Genomics at Mount Holyoke College
Lessons Learned and Future Plans
Bio. 302 Molecular Evolution Fall 2011
Amy Frary, 120C Carr, x3015, email: afrary
Class Meetings: Tuesday and Thursday, 8:35-9:50, 218 Clapp
Labs: Tuesday, 1:15-4:05, 317 Reese
lab TA: Natasha Naidoo, firstname.lastname@example.org
Texts: Bromham, L. Reading the Story in DNA, Oxford University Press, 2008.
Hall, B.G. Phylogenetic Trees Made Easy: A How-To Manual, Sinauer, 2011 (required
Exams: There will be two exams held during regular class time on October 6, and November 10. The final exam will be taken during the exam period and will mostly cover material from the last unit with some cumulative questions.
In-class Discussions: Several times during the semester, we will spend half of a class period discussing pairs of complementary review papers. These papers have been selected to provide additional information and alternative perspectives on some of the topics addressed in class. While all students should reach each paper, to structure these discussion sessions, the class will be split in half, with each group of students responsible for presenting the material in their paper to the other half of the class. Within a group, individual students should take charge of their own section of the paper, coming to class prepared to provide an overview on the key concepts/new ideas/different perspectives offered in that section as well as questions designed to stimulate discussion.
Lecture Topics & Associated Readings (journal articles are posted on ella):
• Introduction to molecular evolution
Bromham, ch. 1
Zuckerkandl & Pauling (1965) Molecules as documents of evolutionary history.
Callaway (2011) Ancient DNA reveals secrets of human history.
• Genes, gene structure & mutations
Bromham, pp. 38-50, 62-77, 86-88, 121-123, 95-99
• Dynamics of genes in populations; natural selection & genetic drift
Bromham, pp. 140-180
Zheng and Gerstein (2007) The ambiguous boundary between genes and
pseudogenes: the dead rise up, or do they?
Sasidharan & Gerstein (2008) Protein fossils live on as RNA.
• Evolutionary changes in DNA sequences; patterns & rates of substitutions; molecular
Bromham, pp. 207-215, ch. 8
Arendt & Reznick (2007) Convergence and parallelism reconsidered: What have
we learned about the genetics of adaptation?
Kumar (2005) Molecular clocks: four decades of evolution.
Bromham (2009) Why do species vary in their rate of molecular evolution?
• Molecular phylogenetics; methods
Bromham, ch. 7
Gregory (2008) Understanding evolutionary trees.
• Evolution of new genes, new functions; gene duplication; concerted evolution vs. birth-and-
Vavouri et al. (2008) Widespread conservation of genetic redundancy during a
billion years of eukaryotic evolution.
Qian et al. (2010) Maintenance of duplicate genes and their functional redundancy by
• Transposable elements; genetic & evolutionary effects; horizontal gene transfer
• Genome evolution; genome size & organization
Bennetzen et al. (2005) Mechanisms of recent genome size variation in flowering
Ray et al. (2010) Reading between the LINEs to see into the past.
• Morphological evolution; QTL mapping; evolutionary developmental biology
Nadeau & Jiggins (2011) A golden age for evolutionary genetics? Genomic studies of
adaptation in natural populations.
Labs: The laboratory for this course will consist of computer-based exploration of online sequence databases and analysis tools, including DNA sequence annotation, BLAST searches, and sequence alignment, as well as evolutionary tree reconstruction. The lab assignments will consist of a brief introduction to BLAST (a tool you will be using through the semester) and two projects as described below.
For the first project, you will work with a partner to annotate a genomic DNA sequence, a fosmid containing about 40-50 kb from the Drosophila dot chromosome sequencing project of the Genomics Education Partnership (GEP). The GEP is a collaboration between Washington University in St. Louis and a number of predominantly undergraduate institutions designed to engage students in genomics. The current research of the GEP is aimed at elucidating the structure and function of the fourth (or dot) chromosome of Drosophila. This chromosome is largely heterochromatic but does contain euchromatic (gene-containing) domains. Your goal is to use sequence homology and computational predictions to identify the gene(s) within your sequence and delineate the boundaries of your gene(s) and its exons. Thus you will be creating gene model for your fosmid sequence. There is a worksheet for you and your partner to complete during the two annotation labs on September 27 and October 4. That worksheet is due in lab on October 18.
