Web document 13-1. Approaches to genomics: five perspectives

As we survey the tree of life, consider these five perspectives:

Approach I: catalog genomic information

Genome size; number of chromosomes; GC content; isochores; number of genes; repetitive DNA; unique features of each genome

Techniques: genomic DNA sequencing; assembly; annotation; intrinsic, extrinsic gene prediction

Approach II: catalog comparative genomic information

Orthologs and paralogs; COGs; lateral gene transfer

Techniques: comparative genomics; whole chromosome, whole genome alignment

Approach III: biological principles; function; mechanisms of evolution

How genome size is regulated; polyploidization; birth and death of genes; neutral theory of evolution; positive and negative selection; speciation

Techniques: molecular phylogeny; tests of selection; BLAST for evidence of duplication

Approach IV: human disease relevance

Mechanisms by which organisms cause disease, and types of responses

Techniques: various including SNPs; linkage; association; model organisms

Approach V: bioinformatics aspects

Algorithms, databases, websites

For a course I teach, students analyze a genome in depth as follows.

[1] Select any genome.

[2] Prepare a written document in which you describe it from the five perspectives outlined in the course:

1) Catalog genomic information (genome size; number of chromosomes; GC content; isochores; number of genes; repetitive DNA; unique features)

2) Catalog comparative genomic information (ladder-and-constellation approach;

orthologs and paralogs; COGs; lateral gene transfer)

3) Mechanisms of evolution (how genome size is regulated; polyploidization; birth and death of genes; neutral theory of evolution; positive and negative selection; speciation)

4) Human disease relevance

5) Computational biology aspects (algorithms, databases, websites)

[3] Identify an outstanding research problem and how genomics approaches can be, or are being applied to solve it.

Alternative Project: analyze a gene in depth

[1] Select a single protein, RNA, or DNA sequence. Unless you have a particular gene of interest, select one that is conserved across the three domains of life. Obtain a large number of homologous sequences (e.g. 100) in the fasta format.

[2] Perform a phylogenetic analysis. If your gene is conserved, use the sequence to make a tree of life. If it is protein-coding, analyze the substitution rate at different codon positions, describe ancestral sequences, provide evidence for neutral evolution or selection, etc.

[3] Describe specific cases in which the gene has duplicated (or been lost) across genomes. Provide evidence for duplication/deletion and date the occurrence(s).

[4] Describe conserved synteny for this gene across multiple genomes. Describe its neighboring genes.

[5] Describe regulatory regions controlling expression of this gene.