Evolutionary Genomics: Genome Structure, Comparative Analysis, and Phenotypic Evolution

Course Announcements and Exam Information

  • Exam 3 Schedule: Thursday, June 11th, from 1:001:00 to 3:00 pm3:00\,pm in the current classroom.
  • Scope: The exam covers five topics discussed since the previous exam. This includes the two topics covered this week but excludes guest lectures on paper topics. It is not a cumulative exam.
  • Format: The exam will follow a similar format and duration as previous assessments.
  • Support: Extra office hours will be posted on Canvas. Review videos are being uploaded as lecture topics are completed.
  • Course Evaluations: Now open at https://eval.ucdavis.edu/.

Evolutionary Genomics Overview

Evolutionary genomics focuses on three primary pillars:

  1. Genome size and organism complexity: Investigating the relationship (or lack thereof) between the size of a genome and the complexity of the organism.
  2. Comparative genomics: Examining genetic variation, conservation in coding and regulatory regions, and chromosome structure to understand evolutionary relatedness.
  3. Phenotypic evolution: Determining how evolved changes in genes lead to changes in physical traits through mechanisms like coding sequence changes, regulatory changes, and the evolution of new genes.

Genome Size and Organism Complexity

  • Genomic Proportions: In many organisms, especially those with large genomes, the proportion of the genome that actually encodes genes is remarkably small.
  • Human Genome Composition: Very little of the human genome consists of exons (1%1\%). The distribution is as follows:     * Exons: 1%1\%     * Introns: 24%24\%     * Transposons (Transposable Elements): 45%45\%     * Other intergenic DNA: 22%22\%     * Simple repeats: 3%3\%     * Large duplications: 5%5\%
  • Repetitive DNA: Eukaryotes vary significantly in their proportion of repetitive DNA. While the human genome is over 50%50\% repetitive, others are even more extreme. For instance, Maize is approximately 90%90\% repetitive DNA.
  • C-Value Paradox: Genome size does not correlate with organismal or morphological complexity. Ranges of genome sizes overlap across different groups (e.g., some protists have larger genomes than humans).
  • Specific Genome Sizes:     * Human genome: ~3 Gbp3\,Gbp (3 billion base pairs3\,billion\,base\,pairs).     * Paris japonica: 150 billion bp150\,billion\,bp (the largest sequenced genome shown).     * South American lungfish: 91 Gbp91\,Gbp.     * Axolotl: 32 Gbp32\,Gbp.
  • Coding Ratio: There is a negative relationship between genome size and the proportion of protein-coding genes. Larger genomes typically have a smaller percentage of protein-coding sequence per MbMb.

Transposable Elements (TEs)

  • Definition: DNA sequences that can move from one location to another within a genome. Often described as "genomic parasites."
  • Impact: Transposition is a form of mutation and can lower the fitness of the host.
  • Types of TEs:     * Autonomous TEs: Code for the enzymes (like transposase) required for their own movement.     * Non-autonomous TEs: Lack the necessary enzymes and must use the machinery provided by autonomous TEs to move.
  • Major Classes:     * DNA Transposons: Utilize a "cut and paste" mechanism. The element is physically cut from one chromosome location and reintegrated elsewhere via the transposase enzyme. They feature Terminal Inverted Repeats (TIR).     * Retrotransposons: Utilize a "copy and paste" mechanism involving an RNA intermediate. mRNA is transcribed by RNA Pol II, converted to cDNA by reverse transcriptase, and integrated into a new position by an integrase enzyme. They often feature Long Terminal Repeats (LTR).
  • Human Examples:     * L1: Autonomous retrotransposons (850,000850,000 copies).     * Alu: Non-autonomous retrotransposons (1 million1\,million copies).     * LTR retrotransposons: Related to retroviruses (230,000230,000 copies).     * Activity: Almost all TEs in the human genome are now inactive. Rare active insertions occur at a rate of approximately one per 1010 to 100100 live births.
  • Source of Variation: TEs cause mutations associated with human diseases (e.g., Hemophilia A/B, Cystic Fibrosis, Duchenne Muscular Dystrophy). However, they can provide beneficial variation, such as the evolution of the placenta and many of Mendel's original pea plant mutations.

