the history and science of molecular genetics timothy g. standish, ph. d

The History and The History and Science of Science of

Molecular GeneticsMolecular GeneticsTimothy G. Standish, Ph. D.

Chromosomes:Chromosomes:The Physical Basis of InheritanceThe Physical Basis of Inheritance

1866 Mendel published his work 1875 Mitosis was first described 1890s Meiosis was described 1900 Mendel's work was rediscovered 1902 Walter Sutton, Theodore Boveri and others noted

parallels between behavior of chromosomes and alleles. 1910 Thomas Hunt Morgan associates a trait with a

chromosome (white eyes on the Drosophila Y chromosome)

Molecular Genetics:Molecular Genetics:A Short HistoryA Short History

1869 - Miescher isolated DNA for the first time 1944 - Avery provided evidence that DNA is the genetic material 1953 - Watson and Crick proposed the double helix as the

structure of DNA 1957 - Kornberg discovered DNA polymerase 1961 - Marmer and Doty discovered DNA renaturation 1962 - Arber, Nathans and Smith discovered restriction

endonucleases 1966 - Nirenberg, Ochoa, and Khorana figured out the genetic

code.

A Short History Cont.A Short History Cont. 1967 - Geller discovered DNA ligase 1972-73 - Boyer, Cohen and Berg develop DNA cloning

techniques 1975 - Southern developed gel-transfer hybridization 1975-77 - Sanger and Barrel and Maxam and Gilbert developed

rapid DNA sequencing methods 1981-82 - Palmiter and Brinster produced transgenic mice,

Spradling and Rubin produced transgenic fruit flies 1985 - Mullis and colleagues invented the Polymerase Chain

Reaction (PCR)

What is Science?What is Science? “Sci” = Knowledge “ence” = The condition of Explanation of natural phenomena through

observation and experimentation A method of gaining knowledge (the scientific

method)

The Scientific MethodThe Scientific Method

The Scientific method relies on two types of reasoning: Inductive reasoning - The drawing of generalized

conclusions from a collection of data, this is the type of reasoning used when coming up with a theory

Deductive reasoning - Elimination of possibilities until only one or a very few remain. Hypotheses are testable statements that must be true if a theory is true, thus if the hypothesis is not true, the theory can be deducted from the set of possible theories.

DataHypothesis

Theory

Pass

Beliefs

Indu

ction

Fail

The Scientific MethodThe Scientific Method

Deduction

Test(Experiment)

DataErr

orThe Scientific MethodThe Scientific Method

Does Not Always Provide Does Not Always Provide Definitive AnswersDefinitive Answers

Time

OldTheory

PresentScience

Truth

Understanding ScienceUnderstanding Science Scientists must understand the difference between facts (data)

and interpretation (theory) Fact - Chimpanzees and humans have DNA that is 98 - 99 %

identical Interpretation 1 - Chimpanzees and humans share a common

ancestor Interpretation 2 - Chimpanzees and humans share a common

Designer Most data is open to multiple interpretations Theory ≠ Fact

ReductionismReductionism Organisms are too complex to study as a whole, so biologists

break them down to their components assuming that knowing each part’s workings gives insight on the whole organism.

Understanding the digestive system requires study of the digestive organs. Understanding the esophagus, stomach and intestines helps us understand the system.

Cells, the fundamental units of life, can be understood in light of biochemicals (proteins, lipids, carbohydrates etc.) from which they are made.

Selection works at the level of macro molecules, not on their chemical components

Emergent PropertiesEmergent Properties Biological systems are more than just the sum of their parts,

the combination of parts produce “emergent” properties only present because of the combination and not intrinsic to any single part.

A wheel is not a transportation device and neither is a bicycle frame, put them together with a few other parts and they become a bicycle.

The heart would not pump blood if it was only the ventricles contracting, or just valves ensuring blood flows in only one direction. Combination of ventricles and valves moves blood through the heart and out to the body.

Biologist’s DilemmaBiologist’s Dilemma Life is too complex to study as a whole, thus reductionism

must be used to simplify biological systems to the point they can be understood

The “simple” components that make up living things have emergent properties present only when they are combined together.

In other words, the whole is greater than the sum of the parts Understanding how the components work does not

necessarily tell us how the organism works.

The Limit of Reductionism?The Limit of Reductionism? Because biologists can’t know what other parts interact

with the part they are studying without knowing some emergent properties of those parts together, it seems that in many (all?) cases understanding emergent properties on the basis of a part’s properties is not possible

This is not to say that emergent properties cannot be inferred from comparison of one part with another related part for which the function is already known

Board

Behe’s InsightBehe’s Insight Michael Behe contends that when we look at the

protein machines that run cells, there is a point at which no parts can be removed and still have a functioning machine. He called these machines “irreducibly complex” (IC)

We encounter irreducibly complex devices in everyday life. A simple mouse trap is an example of an irreducibly complex device:

HammerSpring

Trigger

Bait holder

CheeseStaple

CAPCAP

5’AANTGTGANNTNNNTCANATTNN3’

3’TTNACACTNNANNNAGTNAAANN5’

GeneticsGenetics In one sense, genetics could be considered to be

the ultimate exercise in reductionism on the part of biologists.

Genes serve as the blue print for life. All proteins are defined by genes, and all other macromolecules are made by proteins.

All emergent properties are ultimately defined by genes

GeneticsGenetics In one sense, genetics could be considered to be

the ultimate exercise in reductionism on the part of biologists.

Genes serve as the blue print for life. All proteins are defined by genes, and all other macromolecules are made by proteins.

All emergent properties are ultimately defined by genes

Molecular GeneticsMolecular GeneticsMolecular genetics studies biology at

the fundamental point where chemicals meet to produce the emergent property we call life

Does understanding molecular genetics mean that we understand life?