12  Comparative Genomics and Evolution

12.1 Comparing Genomes to Understand Life

12.1.1 What Is Comparative Genomics?

Comparative genomics = Comparing genomes from different species to understand:

  • How we’re related

  • How we evolved

  • What makes each species unique

  • Which genes are important

Think of it like:

  • Comparing different recipes to see what’s essential

  • Looking at different car models to understand basic car design

  • Studying different languages to find common roots

12.2 Why Compare Genomes?

12.2.1 What We Learn

1. Evolutionary Relationships

  • Which species are closely related?

  • When did species diverge?

  • How did we evolve from common ancestors?

2. Gene Function

  • Genes conserved across species are probably important!

  • If mice and humans share a gene, it must be essential

  • Can study gene function in simple organisms

3. Human Health

  • Understand genetic diseases

  • Why some species don’t get certain diseases

  • Identify drug targets

4. Conservation

  • Genetic diversity in endangered species

  • Evolutionary distinctiveness

  • Guide conservation efforts

12.3 The Tree of Life

12.3.3 What the Numbers Mean

High similarity doesn’t mean we’re the same!

  • That small % difference creates huge changes

  • Gene regulation matters as much as genes themselves

  • Timing and location of gene expression crucial

Example - Humans vs Chimpanzees:

  • 98% similar genomes

  • But very different!

  • Differences in:

    • Brain size and structure

    • Language ability

    • Bipedal walking

    • Reduced body hair

    • Longer lifespan

12.4 Conserved Genes and Sequences

12.4.1 What’s Been Preserved Through Evolution?

Conserved sequences = DNA/protein sequences that haven’t changed much over millions of years

Why conserve?

  • If it works, don’t change it!

  • Changes would be harmful

  • Under “purifying selection” (bad changes eliminated)

12.4.2 Highly Conserved Genes

Housekeeping genes:

  • Needed by all cells

  • Basic cellular functions

  • DNA replication, transcription, translation

  • Energy production

Example - Histones:

  • DNA packaging proteins

  • Nearly identical from yeast to humans

  • Changed very little in 1 billion years!

Example - Ribosomal RNA:

  • Used to build ribosomes

  • Extremely conserved

  • Used to construct tree of life!

12.4.3 Ultraconserved Elements

Ultraconserved elements = DNA sequences 100% identical across species

Mind-blowing fact:

  • Some sequences are EXACTLY the same in humans, mice, rats

  • Over 200 base pairs long

  • Separated by ~75 million years of evolution

  • Must be VERY important!

What do they do?

  • Many are enhancers (regulate genes)

  • Control development

  • We’re still figuring it out!

12.5 Synteny: Gene Order Conservation

12.5.1 Genes Stay Together

Synteny = Genes located in the same order on chromosomes across species

Example:

  • Human chromosome 1 has genes A-B-C-D-E

  • Mouse chromosome 2 might have genes A-B-C-D-E in same order

  • Shows common ancestry!

Why it matters:

  • Helps identify corresponding genes across species

  • Understanding chromosome evolution

  • Clues about gene function

Exceptions:

  • Chromosomal rearrangements happen

  • Inversions, translocations

  • Create differences between species

12.6 Molecular Clocks

12.6.1 Dating Evolution with DNA

Molecular clock = Using mutation rate to estimate when species diverged

The concept:

  • Mutations accumulate over time

  • At roughly constant rate

  • More differences = longer time since common ancestor

How it works:

  1. Compare DNA sequences between two species

  2. Count differences

  3. Know mutation rate

  4. Calculate time since divergence

Example:

  • Humans and chimps differ by ~35 million base pairs

  • Mutation rate ~ 1 change per billion bases per year

  • Estimate divergence: 5-7 million years ago

  • Matches fossil evidence!

12.6.2 Calibrating the Clock

Problems:

  • Mutation rates aren’t perfectly constant

  • Vary between species

  • Vary across genome

Solution:

  • Use fossil evidence to calibrate

  • Known divergence dates from fossils

  • Adjust molecular clock accordingly

12.7 Gene Families and Evolution

12.7.1 Genes Evolve by Duplication

Gene families = Groups of related genes from a common ancestor

How they form:

  1. Gene duplicates (DNA copying error)

  2. Now two copies of same gene

  3. One copy can mutate freely

  4. Diverge to perform new or specialized functions

12.7.2 Types of Gene Relationships

Orthologs:

  • Same gene in different species

  • Separated by speciation

  • Usually same function

  • Example: Human insulin vs. mouse insulin

Paralogs:

  • Related genes within same genome

  • Separated by duplication

  • Often different functions

  • Example: α-globin vs. β-globin (both in hemoglobin)

12.7.3 Example: Globin Gene Family

The story:

  • Ancient globin gene

  • Duplicated many times

  • Diverged into specialized forms

  • Myoglobin (stores oxygen in muscle)

  • Hemoglobin α and β chains (transport oxygen in blood)

  • Fetal hemoglobin (binds oxygen better than adult form)

Cool fact: All from one ancestral gene!

