Notes on Comparative Genomics and Evolution

Comparative genomics provides evidence for evolution and helps establish evolutionary relationships between species.
Key techniques used to infer relationships:
- DNA–DNA hybridisation: denature DNA from two species and allow re-annealing; a higher degree of hybridisation indicates closer relatedness.
- DNA sequencing:
- compare sequences of common proteins (e.g., cytochromes);
- DNA sequencing, including rRNA gene sequencing in prokaryotes.
Phylogenetic trees represent evolutionary relationships and are drawings of hypotheses about relatedness.
Mutations accumulate over time; the mutation rate can be used as a molecular clock.
More closely related species have fewer DNA sequence differences and have diverged more recently from a common ancestor than distantly related species.

DNA is the fundamental chemical of life; it enables cell production and directs protein synthesis.
DNA shows great variety, due to differences in DNA composition across species.
All species use the same four bases (A, T, G, C) and the same coding system, but each species has its own set of DNA and chromosome number/type. $A, T, G, C$ (bases in DNA) with varying chromosome counts per species.

Fossil data can help determine when species first existed and inform evolutionary timelines.

Mutations are random changes to DNA and can be beneficial, harmful, or neutral.
Somatic (body) mutations are not inherited; germline (gamete) mutations can be passed to offspring.
Beneficial mutations are adaptations; harmful mutations may cause genetic diseases.
A single base mutation in one gene is not the sole source of all variation.
Accumulation of point mutations across many genes and populations over time contributes to biodiversity (e.g., saliva gene mutations contributing to venom in snakes).

Molecular clock: compares evolution of biological molecules to estimate when two species diverged from a common ancestor.
Differences in amino acid sequences between species are roughly proportional to divergence time.
Less mutations imply less time since divergence; more mutations imply more time.
Example: if cytochrome c shows $20$ amino acid changes per $100$ residues between two species, divergence time is roughly $5\times 10^8$ years ago.

Sequence comparison uses computer-based analysis to locate differences and regions of similarity.
Example program: Clustal Omega (global multiple sequence alignment for DNA, RNA, and proteins).
Genome comparisons reveal shared ancestry: e.g., about $60\%$ of genes are shared between fruit flies and humans.
Cancer-related human genes have corresponding genes in fruit flies (roughly two-thirds).
The more similar the genetic code, the more closely related the species.

In prokaryotes, the 16S rRNA gene codes for the small ribosomal subunit; in eukaryotes, the 18S rRNA gene codes for the small ribosomal subunit.
Advantages of rRNA sequencing:
- ribosomes are universal; contains both conserved and variable regions, allowing discrimination between species.
- can detect multiple species in a single analysis.
- closely related species have very similar rRNA sequences.

When comparing proteins of the same type (e.g., cytochromes like cytochrome c) from different species, amino acid sequences are compared for differences.
Cytochromes are essential in aerobic respiration and vary among species, reflecting relatedness.

Steps involve comparing DNA from different species to assess similarity.
Example: species with a good DNA–DNA hybridisation match are more closely related than those with a poor match.
This method supports constructing a phylogenetic perspective of relationships among species.

Computer analyses enable large-scale genome comparisons and reveal extensive gene sharing across diverse lineages.
Key takeaway: the degree of genetic similarity correlates with evolutionary relatedness.

16S rRNA (prokaryotes) vs 18S rRNA (eukaryotes) foundation for taxonomic studies.
Clustal Omega as an example of sequence alignment tool.
Conceptual time reference: a divergence example using cytochrome c suggests approximately $5\times 10^8$ years ago.