林勇欣 副教授 國立交通大學 生物資訊及系統生物研究所

Yeong-Shin Lin, Associate Professor
Institute of Bioinformatics and Systems Biology
National Chiao Tung University
Hsinchu, Taiwan
Main Page Lab Members Lectures Resources Bioinformatics Center

分子演化 Molecular Evolution

Time:13:20 ~ 16:20 on Monday
Room:生科實驗館 BA301
Textbook:None
Grading:Homework 100%
Office hour:15:00 ~ 17:00 on Tuesday
15:00 ~ 17:00 on Thursday
TA:
Reference:以下圖書可在交大浩然圖書館借閱 (連結為電子書):
  • "Molecular evolution" by Wen-Hsiung Li; Sinauer Associates, 1997
  • "Molecular evolution :a phylogenetic approach" by Roderic D.M. Page & Edward C. Holmes; Blackwell Science, 1998
  • "Fundamentals of molecular evolution" by Dan Graur & Wen-Hsiung Li; Sinauer Associates, 2000
  • "Molecular evolution and phylogenetics" by Masatoshi Nei & Sudhir Kumar; Oxford University Press, 2000
  • "Data analysis in molecular biology and evolution" by Xuhua Xia; Kluwer Academic, 2000
  • "Bioinformatics and molecular evolution" by Paul G. Higgs & Teresa K. Attwood; Blackwell Pub., 2005
  • "Statistical methods in molecular evolution" by Rasmus Nielsen; Springer, 2005
  • "Computational molecular evolution" by Ziheng Yang; Oxford University Press, 2006

  • 2/26IntroductionPPT
    3/5Dynamics of Genes in PopulationsPPT
    3/12Dynamics of Genes in PopulationsPPT
    3/19Dynamics of Genes in Populations
    3/26Models of Nucleotide SubstitutionPPT
    4/2Models of Nucleotide SubstitutionPPT
    4/9Models of Amino Acid and Codon SubstitutionPPT
    4/16Models of Amino Acid and Codon SubstitutionPPT
    4/23AlignmentPPT
    4/30Phylogeny Reconstruction: Distance MethodsPPT
    5/7Phylogeny Reconstruction: Maximum ParsimonyPPT
    5/14Phylogeny Reconstruction: Maximum LikelihoodPPT
    5/21Comparison of Methods and Tests on TreesPPT
    5/28Molecular Clock and Estimation of Species Divergence TimesPPT
    6/4Neutral and Adaptive Protein EvolutionPPT
    6/11Bayesian MethodsPPT
    6/11DNA Polymorphism in PopulationsPPT

    Homework:

    E-mail your homework to me directly before the due date.
    HW 1.
    (due on 3/1)
    Collect the coding sequences of the HLA class I family, and their homologous sequences in other species (at least including human, chimpanzee, and macaque). Build a fasta file (*.fas). Use MEGA to perform a multiple sequences alignment and export a MEGA file (*.meg).
    Collect the coding sequences of the mitochondrial cytochrome b genes for as many mammalian species as you can (at least 30 species, including some closely related species, and some divergent species pairs). Also export a MEGA file.
    HW 2.
    (due on 3/8)
    Show the changes of allele frequencies over time for recessive alleles, dominant alleles, codominant alleles, overdominant alleles, and underdominant alleles under different selection coefficients and different initial allele frequencies.
    HW 3.
    (due on 3/15)
    If you can program, (a) draw a figure showing the changes in frequencies of alleles subject to random genetic drift in populations of different sizes (say, 10 different sizes). Try different initial allele frequencies. (b) Draw figures showing the probability distributions of allele frequencies in a diploid population of N=100 (with 10,000 replicates) for generation 1, 5, 20, 100, 500, and 2000. Also try different initial allele frequencies; If you cannot program, use Excel to do the second job. You can use N=5 (2N=10) and 100 replicates instead. You can survey generation 1, 3, 5, and 20 instead.
    HW 4.
    (due on 3/22)
    (a) Includ the factor of "selection" to repeat the last homework. (b) Calculate the probability of fixation in slide 19.
    HW 5.
    (due on 3/29)
    Use the "general substitution model" (the parameters refer to the substitution numbers observed in pseudogenes as shown in the PPT file) to display the nucleotide (A, T, C, G) probability (frequency) changes with time, as well as the change of the similarity, I. You can define different initial frequencies for A, T, C, and G.
    HW 6.
    (due on 4/5)
    Display the transitional difference (ts) and the transversional difference (tv) with time.
    Calculate the number of nucleotide differences, the proportion of nucleotide differences, JC69 one-parameter distance, and K80 two-parameter distance for (part of) the mitochondrial cytochrome b sequences you constructed in HW1. Compare your results with what MEGA computes for you.
    HW 7.
    (due on 4/12)
    Calculate S0, S2, S4, V0, V2, and V4 between human HLA-A and HLA-B genes for the first 240 nucleotides.
    HW 8.
    (due on 4/19)
    Use MEGA to calculate different genetic distances (number of transitions, number of transversions, JC69 one-parameter distance, K80 two-parameter distance, synonymous distance, nonsynonymous distance, and amino acid distance, etc.) for the mitochondrial cytochrome b sequences you constructed in HW1. Draw figures to compare these distances.
    HW 9.
    (due on 4/26)
    Align the two sequences manually with identity score = 5, transition score = -1, transversion score = -3, gap penalty = -7. Try different parameters.
    GATCTCGTCACTACTAATCGTACGTCATGCTGCT
    GATAGTATTACTAGTACGTTATTTGCCTGCT