12.8 What Makes Humans Human?

12.8.1 The 2% Difference

Humans and chimps share 98% of DNA. What accounts for the 2%?

Key differences:

1. FOXP2 Gene:

  • Transcription factor

  • Important for language and speech

  • Humans have 2 amino acid changes vs. chimps

  • Linked to speech development

2. HAR1 (Human Accelerated Region 1):

  • Rapidly evolved in humans

  • Involved in brain development

  • Controls cortex formation

  • Only 18 changes but huge impact!

3. Gene Regulation Changes:

  • Not just which genes, but WHEN and WHERE

  • Brain genes expressed more in humans

  • Different expression patterns during development

4. Copy Number Variations:

  • Humans have more copies of some genes

  • Salivary amylase (digests starch) - varies by diet

  • Brain development genes - duplications

5. Lost Genes:

  • Humans LOST some genes chimps have

  • Loss of jaw muscle gene → bigger brain case

  • Loss of spine genes → smoother skin

12.9 Evo-Devo: Evolution Meets Development

12.9.1 How Body Plans Evolve

Evo-Devo = Evolutionary developmental biology

Key insight: Changes in development genes create new body forms

Hox Genes Across Animals:

  • ALL animals have Hox genes!

  • Control body plan (head to tail)

  • Same genes in flies, fish, mice, humans

  • Different regulation = different bodies

Example - Snakes:

  • Have Hox genes like mice

  • But expressed differently

  • Extended body region

  • No limbs (limb genes repressed)

Example - Giraffe Neck:

  • Same number of neck bones as mice (7)

  • But each vertebra is much longer

  • Changed growth regulation, not genes themselves!

12.10 Genomic Islands and Hotspots

12.10.1 Regions of Rapid Evolution

Genomic islands:

  • Regions that evolve faster than average

  • Often involved in adaptation

  • Species-specific traits

Examples:

  • Immune system genes (pathogen arms race)

  • Sensory genes (different environments)

  • Reproductive genes (sexual selection)

12.11 Ancient DNA and Extinct Species

12.11.1 Learning from the Past

Paleogenomics = Sequencing DNA from extinct species

Success stories:

1. Neanderthals:

  • Sequenced whole genome

  • Interbred with humans

  • 1-4% of non-African human DNA is Neanderthal

  • Contributed immunity genes

2. Denisovans:

  • Known only from DNA (and few bones)

  • Interbred with humans

  • Contributed high-altitude adaptation genes (Tibetans)

3. Woolly Mammoths:

  • Sequenced from frozen specimens

  • Understanding adaptation to cold

  • De-extinction efforts underway!

4. Ancient Humans:

  • Track human migrations out of Africa

  • Understand population history

  • Admixture events

12.12 Horizontal Gene Transfer

12.12.1 Genes Jump Between Species!

Horizontal gene transfer (HGT) = Genes transferred between species (not parent to offspring)

Common in bacteria:

  • Antibiotic resistance genes spread this way

  • Public health concern!

Also in eukaryotes:

  • Bdelloid rotifers: 8% of genes from bacteria, fungi, plants!

  • Aphids: Got bacterial genes for making pigments

  • Tardigrades: Extreme survival partly from borrowed genes

Implications:

  • Tree of life is more like a web

  • Evolution more complex than thought

  • Challenges traditional classification

12.13 Applications of Comparative Genomics

12.13.1 Practical Uses

1. Medicine:

  • Model organisms (mice, zebrafish, flies)

  • Test genes in simple organisms

  • Understand human disease genes

  • Predict drug targets

2. Agriculture:

  • Compare crop genomes

  • Find genes for drought tolerance, disease resistance

  • Breed better crops

  • Understand domestication

3. Conservation:

  • Genetic diversity assessments

  • Identify unique populations

  • Guide breeding programs

  • Prioritize species for protection

4. Biotechnology:

  • Find useful genes in other organisms

  • Extremophiles (heat, cold, acid tolerance)

  • Industrial enzymes

  • Bioremediation

12.14 The Genome as a History Book

12.14.1 Reading Our Past

Genomes contain records of:

  • Ancient viral infections (endogenous retroviruses)

  • Gene duplications

  • Chromosomal rearrangements

  • Population bottlenecks

  • Admixture events

  • Selective pressures

It’s like archaeology:

  • Digging through layers of time

  • Finding ancient “artifacts” (sequences)

  • Reconstructing the past

12.15 Key Takeaways

  • Comparative genomics compares genomes across species

  • All life is related - shares common ancestor

  • Conserved sequences indicate important functions

  • Molecular clocks date evolutionary events using mutation rates

  • Gene families evolve through duplication and divergence

  • Orthologs = same gene in different species

  • Paralogs = related genes in same species

  • Small genetic changes can have huge effects (regulation matters!)

  • Evo-devo explains how development changes create new forms

  • Ancient DNA reveals history of extinct species and human evolution

  • Horizontal gene transfer shows evolution is complex

  • Comparative genomics has practical applications in medicine, agriculture, conservation

Sources: Information adapted from comparative genomics research, evolutionary biology literature, and ancient DNA studies.