7.1 Molecular evolution and selection

Molecular evolution explores how genetic sequences change over time through mutations, selection, and genetic drift. These processes shape the patterns we see in DNA and proteins across species. Understanding molecular evolution helps us uncover the forces driving genetic diversity and adaptation.

This topic dives into different types of selection and their effects on genetic variation. We'll learn about positive, purifying, balancing, and directional selection, and how to spot their signatures in molecular data. We'll also explore the neutral theory and its implications for interpreting genetic patterns.

Molecular Evolution Principles

Genetic Variation and Molecular Evolution

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• Molecular evolution refers to the process by which genetic sequences change over time due to mutations, selection, and genetic drift
• Mutations are the ultimate source of genetic variation can be caused by errors in DNA replication, exposure to mutagens, or other factors
  • Point mutations involve single nucleotide changes (substitutions)
  • Insertions add one or more nucleotides to a sequence
  • Deletions remove one or more nucleotides from a sequence
  • Duplications create additional copies of a genetic region
• Selection acts on genetic variation, favoring beneficial mutations and removing deleterious ones, thus shaping the patterns of molecular evolution
• Genetic drift is the random fluctuation in allele frequencies due to sampling effects in finite populations can lead to the fixation or loss of alleles
  • Smaller populations are more susceptible to genetic drift
  • Genetic drift can cause non-adaptive changes in allele frequencies

Interplay of Evolutionary Forces

• The interplay between mutation, selection, and genetic drift determines the rate and patterns of molecular evolution in different genomic regions and species
• Mutation introduces new genetic variation, while selection and drift shape the fate of these variants
• Selection tends to favor adaptive changes and remove deleterious ones
• Genetic drift can lead to random changes in allele frequencies, particularly in small populations
• The relative importance of selection and drift varies across genomic regions and species
  • Highly conserved regions (essential genes) are typically under strong purifying selection
  • Rapidly evolving regions (viral surface proteins) may experience positive selection
  • Neutral regions (pseudogenes) are primarily affected by genetic drift

Selection Types and Effects

Positive and Purifying Selection

• Positive selection occurs when a mutation confers a fitness advantage and increases in frequency in the population leading to the fixation of the beneficial allele
  • Examples include mutations that confer resistance to antibiotics or herbicides
  • Positive selection can lead to rapid evolutionary changes in response to environmental pressures
• Purifying (negative) selection removes deleterious mutations from the population, maintaining the functionality and stability of molecular sequences
  • Most nonsynonymous mutations are deleterious and subject to purifying selection
  • Purifying selection conserves the amino acid sequence of proteins and maintains their function

Balancing and Directional Selection

• Balancing selection maintains multiple alleles in a population, often due to heterozygote advantage or frequency-dependent selection
  • Heterozygote advantage (sickle cell anemia and malaria resistance)
  • Frequency-dependent selection (rare alleles favored, common alleles disadvantaged)
• Directional selection favors extreme phenotypes and can lead to rapid changes in allele frequencies and the fixation of advantageous alleles
  • Artificial selection in domesticated species (increased milk production in dairy cows)
  • Natural selection for adaptive traits (beak size in Galápagos finches)
• Stabilizing selection favors intermediate phenotypes and reduces genetic variation, maintaining the status quo in a population
  • Selection for optimal birth weight in humans
  • Selection for intermediate flowering time in plants

Inferring Selection from Molecular Data

• The type and strength of selection acting on a molecular sequence can be inferred from the patterns of genetic variation and the ratio of nonsynonymous to synonymous substitutions (dN/dS ratio)
• A dN/dS ratio > 1 indicates positive selection, as nonsynonymous mutations are favored
• A dN/dS ratio < 1 suggests purifying selection, as nonsynonymous mutations are removed
• A dN/dS ratio ≈ 1 is consistent with neutral evolution, where nonsynonymous and synonymous mutations accumulate at similar rates

Neutral Theory and Implications

Neutral Theory Principles

• The neutral theory of molecular evolution proposes that most genetic variation at the molecular level is selectively neutral and shaped by random genetic drift rather than selection
• Neutral mutations do not affect the fitness of an organism and are not subject to selection, allowing them to accumulate over time
• The rate of neutral molecular evolution is determined by the mutation rate and the effective population size, as described by the molecular clock hypothesis
  • Molecular clock: the rate of molecular evolution is relatively constant over time
  • Allows the estimation of divergence times between species or populations

Implications of Neutral Theory

• The neutral theory explains the observed patterns of genetic variation, such as the preponderance of low-frequency alleles and the relationship between genetic diversity and effective population size
• Larger populations are expected to have higher levels of genetic diversity under neutrality
• The neutral theory provides a null model for detecting signatures of selection
  • Deviations from neutral expectations can indicate the action of selection
• While the neutral theory emphasizes the role of genetic drift, it does not exclude the importance of selection in shaping molecular evolution, particularly for adaptive or deleterious mutations
• The neutral theory has been influential in shaping our understanding of molecular evolution and has provided a framework for interpreting genetic variation

Molecular Evolution Patterns

Sequence Alignment and Phylogenetic Analysis

• Sequence alignment is a fundamental step in analyzing molecular evolution, allowing the comparison of homologous sequences and the identification of conserved and variable regions
  • Pairwise alignment compares two sequences
  • Multiple sequence alignment compares three or more sequences
  • Alignments can reveal conserved functional domains and evolutionary relationships
• Phylogenetic trees are used to represent the evolutionary relationships among sequences can be inferred using various methods, such as maximum parsimony, maximum likelihood, and Bayesian inference
  • Maximum parsimony: minimizes the number of evolutionary changes required
  • Maximum likelihood: identifies the tree that maximizes the probability of observing the data
  • Bayesian inference: incorporates prior knowledge and calculates posterior probabilities
• The branch lengths of phylogenetic trees represent the amount of evolutionary change (number of substitutions) along each lineage can be used to estimate evolutionary rates and divergence times

Statistical Tests for Selection

• Statistical tests, such as the McDonald-Kreitman test and the Hudson-Kreitman-Aguadé test, can be used to detect signatures of selection by comparing the patterns of polymorphism and divergence
• The McDonald-Kreitman test compares the ratio of nonsynonymous to synonymous substitutions within and between species
  • An excess of nonsynonymous substitutions between species suggests positive selection
• The Hudson-Kreitman-Aguadé test compares the levels of polymorphism and divergence in a target region to a neutral reference region
  • Reduced polymorphism and increased divergence in the target region indicates positive selection
• The dN/dS ratio, which compares the rates of nonsynonymous and synonymous substitutions, can be used to infer the type and strength of selection acting on protein-coding sequences
  • Different codon models can be used to estimate dN/dS ratios across sites or lineages

Ancestral Sequence Reconstruction

• Ancestral sequence reconstruction methods allow the inference of the most likely ancestral states of molecular sequences at internal nodes of a phylogenetic tree, providing insights into the evolutionary history of specific mutations or traits
• Maximum likelihood and Bayesian methods are commonly used for ancestral sequence reconstruction
• Reconstructed ancestral sequences can be used to study the functional evolution of proteins, identify key adaptive mutations, and trace the evolutionary history of specific traits
  • Reconstructing the ancestral hemoglobin sequence in vertebrates
  • Identifying adaptive mutations in the evolution of antibiotic resistance
• Ancestral sequence reconstruction is subject to statistical uncertainties and depends on the accuracy of the phylogenetic tree and the models of molecular evolution used