Transcript Evolution - RCSB PDB

Evolution: Through the Lenses of Protein
Sequence and 3D Structure
Shuchismita Dutta, Ph.D.
Learning Objectives
• Evidences for Evolution
• Phylogenetics
• Evolution Continues
Developed as part of the RCSB Collaborative Curriculum Development Program 2016
Review
• Structure of DNA
• 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
Developed as part of the RCSB Collaborative Curriculum Development Program 2016
Learning Objectives
• Evidences for Evolution
• Phylogenetics
• Evolution Continues
Developed as part of the RCSB Collaborative Curriculum Development Program 2016
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
Fish Fossil (skeleton); Dennis Hill
– 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.
Fern Fossil (impression); mjtmail
http://www.photosforclass.com/;
http://creativecommons.org/licenses/by/2.0/#sthash.nBGYc3wJ.dpuf
Developed as part of the RCSB Collaborative Curriculum Development Program 2016
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
Developed as part of the RCSB Collaborative Curriculum Development Program 2016
https://www.ncbi.nlm.nih.
gov/books/NBK230201/fig
ure/mmm00013/?report=
objectonly
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
https://www.ncbi.nlm.nih.gov/books/NBK22362/figure/A946
Developed as part of the RCSB Collaborative Curriculum Development Program 2016
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!
http://journals.plos.org/plosone/article?id=info:doi/10.1371/journal.
pone.0069533
Developed as part of the RCSB Collaborative Curriculum Development Program 2016
Learning Objectives
• Evidences for Evolution
• Phylogenetics
• Evolution Continues
Developed as part of the RCSB Collaborative Curriculum Development Program 2016
Phylogenetics
• Evolutionary
relationships of
organisms/genes
• May be based on
– morphological data
• Observable
characteristics
• limb bones etc.
• Why is it important?
– Classification/organizatio
n of living world
– Forensics
– Surveying pathogens
– Bioinformatics and
computing
– molecular data
• DNA and/or protein
sequences
• Protein structures
Developed as part of the RCSB Collaborative Curriculum Development Program 2016
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
Developed as part of the RCSB Collaborative Curriculum Development Program 2016
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
Lecroisey C, et al., (2015). PLoS ONE 10(3): e0119461.
Developed as part of the RCSB Collaborative Curriculum Development Program 2016
Learning Objectives
• Evidences for Evolution
• Phylogenetics
• Evolution Continues
Developed as part of the RCSB Collaborative Curriculum Development Program 2016
Ongoing Evolution Examples
• Pathogens (e.g. viruses,
bacteria, fungi) evolve
– To evade the effect of drugs
and antimicrobials
Gleevec bound to Abl kinase
(PDB IDs 1iep, 2gqg)
• 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
T315I
GLEEVEC
F317L
SPRYCEL
Activation Loop
Phosphate Binding Loop
Overlap of Gleevec and Sprycel bound to Abl kinase
(PDB IDs 1iep, 2gqg)
Developed as part of the RCSB Collaborative Curriculum Development Program 2016
Summary
• Evidences for Evolution
• Phylogenetics
• Evolution Continues
Developed as part of the RCSB Collaborative Curriculum Development Program 2016