Evolutionary History Through Genetic Analysis (Lecture 13)

Evolutionary History Through Genetic Analysis

• Genetic analysis reveals evolutionary history without fossils
• Molecular phylogenetic methods and applications are important in understanding evolution
• Selection imprints distinct signatures in DNA sequences
• Coalescence and gene trees provide information to understand evolution

Key Concepts

• Linkage Disequilibrium: Non-random allele association at different loci. Alleles occur more often than predicted
• Coalescence: Tracing genetic lineages to find common allele ancestors
• Incomplete Lineage Sorting: Gene trees mismatch species trees due to ancestral polymorphism
• Selective Sweep: Eliminates genetic variation near a beneficial mutation that has spread
• DnDs Ratio: Compares non-synonymous to synonymous substitution rates to detect selection

Understanding Genetic History Within Species

• Evolutionary history is reconstructed by analyzing current genetic diversity
• DNA is an important marker for phylogenetic analysis
• Individual nucleotide positions act as characters similar to morphological traits
• Genetic data tracks allele paths through populations over time
• Gene trees are constructed through coalescence analysis
• Phylogeny, coalescence, and gene genealogy are important terms

Gene Trees and Coalescence

• Genes possess their own genealogical history traceable through populations
• Multiple alleles can coexist in populations with lineages tracing back through time
• Coalescent events are when lineages merge in a common ancestor
• Gene trees reconstruct historical allele relationships
• Gene trees do not always match species trees due to incomplete lineage sorting
• In the human-chimpanzee-gorilla relationship, around 64% of genes support humans and chimps as sister taxa, while about 18% group humans with gorillas and 18% group chimps with gorillas

Molecular Phylogenetic Methods

• Computational approaches are used to construct evolutionary trees
• Maximum parsimony identifies topology minimizing evolutionary changes
• Distance matrix/Neighbor joining clusters similar sequences based on similarity
• Maximum likelihood determines data probability given evolutionary model
• Bayesian analysis determines tree probability given model and data
• Bootstrap support (confidence measure for branching patterns) and posterior probability (Bayesian confidence measure) are important terms

Case Study - Human Origins

• Molecular phylogenetics support the Out-of-Africa hypothesis
• Two competing hypotheses are multi-regional vs. out-of-Africa models
• Phylogenetic evidence indicates all non-African lineages branch from African clades
• Origin appears near Addis Ababa, Ethiopia
• Genetic diversity decreases with distance from African origin
• Heterozygosity is highest in African populations and lowest in American populations
• Out-of-Africa model, genetic heterozygosity, and human migration patterns are important terms

Neutral Theory and Molecular Clocks

• Most molecular evolution is driven by neutral mutations and genetic drift
• Motoo Kimura (1968) proposed neutral theory of molecular evolution
• Deleterious mutations are purged and neutral mutations fluctuate due to drift
• Molecular evolution rate approximately equals mutation rate
• Linear relationship between genetic differences and time since divergence is evidence
• Molecular clock, neutral theory, and genetic drift are important terms

Types of Mutations and Their Effects

• Different mutations have varying effects on fitness and evolve at different rates
• Synonymous/silent mutations do not change the amino acid sequence and are often neutral
• Non-synonymous mutations change amino acids and are often subject to selection
• Synonymous changes accumulate faster than non-synonymous ones
• Different genomic regions evolve at different rates
• Coding regions evolve slowly (under stronger selection)
• Introns evolve more rapidly (less functionality constrained)
• Intergenic regions evolve even faster (minimal constraint)
• Pseudogenes evolve most rapidly (non-functional)
• Synonymous mutation, non-synonymous mutation, and pseudogene are important terms

Detecting Selection in DNA Sequences

• Selection leaves detectable signatures in DNA sequences
• Selective sweeps eliminate polymorphisms near beneficial mutations
• Hitchhiking occurs when neutral variants linked to beneficial mutations increase in frequency
• DnD ratio reveals different types of selection
  • DnDs > 1: Positive selection (favors amino acid changes)
  • DnDs = 1: Neutral evolution
  • DnDs < 1: Purifying selection (conserves amino acid sequence)
• FST outlier analysis identifies locally adapted regions
• The EPAS1 gene in Tibetans shows positive selection evidence for high-altitude adaptation

Diagrams/Visual Aids

• Gene trees showing coalescence of alleles through time
• Primate phylogeny showing incomplete lineage sorting among humans, chimps, and gorillas
• Map showing correlation between genetic diversity and distance from East Africa
• Charts showing different evolutionary rates in various genetic regions
• Visualizations of selective sweeps and hitchhiking effects

Q&A/Discussion Points

• Linkage disequilibrium is the non-random association between alleles
• New mutations have experienced fewer recombination events, maintaining larger LD blocks
• QTL requires crossing divergent populations, and GWAS uses existing variation in single populations
• Incomplete lineage sorting causes mismatches between gene and species trees, especially when speciation events occur rapidly

Summary/Conclusion

• DNA sequences contain rich information about evolutionary history
• Molecular phylogenetic methods help reconstruct evolutionary relationships
• Human genetic evidence strongly supports African origins
• Most genetic change results from neutral mutations and drift
• Different types of selection leave distinct signatures in DNA sequences
• Adaptation is be detected through DnDs ratios and FST outlier analysis