BIOCHEM 4/6Y03  -   Genomes and Evolution


Paul Higgs


Schedule for Winter 2014: Mon 11.30-13.20, Wed - 11.30-12.20 - KTH B132


This course will focus on key issues in molecular evolution, and will introduce the bioinformatics methods that are necessary to answer these questions. Now that hundreds of complete genomes are available, what have we learned? Which genes are shared between organisms? How do we build evolutionary trees? Is there a molecular clock? What are the evolutionary relationships between bacteria? How often does horizontal gene transfer occur? What are the origins of organelles and their genomes? How does the human genome compare with other species? What do microarray and proteomics experiments tells us about how organisms work at the whole genome level?


Prerequisites: BIOCHEM 2B03 or 3G03

Antirequisite: BIOLOGY 4DD3


Recommended text:

Lectures will be based on material included in the book ‘Bioinformatics and Molecular Evolution’ by P.G.Higgs and T.K.Attwood.


Lecture Contents


1. What is bioinformatics? Data explosions. The relationship between molecular evolution and bioinformatics. The relevance of bioinformatics for genomics, microarrays and proteomics.

Read: Chapter 1


2. Molecular Evolution and Population Genetics. Sequence variation within and between populations. Random drift and fixation. Neutral evolution and selection.

Read: Chapter 3

Examples related to Human evolution - mitochondria and Y chromosomes: Adam and Eve


3. Models for nucleic acid sequence evolution. Synonymous and non-synonymous substitutions. Models for protein sequence evolution. Scoring systems for sequence alignment.

Read: Chapter 4 and Chapter 2, sections 2.4-2.6.


4. Methods of molecular phylogenetics. Comparison of distance matrix, parsimony, maximum likelihood and Bayesian methods. Biological examples and controversies in phylogenetics. Mammalian orders. Animal Phyla. Major Eukaryotic groups. Molecular Clocks.

Read: Chapter 8 and Lecture notes: phylogenynotes.ppt


5. Codon Usage and Base frequency variation among genomes

Lecture Notes: CodonsAndMitochondria.ppt

Useful papers for details:

Sharp - Table of RSCU values in various organisms

Duret - tRNAs and codon usage in C. elegans

Akashi - codon usage in yeast as a function of gene expression level

Ran and Higgs - Variation of codon usage with tRNA content in bacteria

Jia and Higgs - Context-dependent mutation in mitochondria

Xu et al - Variations in mitochondrial gene order


6. Evolution of the Genetic Code

Notes: GeneticCodeLectures.ppt

Useful papers:

Sengupta et al - Codon reassignment in mitochondrial genomes


7. Sequence alignment. Database searching.

Read: Chapter 6 and Chapter 7


8. Bacterial genome evolution. Horizontal transfer.

Read: Chapter 12

Notes: BacterialGenomes.ppt

Two views of the Tree of Life:



Bacterial Genomes:








Three written assignments - each worth 15%

Midterm test - worth 15%

Final Exam - worth 40%


Additional work for graduate students - Graduate students will complete a literature review on a chosen topic. This will be worth 30% and the other parts of the course will be scaled down to 70%.


Download Assignment 1 - Assignment1.doc . Please hand in on Mon 27th Jan. You will need the following paper for this assignment: Ingman.pdf


Download Assignment 2 - Assignment2.doc . Please hand in on Mon 24th Feb. You will need the following papers: Subramanian , Sharp , Yang


Midterm - in class on Wed March 12th. Topics will be points 2,3,4,5 on the lecture list above.


Download Assignment 3 - Assignment3.doc . Please hand in on Mon 31st March. You will need the following papers: Hao & Golding , McCutcheon (and the Sengupta paper in no. 6 above may be useful)


EXAM HINTS: For the exam, please focus on the following topics -

·         Sequence alignment methods & PAM matrices

·         Bacterial genome evolution

·         Horizontal gene transfer

·         Evolution of the genetic code



Reminder on university policies regarding academic dishonesty

Academic dishonesty consists of misrepresentation by deception or by
other fraudulent means and can result in serious consequences, e.g. the
grade of zero on an assignment, loss of credit with a notation on the
transcript (notation reads "Grade of F assigned for academic
dishonesty"), and/or suspension or expulsion from the university.

It is your responsibility to understand what constitutes academic
dishonesty. For information on the various kinds of academic dishonesty
please refer to the Academic Integrity Policy, specifically Appendix 3,
located at

The following illustrates only three forms of academic dishonesty:
1. Plagiarism, e.g. the submission of work that is not one's own or for
   which credit has been obtained.
2. Improper collaboration in group work.
3. Copying or using unauthorized aids in tests and examinations.