene Duplications? • Duplication: More than one copy of a particular chromosomal segment in a chromosome set

  3. Why Study Duplications? • Why are they important? • What can duplications tell us?

  4. Divergence • Divergence is an important process for driving evolutionary changes.

  5. Necessary Vocabulary • Ka - amino acid (non-synonymous) substitutions • Ks - silent (synonymous) substitutions • P - probability of reoccurrances happening by chance alone • X2 - a goodness-of-fit test • r - a statistical association • s - a statistical association

  6. Methods Considered • Nucleotide-based tests • Amino Acid-based tests • Codon-based tests

  7. Purpose of this experiment • 1. Test the number of pairs with asymmetric Ka values that can be explained by the 5% error rate of our individual hypothesis tests. • 2. Test to see if asymmetric a.a. divergence is coupled to greater functional divergence in one of two duplicate genes.

  8. First Hypothesis • “…the number of pairs with asymmetrical Ka values could be explained by a 5% error rate…”

  9. Methods for Hypothesis 1 • Codon Model--allows for the possibility that duplicate genes evolve independently. • 2 duplicate genes and one outgroup gene are found

  10. Methods for Hypothesis 1 • Likelihood Ratio Test • x2 analysis • P (probability) significance

  11. [Ka] asymmetrical in 5% error • Everything that was more significant than 5% supports the hypothesis, everything 5% or under rejects it.

  12. Results for Hypothesis 1 • Special results: • Fission Yeast • Outgroup gene is very distant from duplicates • Fruit Fly • Lysozyme D Gene Family • Chitanase • Worm • 7-helix transmembrane chemoreceptor domains

  13. Results for Hypothesis 1 Unsaturated nucleotide sequence- Sites that have not begun to back mutate.

  14. Discussion for Hypothesis 1 • An average genome contains at least 20% of gene duplicates that diverge asymmetrically. • Larger numbers with larger data (ex. worm and fruit fly) • Differs from other studies • different approaches • different models

  15. Second Hypothesis • “…tested the hypothesis that asymmetric amino acid divergence is coupled to greater gene expression divergence in one of two duplicate genes.”

  16. Methods for Hypothesis 2 • 2 questions were asked in this part of the experiment • 1.) Is there association between sequence asymmetry and expression divergence? • 2.) Is there association between sequence asymmetry and asymmetry of expression divergence?

  17. Methods for Hypothesis 2 • To answer first question: • Only used the two duplicates because of lack of sequence data. • Used eleven different experimental conditions for data acquisition. • Found log2-transformed ratios • Compared normalized difference to the different in the transformed ratios.

  18. Methods for Hypothesis 2 • To answer 2nd question: • gene under-expression by at least two-fold • Compared Found value to the normalized value

  19. Results for Hypothesis 2 • mRNA microarray data • no significant correlation between degree of asymmetry and divergence in expression level • calculated statistical association between asymmetry in expression level and asymmetry in Ka • Found no significant association

  20. Discussion for Hypothesis 2 • What is the significance of having no significant correlation between sequence asymmetry and: • expression divergence • asymmetry of expression divergence

  21. Selection Process • 2 Forces can drive asymmetric divergence • relaxed selective constraints • sequence divergence is neutral • directional or positive selection • the rate of Ka/Ks is greater than 1 • advantageous mutations play a key role in divergence.

  22. Results for Selection Process • Statistical association between asymmetry in amino acid divergence and evolutionary constraints on duplicate pairs. (Ka/Ks)

  23. Results for Selection Process • They found: • in yeast • weakly significant correlation between asymmetry and selective constraints • in fruit fly and worm • highly significant correlation between asymmetry and selective constraints

  24. To Test for Positive Selection • Triplet-based Method vs. Pairwise Method

  25. Discussion for Selection Process • It appears as though relaxed selective constraints may be largely responsible for asymmetric divergence • Not necessarily the case! • Positive Selection acts fast and in a small area so it can be difficult to detect. • Need more than just the sequence to tell if positive selection has taken place. • Probably BOTH are largely responsible depending on which gene is in question

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