Transcript Genetic Research Lesson 3

LESSON 3:
Using Bioinformatics to Study Evolutionary Relationships
PowerPoint slides to accompany
Using Bioinformatics:
Genetic Research
Chowning, J., Kovarik, D., Porter, S., Grisworld, J., Spitze, J., Farris, C., K. Petersen, and T.
Caraballo. Using Bioinformatics: Genetic Research. Published Online October 2012. figshare.
http://dx.doi.org/10.6084/m9.figshare.936568
Microbiologist
Lalita Ramakrishnan, MD, PhD
Place of Employment:
University of Washington
Type of Research:
Tuberculosis infection
Model Organism:
Zebrafish
Zebrafish are naturally susceptible to
tuberculosis. Because their genes are fairly
easy to manipulate, we can create some
zebrafish that are susceptible to TB and some
that are resistant to TB. Zebrafish are also good
model organisms because they are transparent,
so we can watch the infection process develop.
Comparing DNA Sequences
Example: Genetic Testing using BLAST
Reference BRCA1 Sequence A T A G C T G
Query Sequence(s): Patient 1 A
Patient 2 A
C
Patient 3
Look for mutations or changes
relative to Reference Sequence
Comparing DNA Sequences
Example: Genetic Testing using BLAST
Reference BRCA1 Sequence A T A G C T G
Query Sequence(s): Patient 1 A
C
Patient 2 A
Look for mutations or changes
relative to Reference Sequence
Patient 3
Example: Multiple Sequence Alignments
Using JalView and ClustalW
Papaya
Grape
Tomato
Watermelon
ATG GTG C
ATG CTG C
ATG CA G C
ATG G ACA
Look for changes
relative to each other
The amount of change among the sequences reflects
the evolutionary relatedness of the organisms.
Image Source: Wikimedia Commons.
Pairs of Sequences are Compared to Each Other
Papaya: ATGGTGCCG
Grape: ATGCTGCCG
Grape :
ATGCTGCCG
Watermelon: ATGGACACG
Grape : ATGGTGCCG
Tomato: ATGGTGAAG
Papaya : ATGGTGCCG
Tomato: ATGCAGCCG
Tomato :
ATGCAGCCG
Watermelon: ATGGACACG
Papaya:
ATGGTGCCG
Watermelon: ATGGACACG
Number of Nucleotide Differences:
Papaya
Grape
Tomato
Watermelon
Papaya
0
1
2
3
Image Source: Wikimedia Commons.
Grape
1
0
2
4
Tomato
2
2
0
3
Watermelon
3
4
3
0
Phylogenetic Trees Reflect Evolution
External Nodes
Internal Nodes
(Common Ancestors)
Image Source: Wikimedia Commons.
Phylogenetic Trees: The Carnivores
Relatedness of Major Carnivores
Cats
Cat Branch
Domestic Cat
Felis catus
Civets
Mongooses
Hyenas
Spotted Hyena
Crocuta crocuta
Canids
Internal Nodes
(Common Ancestors)
Bears
Dog/Bear
Branch
Red Pandas
Skunks
Weasels
Raccoons
Seals
Fur Seals
Sea Lions
Walruses
Gray Wolf
Canis lupus
Raccoon
Procyon lotor
Adapted from : “WhoZoo: Images and Information about Animals at the Fort Worth Zoo.”
http://www.whozoo.org/mammals/Carnivores/carnivorephylogeny.htm. Developed in part from mitochondrial sequence data from Arnason, et al.
Mammalian mitogenomic relationships and the root of the eutherian tree. PNAS 99 (June 11, 2002): 8151-8156.
Images Source includes Wikimedia Commons.
Phylogenetic Trees: Infectious Disease
Pandemic H1N1 Influenza (“bird flu”)
Internal Nodes
(Common Ancestors)
Pandemic H1N1 2009
‘Spanish Flu’ H1N1 1918
California/7/2009
California/4/2009
Mexico/4/2009
New York/1/1918
South Carolina/1/1918
Puerto Rico/8/1934
Denver/1/1957
Brisbane/57/2007
Solomon Islands/3/2006
New Caledonia/20/1999
Scale:
‘Seasonal Flu’ H1N1
0.08% different
Adapted from: Zimmerman SM, Crevar CJ, Carter DM, Stark JH, Giles BM, et al. (2010). Seroprevalence Following the Second
Wave of Pandemic 2009 H1N1 Influenza in Pittsburgh, PA, USA. PLoS ONE 5(7): e11601. doi:10.1371/journal.pone.0011601.
Influenza Image Source: Wikimedia Commons.
Phylogenetic Trees with an Outgroup
Provide a Point of Reference
Outgroup:
Laminaria
(brown algae)
Tomato
Grape
Papaya
Watermelon
Image Source: Wikimedia Commons.
Microbiologist
Lalita Ramakrishnan, MD, PhD
Place of Employment:
University of Washington
Type of Research:
Tuberculosis infection
Model Organism:
Zebrafish
Zebrafish are naturally susceptible to
tuberculosis. Because their genes are fairly
easy to manipulate, we can create some
zebrafish that are susceptible to TB and some
that are resistant to TB. Zebrafish are also good
model organisms because they are transparent,
so we can watch the infection process develop.
CAREERS IN SPOTLIGHT:
Microbiologist
What do they do?
Microbiologists study microbes: bacteria, viruses, fungi, and protists.
Dr. Ramakrishnan is an expert in tuberculosis, a type of bacteria that infects
almost a third of humanity worldwide. She also studies immunology, including
the body’s reaction to or defense from microbes.
What kind of training is involved?
Most Microbiologists who run their own lab have a Bachelor’s degree and a
PhD (which is usually 5–6 years of research training). However, each lab often
employs scientists with diverse backgrounds, including people with Associate’s,
Bachelor’s, and Master’s degrees.
What is a typical salary for a Microbiologist?
Associate’s degree: $35,000/year ($17.50/hour)
PhD, Full Professor: $100,000/year or more ($48.00/hour)
Source: Bureau of Labor and Statistics