Comparative Genomics and Conservation

  • Phylogenetics: The study of evolutionary history and relationships using shared ancestry. Phylogenies (diagrams) represent these relationships.
  • Homologous Nucleotides: Nucleotides descended from the same position in a common ancestor. Sequence alignment allows scientists to count changes. Fewer changes between species indicate a more recent common ancestor.
  • Sequence Conservation: Investigating how sequences remain unchanged over time reveals function.     * Evolutionary Constraint: Sequences with vital functions are under high constraint; mutations in these regions are usually removed by natural selection.     * Peaks of conservation in alignments typically correspond to exons or Conserved Noncoding Sequences (CNS).
  • Degeneracy and Constraint: Functional constraint varies even within coding regions.     * Fourfold degenerate sites: Sites where any of the four nucleotides (A, T, G, C) results in the same amino acid (e.g., the third position of Proline codons: CCC, CCG, CCA, CCU). These evolve faster than non-degenerate sites.
  • Regulatory Prediction: Highly conserved non-coding regions likely contain critical cis-regulatory elements like promoters, enhancers, or silencers. For example, comparing the Pax-7 non-coding region across humans, dogs, mice, chickens, and fish helps identify important enhancers.

Synteny: Conservation of Gene Order

  • Definition: The conserved order of consecutive genes along a chromosome segment between different species.
  • Applications:     * Understanding chromosomal evolution.     * Identifying new genes or gene duplications/whole-genome duplications.     * Example: Human Chromosome 2121 shows synteny with segments of Mouse Chromosomes 1616, 1717, and 1010.

Mechanisms of Phenotypic Evolution

New phenotypes evolve through three primary modes:

  1. Changes in Coding Sequence: Altering the amino acid sequence of a protein.
  2. Changes in Gene Regulation: Altering where or when a gene is expressed (temporal or spatial changes).
  3. Evolution of New Genes: Creating novel genetic material.
Case Study: Flower Color in Mimulus
  • Phenotype: Mimulus lewisii has pink flowers, while variants can be white.
  • Mechanism: A 2 bp2\,bp insertion in the DFR (Dihydroflavonol 4-reductase) gene sequence creates a frameshift.
  • Result: This leads to a loss of function in the anthocyanin biosynthetic pathway. The change is in the coding region, as cross-breeding shows it segregates as a single recessive locus and gene expression levels remain unchanged.
Case Study: Stickleback Armour Evolution
  • Phenotype: Marine sticklebacks have pelvic spines and girdle for protection against gape-feeding predators. Freshwater populations have repeatedly lost these spines to move faster and avoid freshwater predators.
  • Mechanism: A QTL (Quantitative Trait Loci) study identified the Pitx1 gene.
  • Finding: There is no change in the Pitx1 protein-coding region. Instead, Pitx1 expression is lost specifically in the pelvic region of freshwater fish.
  • Regulatory Evidence: The expression change is due to a mutation in a tissue-specific enhancer. When freshwater fish are injected with a construct containing the marine enhancer driving Pitx1, they develop pelvic spines.

The Birth of New Genes: Gene Duplication

  • Orthologs: Genes in different species derived from a single ancestral gene in the last common ancestor.
  • Paralogs: Similar genes created by a duplication event within a genome.
  • Mechanisms of Duplication:     * Unequal Crossing Over: Occurs between homologs during meiosis, often resulting in tandem duplicates (genes located next to each other).     * Retrotransposition: mRNA is reverse-transcribed and the DNA copy is inserted elsewhere. These copies lack introns and may have a poly-A tail (e.g., Chondrodysplasia in dogs caused by a retrotransposed fgf4 gene).
  • Hox Genes: Diversity in Hox genes (critical for body patterning) arose through tandem duplications and genome tetraploidization events.
Fates of Duplicated Genes

Most duplications are lost or become deleterious (e.g., HIV susceptibility, color blindness, cancers). If they persist, they diverge through:

  1. Subfunctionalization: Each paralog maintains a different, complementary subset of the original gene's functions.
  2. Neofunctionalization: One paralog maintains the ancestral function while the other evolves a entirely new function.
  3. Pseudogenization (Degeneration): The duplicate accumulates mutations and becomes non-functional (the most frequent outcome).
Evolution of Primate Color Vision
  • Humans: Trichromatic vision with three cone opsins: SWS (417 nm417\,nm, blue), MWS (530 nm530\,nm, green), and LWS (560 nm560\,nm, red).
  • Mechanism: In Old World Monkeys/Apes, the Green opsin gene duplicated and diverged into the Red opsin approximately 30 MYA30\,MYA.
  • Amino Acid Shifts: Changes at positions 180180, 277277, and 285285 caused the spectral shifts (3−4 nm3-4\,nm, 7 nm7\,nm, and 14 nm14\,nm respectively).
  • Convergent Evolution: Howler Monkeys independently evolved trichromatic vision 5 MYA5\,MYA using the exact same amino acid changes through neofunctionalization.