LESSON 3: Using Bioinformatics to Study Evolutionary Relationships

PowerPoint slides to accompany

Using Bioinformatics: Genetic Research

MicrobiologistLalita 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

Reference BRCA1 Sequence Query Sequence(s): Patient 1 Look for mutations or changes

relative to Reference SequenceAA

C

A T A G C T G

Example: Genetic Testing using BLAST

Patient 2

Patient 3

Comparing DNA Sequences

Example: Genetic Testing using BLAST

Example: Multiple Sequence Alignments Using JalView and ClustalW

The amount of change among the sequences reflects the evolutionary relatedness of the organisms.

TomatoWatermelon

PapayaGrape Look for changes

relative to each other

A T G G T G CA T G C T G CA T G C A G CA T G G A C A

Reference BRCA1 Sequence Query Sequence(s): Patient 1 Look for mutations or changes

relative to Reference SequenceAA

C

A T A G C T G

Patient 2

Patient 3

Image Source: Wikimedia Commons.

Pairs of Sequences are Compared to Each Other

Papaya: ATGGTGCCGGrape: ATGCTGCCG

Papaya : ATGGTGCCGTomato: ATGCAGCCG

Grape : ATGCTGCCGWatermelon: ATGGACACG

Tomato : ATGCAGCCGWatermelon: ATGGACACG

Papaya: ATGGTGCCGWatermelon: ATGGACACG

Grape : ATGGTGCCGTomato: ATGGTGAAG

Number of Nucleotide Differences:

Papaya Grape Tomato WatermelonPapaya 0 1 2 3Grape 1 0 2 4Tomato 2 2 0 3Watermelon 3 4 3 0

Image Source: Wikimedia Commons.

Phylogenetic Trees Reflect Evolution

Internal Nodes(Common Ancestors)

External Nodes

Image Source: Wikimedia Commons.

Phylogenetic Trees: The CarnivoresRelatedness of Major Carnivores

Internal Nodes(Common Ancestors)

Domestic CatFelis catus

Gray WolfCanis lupus

RaccoonProcyon lotor

Spotted HyenaCrocuta crocuta

Cats

Civets

Mongooses

Hyenas

Canids

Bears

Red PandasSkunksWeaselsRaccoons

SealsFur SealsSea Lions

Walruses

Dog/Bear Branch

Cat Branch

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)

‘Spanish Flu’ H1N1 1918Pandemic H1N1 2009

California/7/2009California/4/2009Mexico/4/2009

New York/1/1918South Carolina/1/1918

Puerto Rico/8/1934Denver/1/1957

Brisbane/57/2007Solomon Islands/3/2006

New Caledonia/20/1999

‘Seasonal Flu’ H1N1 0.08% different

Scale:

Influenza Image Source: Wikimedia Commons.

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.

Phylogenetic Trees with an Outgroup Provide a Point of Reference

Laminaria (brown algae)

Outgroup:

Tomato

Grape

Papaya

Watermelon

Image Source: Wikimedia Commons.

MicrobiologistLalita 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