You will then spend the next seven labs learning some of the techniques of molecular evolutionary analysis by working through several chapters of the book Phylogenetic Trees Made Easy: A How-To Manual. This book serves as an excellent introduction to MEGA 5, a software program for finding homologous sequences, aligning those sequences, and creating evolutionary trees from sequence alignments using a variety of methods. As you work through the book using the files available at the book website, you will also by applying the techniques you learn to a unknown/mystery sequence, which I will give you in lab on October 18 (one sequence per student). The goal of the second lab project is for you to identify and explore evolutionarily interesting aspects of your mystery sequence. The results of your analyses will be turned in weekly. Those results, combined with your reading of background literature relevant to your sequence, will be written up in the form of a report due on the last day of class (December 13). The report should include the following sections: Description of the Sequence (the identity and background information on the sequence as well as what question you decided to investigate), Description of the Analysis (the techniques you used to analyze the sequence and the rationale behind your choice of methods), Results of the Analysis, and Discussion (the implications & biological meaning of your results). You will also present your results to the class in a 10-15 minute oral presentation on December 13.
Schedule of Labs:
Sept. 13 no lab
Sept. 20 Introduction to BLAST (posted on ella)
assignment: answer questions on BLAST handout (due in lab next week, 10 pts.)
BLAST exercise was developed using GEP materials: An Introduction to NCBI BLAST)
Sept. 27 Genomic Annotation Project (from GEP website)
Annotation exercise was developed using GEP materials: A Simple Annotation Problem and BLAST Exercise: Detecting & Interpreting Genetic Homology
Oct. 4 Continue Genomic Annotation
assignment: complete annotation worksheet (due Oct. 18, 25 pts.)
Oct. 11 no lab (fall break)
Oct. 18 Tutorial: Estimate a Tree (ch. 2, Phylogenetic Trees Made Easy); receive mystery sequence
assignment: write a brief description of your mystery sequence, what is it? (due in lab next
week, 10 pts.)
Oct. 25 Acquiring the Sequences (ch. 3, Phylogenetic Trees Made Easy)
assignment: lists of putative homologs from BLAST searches of the nucleotide &
protein databases, include Max score, Total score, Query coverage & E values as well as program used and database searched (these sequences should also be imported into the MEGA Alignment Explorer) (due in lab next week, 10 pts.)
Nov. 1 Aligning the Sequences (ch. 4, Phylogenetic Trees Made Easy)
assignment: codon alignment of your homologous sequences saved as .meg files,
screenshot of the matrix showing pairwise distances between the sequences,
average percent amino acid identity in your alignment (due in lab next week, 10 pts.)
Nov. 8 Estimating Phylogenetic Trees: Neighbor Joining Trees (ch. 5 & 6, Phylogenetic Trees Made
assignment: JC distance for your data, unrooted NJ tree, bootstrapped consensus tree,
majority rule tree, describe the key differences among the trees (due in lab next week, 10 pts.)
Nov. 15 Drawing Phylogenetic Trees (ch. 7, Phylogenetic Trees Made Easy)
assignment: rooted NJ tree presented in a clear, readable format, describe your rationale in
selecting the root of your tree, due in lab next week (due in lab next week, 10 pts.)
Nov. 22 Parsimony (ch. 8, Phylogenetic Trees Made Easy)
assignment: rooted consensus tree estimated by MP, bootstrapped consensus MP tree, describe
the key differences between the trees, (due in lab next week, 10 pts.)
Nov. 29 Maximum Likelihoood (ch. 9, Phylogenetic Trees Made Easy)
assignment: rooted ML tree with branch lengths, bootstrapped ML tree, describe which model
you used and the key differences between the trees (due in lab next week, 10 pts.)
Dec. 6 free time to work on independent projects
Dec. 13 Oral Presentations