2/20/25

Candidata Phylogenetic Concepts and Methods: This section will cover the essential principles of phylogenetics, including tree-building methods, molecular data analysis, and the interpretation of phylogenetic trees in evolutionary biology.

Learning Objectives

• Understand the molecular clock and its use in dating branching events in phylogenies.

• Analyze dated phylogenies to understand significant events in the diversification of life.

• Explore the structure of the Tree of Life using advanced phylogenetic methods.

Darwin's Hypothesis

• Investigation into the role of natural selection and adaptation in the origin of new species.

Detecting Positive Selection

Key Questions

• How can we identify positive selection and adaptation in the evolutionary divergence of species, especially without knowledge of traits under selection?

Method of Comparison

• Compare DNA sequences of two species to identify a genomic signature of positive selection.

Analysis of Homologous Genes

• Examine substitutions in homologous genes and assess whether natural selection influenced these changes.

• Null Hypothesis: Assumes genetic drift is responsible for substitutions rather than natural selection.

• Testing involves statistical methods to compare observed data against the null hypothesis.

Example: Gene Sequence Comparison

• Comparison between two species shows:

  • Val->Thr->Pro->Glu->Glu->Lys->Ser (one species)

  • Val->Thr->Pro->Val->Glu->Lys->Ser (another species)

• Mutations can be classified as nonsynonymous (changing amino acid sequence) or synonymous (no change).

Effects of Selection on Genes

• Nonsynonymous mutations can either:

  • Be deleterious, eliminated by purifying selection.

  • Be beneficial, spread through positive selection.

Ka/Ks (dN/dS) Test of Selection

Overview

• Examines the ratio of nonsynonymous substitutions per nonsynonymous site (Ka) versus synonymous substitutions per synonymous site (Ks).

Expectations

• Typically, Ka < Ks due to the removal of deleterious nonsynonymous mutations by purifying selection.

Indications of Positive Selection

• If Ka > Ks, this indicates that positive selection may be acting on the gene, leading to an excess of nonsynonymous substitutions.

Interpreting Ka/Ks Ratios

Table of Nature of Selection

• Purifying Selection: Ka/Ks < 1

• Near Neutrality: Ka/Ks = 1

• Positive Selection: Ka/Ks > 1

Case Study

• Hawaiian Silversword Group: Comparison of Ka/Ks ratios for two regulatory genes among species.

Recap on Divergence and Positive Selection

• Lack of positive selection implies many substitutions are synonymous, with deleterious mutations eliminated by purifying selection.

• An excess of nonsynonymous substitutions supports positive selection and suggests the Ka/Ks test as a robust comparison tool.

Ecological Opportunities and Adaptive Radiations

• Ecological changes can spur adaptive radiations.

• Require dating diversification events alongside environmental history to identify such opportunities.

The Molecular Clock Discovery

• Pioneers: Motoo Kimura and Tomoko Ohta.

Nucleotide Differences

• Data indicates a correlation between nucleotide differences and divergence time among virus strains.

Rate of Substitutions

• Understanding how the rate of synonymous substitutions evolves over time

  • Options: A. Increases with time, B. Constant, C. Decreases with time.

Fossil and Sequence Data in Evolution

• Integrate fossil data to reconstruct evolutionary history:

  • Interpretation of ages based on sequence data tracking the evolution of different clades.

Recap on Findings

• Constant substitution rate is characteristic of a clade, used to define a clade's molecular clock.

• Calibrated molecular clocks can date branching events, as seen in the Cambrian explosion, indicating diversification predating fossil evidence by 100 million years.

The Tree of Life Insights

• Introduction to the Tree of Life, revealing three domains: Archaea, Bacteria, and Eukarya.

• Findings based on 16S rRNA, emphasizing the conservation of this sequence among organisms.

Recent Tree Reconstruction

• Utilization of high-quality whole genomes (3,083) and metagenomics data to reconstruct a modern Tree of Life (Hug et al. 2016).

Biodiversity Insights

• Many life forms exist without isolated representatives, typically as symbionts characterized by reduced genomes and metabolic functions.

Final Recap on Key Concepts

• Ka/Ks Test: Tool to detect positive selection driving evolutionary changes.

• Molecular Clock: Constant accumulation of synonymous substitutions useful in dating evolutionary events.

• Tree of Life: Insights into biodiversity, emphasizing lineages lacking isolated representatives, often being symbiotic with small genomes.