    How about adding 2 nucleotides in the second sequence?
    GATCTCGTCACTACTAATCGTACGTCATGCTGCT
    GATAGTATTACTAGTACGTTATTTGCCTGCTGC
    HW 10.
    (due on 5/3)
    Build a UPGMA tree and a NJ tree manually based on the mitochondrial cytochrome b sequence alignment you constructed in HW 1 (you can select 6 ~ 10 sequences). You can select any distance model you like. Compare your results with what MEGA builds for you.
    HW 11.
    (due on 5/10)
    Build a NJ tree for the mitochondrial cytochrome b sequence alignment you constructed in HW 1 first. Use this topology and the parsimony principle to asign possible nucleotides on each internal node. You can just use the first 5 informative sites. Count the number of total substitutions on this tree. Compare this result with the Maximum Parsimony tree generated by MEGA. If they are different, illustrate what might be the reason.
    HW 12.
    (due on 5/17)
    Calculate and compare the log likelihood values for the two topologies in the last slide.
    HW 13.
    (due on 5/24)
    Build a phylogenetic tree based on the mitochondrial cytochrome b sequence alignment you constructed in HW 1 with 100 bootstrap repeats. Repeat this process 10 times. Construct another tree with 1000 bootstrap repeats. Also repeat this process 10 times. Compare these trees and their bootstrap supporting values. Identify the nodes with their bootstrap values less than 80 (or the couple nodes with the least supports). Based on these nodes, redraw a tree topology with polytomies. Try to list all possible bifurcating tree topologies based on these polytomies.
    HW 14.
    (due on 5/31)
    Use synonymous distances (Ks) and nonsynonymous distances (Ka) to build two NJ trees for the mitochondrial cytochrome b sequences. Compare the topologies and branch lengths of these two trees. Select some branches which may have different evolutionary rates. Perform the relative rate test on them. Build another NJ tree based on Ka with 6~10 species remained. Construct its timetree manually. Assume human and chimpanzee diverged 6 million years ago, try to estimate the divergence time for other nodes.



    計算生物實驗 Computational Biology Lab.

    Time:13:20 ~ 16:20 on Wednesday
    Room:生科實驗館 BA301
    Textbook:None
    Grading:Homework 100%
    Office hour:15:00 ~ 17:00 on Tuesday
    15:00 ~ 17:00 on Thursday
    TA:

    5/16Retrieve sequences from database
    Sequence alignment -- dot matrix
    PPT
    5/23Sequence alignment -- dot matrixPPT
    5/30Sequence alignment -- dynamic programmingPPT
    6/6Calculate pairwise distancesPPT
    6/13Construct a phylogenetic treePPT
    6/20Calculate codon usage biasPPT

    Homework:

    1. Retrieve the protein sequences of human hemoglobin (alpha 1) and hemoglobin (beta) from database
    2. Align these two sequences manually
    3. Build a dot matrix for these two sequences
    4. Using dynamic programming to align these two sequences
    5. Align the protein sequences of human hemoglobin (alpha 1) and hemoglobin (zeta). To generate the alignment represented in our textbook, how small the gap penalty should be assigned?
    6. Retrieve all the protein sequences of human and mouse (Mus musculus) hemoglobin from database, and align them based on the alignment result of hemoglobin (alpha 1) and hemoglobin (beta)
    7. Calculate pairwise distances
    8. Based on the calculated pairwise distances, construct a phylogenetic tree
    9. Retrieve all the DNA coding sequences of human and mouse (Mus musculus) hemoglobin from database, and subdivide them into 4 groups: human alpha, human beta, mouse alpha, and mouse beta
    10. Calculate GC content for the 4 groups
    11. Calculate GC1, GC2, and GC3 for the 4 groups
    12. Calculate codon usage frequencies for the 4 groups
    13. Retrieve ribosomal subunit genes and histone genes, and also calculate their GC, GC1, GC2, GC3, and codon usage frequencies



