1. Evolution: Through the Lenses of Protein Sequence and 3D Structure
Shuchismita Dutta, Ph.D.

2. Learning Objectives
Evidences for Evolution
Phylogenetics
Evolution Continues

3. Review Structure of DNA Central Dogma of Biology
Double stranded, base paired
Central Dogma of Biology
DNA  RNA  Protein
Genes, Genomes, Chromosomes
Exons, introns, UTRs
Mitosis
DNA Replication
Meiosis
Special cell division in germ cells
Recombination
This slide provide an opportunity to review the key vocabulary and concepts listed here. Further details about these topics may be found in the following Molecule of the Month features and the genetics learning materials included in the Diabetes Curricular module.
DNA:
Nucleosome:

4. Learning Objectives
Evidences for Evolution
Phylogenetics
Evolution Continues

5. Evidences from Dead Organisms
Fossils
Direct evidences - commonly hard parts e.g. bones, teeth, shells, spores, seeds
Can see morphological similarities or differences between current and ancient life forms
May be used to date when the organism lived
Traces of fossils
Indirect evidences – e.g. footprints, leaf prints, tracks, burrows, tools made/used etc.
Fish Fossil (skeleton); Dennis Hill
Fern Fossil (impression); mjtmail

6. Evidences from Living Organisms
Homologies
Common structures between seen in related species
Biogeography
Species segregated by location (e.g. land mass, body of water)
Embryology
In many species stages of embryo development mimics other organisms

7. Evidences from Molecular Biology
Proteins from all organisms are composed of the same set of 20 amino acids
For example: Hemoglobin and Myoglobin protein structures
Different location/function but similar shape
Tertiary Structure Is More Conserved Than Primary Structure
Similarity of genes/proteins suggests phylogenetic relationship
Hemoglobin a chain
Myoglobin
Leghemoglobin

8. Well Preserved Ancient DNA
Bacterial communities from different layers of the Canadian high Arctic permafrost show
Microbial communities from ~5,000 years ago harbored diverse resistance mechanisms to present day antibiotics!
To learn more read the article:
Perron GG, Whyte L, Turnbaugh PJ, Goordial J, Hanage WP, et al. (2015) Functional Characterization of Bacteria Isolated from Ancient Arctic Soil Exposes Diverse Resistance Mechanisms to Modern Antibiotics. PLoS ONE 10(3): e doi: /journal.pone

9. Learning Objectives
Evidences for Evolution
Phylogenetics
Evolution Continues

10. Phylogenetics Evolutionary relationships of organisms/genes
May be based on
morphological data
Observable characteristics
limb bones etc.
molecular data
DNA and/or protein sequences
Protein structures
Why is it important?
Classification/organization of living world
Forensics
Surveying pathogens
Bioinformatics and computing
This slide emphasizes the importance of phylogenetics. Some of the processes for how this is done is discussed in the next slide.

11. Molecular Phylogenetics Methods
Immunological tests
Proteins from different organisms  recognized by same antibody  organisms exhibiting cross-reactivity are related
Protein electrophoresis
Proteins from different organisms with similar mass/charge ratios are related
Protein sequences
Proteins with similar sequences are related
DNA sequences
Similar DNA sequences from different genes within the same organism  gene duplications
Similar DNA sequences from different genomes  are related
Provide the most detailed and unambiguous data on evolution
Since phylogenetics is based on looking at the similarity of genes and proteins to establish evolutionary relationships there are several ways for determining if the genes are similar and proteins are similar.
Even at the sequence level – the DNA is a more reliable indicator of conservation and evolution. The degeneracy of the genetic code allows for some variations in the DNA sequence still resulting in the same protein sequence and structure. However, comparing DNA sequences would pick up these variations.

12. Evolution of Insulin Family
Insulin and related peptides
Similar in vertebrates and invertebrates
Structure conserved
Organization of propeptide
Cys residues and disulfide bonds
3D structure very similar but invertebrate insulins are monomeric
Function conserved
key regulators of growth and metabolism
Invertebrate insulins are monomeric
Even though invertebrate and human insulins are not very similar in sequence they can bind the insulin receptors
To learn more you may want to read the article listed in the slide as well as
Lecroisey C, et al., (2015). PLoS ONE 10(3): e

13. Learning Objectives
Evidences for Evolution
Phylogenetics
Evolution Continues

14. Ongoing Evolution Examples
Pathogens (e.g. viruses, bacteria, fungi) evolve
To evade the effect of drugs and antimicrobials
Cancer cells evolve
To evade host immune defenses
To resist the effect of pharmaceutical drugs
Plant pests and weeds affecting agricultural/commercial crops evolve
To resist the effects of herbicides and pesticide
Gleevec bound to Abl kinase
(PDB IDs 1iep, 2gqg)
Overlap of Gleevec and Sprycel bound to Abl kinase
(PDB IDs 1iep, 2gqg)

15. Summary
Evidences for Evolution
Phylogenetics
Evolution Continues