Lesson 4. Evolution of the genome: comparative genomics

This week in class, we worked on comparing the genomes of different species, both at the level of point mutations and structural changes. With regard to the genome project you’re working on, and referencing the corresponding article:

Orthologous Genes

(a)  Do the authors of the study make any comparisons with a nearby species? Which one? How long ago did the two species diverge? If the article doesn’t indicate this, you can use TimeTree (http://www.timetree.org/) to find the speciation time between different species.

(b)  Obtain the coding sequence (CDS = only coding nucleotides between the ATG codon and the STOP codon) of a gene from your species and the coding sequence of the same gene from a nearby species (see the Genbank + RevTrans video). What is the general name given to two genes that are the same in two different species? What type of event generated them?

(c)  Align the two sequences using RevTrans or any other sequence alignment program (see the Genbank + RevTrans video). Make sure the resulting alignment is significant enough to calculate nucleotide evolution estimates (there should be almost no gaps; if you’re unsure, ask me!). Attach the alignment to your work. 

(d) Calculate the number of nucleotide substitutions per position (k) in the entire sequence and separately for each of the three codon positions. Apply a Ka/Ks test; do you think this gene is under the action of natural selection? Calculate the neutral substitution rate (synonymous) between these two species Note: You can, if you want, focus on a manageable and well-aligned region of the gene to do the count. This region must have synonymous and non-synonymous differences.

Paralogous Genes

(e)  Do the authors refer to any gene family in the genome of the species you’re studying? What is the general name given to all members of a gene family? What type of event generated them?

Syntenic Blocks

(f)  Do the authors show any type of graph representing syntenic blocks between two nearby species? Explain the graph in your own words. Do you think the two species exhibit highly or poorly conserved syntenic blocks compared to the human and mouse genomes shown in class? Would you expect these syntenic blocks to be more conserved between closer or more distant species phylogenetically? What types of mechanisms break these syntenic blocks?

With this task, we close the genome project! I hope this project has been an enriching and rewarding activity. From now until the final deadline, remember to re-read all the work submitted, add anything that’s missing, modify anything that needs improvement, and perfect the text quality.