    遺傳學 Genetics

    Time:9:00 ~ 9:50 on Monday
    10:10 ~ 12:00 on Wednesday
    Room:工程六館 EF252
    Textbook:"Genetics - Analysis & principles" by Robert J. Brooker, 2012. Ed. 4 McGraw-Hill international
    "Genetics - From genes to genomes" by Leland H. Hartwell et al., 2015. Ed. 5 McGraw-Hill international
    Grading:期末考 33%
    Office hour:15:00 ~ 17:00 on Tuesday
    15:00 ~ 17:00 on Thursday
    TA:
    Reference: 課本網站 http://www.mcgrawhill.ca/highereducation/products/9780073525280/

    5/16 Digital Analysis of Genomes / [Genetics - From genes to genomes 5th Edition - chapter 9]
    GENOMICS I: ANALYSIS OF DNA / [Genetics - Analysis & principles 4th Edition - chapter 20]
    PPT
    5/21; 5/23 Analyzing Genomic Information / [Genetics - From genes to genomes 5th Edition - chapter 10]
    GENOMICS I: ANALYSIS OF DNA / [Genetics - Analysis & principles 4th Edition - chapter 20]
    PPT
    5/28; 5/30 Analyzing Genomic Information / [Genetics - From genes to genomes 5th Edition - chapter 10]
    GENOMICS I: ANALYSIS OF DNA / [Genetics - Analysis & principles 4th Edition - chapter 20]
    PPT
    6/4; 6/6 Variation and Selection in Populations / [Genetics - From genes to genomes 5th Edition - chapter 20]
    POPULATION GENETICS / [Genetics - Analysis & principles 4th Edition - chapter 24]
    PPT
    6/11; 6/13 Genetics of Complex Traits / [Genetics - From genes to genomes 5th Edition - chapter 21]
    QUANTITATIVE GENETICS / [Genetics - Analysis & principles 4th Edition - chapter 25]
    PPT
    6/20Final Examination

    Contact

    Office:+886-3-5712121 # 56960
    Fax:+886-3-5729288
    +886-3-5712121 # 56960
    Email:yslinfaculty.nctu.edu.tw
    Address:新竹市博愛街75號
    生科實驗二館 103室
    R103, BioLab-II, 75 Po-Ai Street, Hsinchu, Taiwan 30068


    Lab:+886-3-5712121 # 56961

    Lectures

    普通生物學(一)
    General Biology (I)

    計算生物實驗
    Computational Biology Lab.


    遺傳學
    Genetics


    演化生物學
    Evolutionary Biology

    分子演化
    Molecular Evolution


    Links

    NCBI
    EnsEMBL
    Genome OnLine Database
    Approved Sequencing Targets
    UCSC Genome Bioinformatics
    Stanford Genomic Resources
    TGI - The Gene Index
    J. Craig Venter Institute
    Broad Institute
    HapMap
    SGD
    SMD
    MIPS
    RCSB PDB
    SCOP
    ExPASy - SwissProt - PROSITE
    CE - Combinatorial Extension
    RepeatMasker

    MEGA
    PAUP
    PAML
    PhyML
    CONSEL
    MacClade
    MrBayes
    DAMBE
    LiKaKs
    Structure (population)
    DnaSP
    Arlequin
    MCL - a cluster algorithm for graphs
    The R Manuals
    SimpleR
    Chi-square Test
    Fisher's Exact Test
    Kolmogorov-Smirnov Test

    Nature
    Science
    PNAS
    PLoS Biology
    Current Biology
    Cell
    EMBO
    Nature Ecology & Evolution
    Nature Genetics
    Nature Biotechnology
    Trends in Genetics
    Genome Research
    Genome Biology
    Molecular Biology & Evolution
    Nucleic Acids Research
    Genetics
    Evolution
    Bioinformatics
    Journal of Molecular Biology
    Journal of Molecular Evolution
    MPE
    Proteins
    Gene

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    Main Page Lab Members Lectures Resources Bioinformatics Center