The Unifying Concept in Unifying Concept in BiologyBiology

Dr. Carol Eunmi LeeDr. Carol Eunmi Lee

University of Wisconsin, MadisonUniversity of Wisconsin, Madison

EVOLUTIOEVOLUTIONN

Theodosius Dobzhansky (1900-1975)

““Nothing in biology Nothing in biology

makes sense except in makes sense except in

the light of evolution”the light of evolution”

Who am I?

BA, MA from Stanford UniversityAnthropology (Human Evolution)

PhD, University of WashingtonEvolutionary Genetics

Postdoc, University of California, San DiegoEvolutionary Physiology and Biochemistry

Professor, University of Wisconsin, MadisonCenter of Rapid Evolution, Zoology, Genetics

TA

Marijan Posavi: Ph.D. Animal Science, Ph.D. candidate in Zoology

Will lead optional discussion (times posted on website)

He has office hours and can help with understanding the course material, but, he is NOT a private tutor (not possible for ~100+ students)

Please contact me if you are having trouble with this course and need a tutor

Research in my Lab

Adaptation, Functional evolutionary genomics, Physiological Evolution

Rapid evolution of invasive species entering the Great Lakes (zebra mussels, quagga mussels, copepods)

Evolution of microbial species carried by these invaders

Course Website

https://mywebspace.wisc.edu/carollee/web/Lee/Evolution410.html

***Background needed for this course

Some understanding of basic genetics (Hardy Weinberg Equilibrium, DNA, RNA, transcription, translation, allele, genotype)

Results from diagnostic quiz

N = 98 Mean = 5.59 ± 2.00

Evolution of a Pathogen as an Example:

I will now use an infectious disease to illustrate basic evolutionary concepts.

The following example illustrates several evolutionary mechanisms

I will explain these concepts in more detail over the next few lectures

HIV infects

macrophages,

T-cells

HIV: Fastest evolving organism on Earth

AIDS PandemicAIDS Pandemic

#people living with HIV

AIDS is among the most deadly epidemics in Human History (1981-2012: ~36 million deaths)

~34 million people living with AIDS (estimated 2010)

90 million deaths predicted by 2020

UNAIDS. 2008 Report on the Global AIDS Epidemic

(http://www.unaids.org/en/KnowledgeCentre/HIVData/GlobalReport/2008/)

A global view of HIV infection33 million people [30–36 million] living with HIV, 2007

ProblemProblem :: HIV has the fastest mutation rate of any virus or organism

observed to date

HIV evolves more rapidly than humans, and more quickly than the ability of humans to produce new drugs

Implications: AIDS vaccines are unlikely to work on all strains of the virus… …and unlikely to work on a given strain in the long run

Our understanding of how to combat viruses had in general been poor, and the recent intensive research on HIV has greatly enhanced our understanding of how to combat viruses in general

Evolutionary History of HIV

http://www.sciencemag.org/cgi/content/full/313/5786/462

Time

HIV evolved multiple times from SIV (Simian Immunodeficiency Virus)

There are multiple strains of HIV of different evolutionary origins and with different properties (coat proteins are divergent)

HIV Retrovirus with two single strand RNA genomes

Uses Reverse Transcriptase to replicate RNA --> DNA

Attacks host immune system: infects host macrophages and helper T cells

(Review in textbook on HIV)(Review in textbook on HIV)

HIV virion latches onto proteins on surface of host cell

Evolutionary Forces operating during HIV infection

Genetic Drift (Lecture 6): Viruses and bacteria in general have huge population sizes, where genetic drift tends to be less important

Mutation (Lecture 7): Fastest mutation rate known. Lots of genetic variation is produced. Virus can respond very quickly to Natural Selection

Natural Selection (Lecture 10): Selection is imposed by the host immune system Very strong selection is imposed by drugs

Transmission rate selects on levels of Virulence (tendency to cause disease). When transmission of virus to new hosts is rapid, selection favors strains that are more harmful to host

Evolution in a Host-Parasite SystemEvolution in a Host-Parasite System(Coevolution)(Coevolution)

I will now discuss how NATURAL SELECTION acts on HIV:

(1) Drugs impose Selection on HIV:--> evolution of drug resistance--> evolution of drug resistance

(2) Transmission Rate imposes Selection on HIV:Transmission Rate imposes Selection on HIV: --> evolution of virulence--> evolution of virulence

(3) Host immune system also imposes selection on the (3) Host immune system also imposes selection on the virus HIV virus HIV talk more about this in lecture on Selection talk more about this in lecture on Selection

(1) Selection in Response to Drugs

Several Types of Drugs:

Reverse transcriptase (RT) inhibitors, interrupts early stage of virus replication. Example: AZT

Protease inhibitors, interrupts virus replication at a later step in its life cycle

These drugs do not cure people of AIDS, they only retard the progress of the disease

Why does AZT work initially but fail in the long run?Why does AZT work initially but fail in the long run? AZT (Azidothymidine) is a thymidine mimic which stops

reverse transcription and impedes viral replication

Mutations in the viral reverse transcriptase gene of HIV arise, such that the enzyme can recognize AZT and cease to incorporate it

These mutations slow down viral genome replication (as the reverse transcriptase becomes more careful), but confer resistance to AZT (Tradeoff between speed vs. accuracy of reverse transcription)

These slow and careful mutants are favored by selection Viral resistance to AZT evolves within human hosts… (takes

about 6 months)

When AZT therapy stops, back mutations that restore the Amino Acid sequence to the original state are then favored by selection so that reverse transcription could speed up again (fast & sloppy are favored – because fast replicating mutants would outgrow the slower)

AZT

AZT (Azidothymidine) is a thymidine mimic which stops reverse transcription and impedes viral replication

• In the presence of AZT, Selection favors mutants that are resistant to AZT

• Resulting in a change in % in the population, toward a higher % of AZT resistant mutants

Why does AZT work short term but fail in Why does AZT work short term but fail in the long run?the long run?

The drug AZT imposes Selection on the virus. High levels of genetic variation (generated by high mutation rate) allows the virus to respond to selection and evolve drug resistance.

HIV has a high mutation rate because its reverse transcriptase is extremely error prone, causing mutations to often arise in the viral genome.

Occasionally a mutation can be favorable (as in the case of resistance to AZT), and would be favored by selection, leading to an increase in % of the new favorable mutant in the population of viruses

AZT

(2) Selection on Virulence of HIV Need to keep host alive long enough to get

passed on to the next host (Evolutionary tradeoff between fast population growth versus keeping the host alive)

High Transmission rate : High Virulence(Can grow fast and jump to the next host; ok if host dies; the genetic strain that grows faster will win)

Low Transmission Rate : Low Virulence(More virulent strains would die with the host and get selected out; less virulent strain that does not kill the host will win)

Selection on Virulence High Transmission: High Virulence

High Transmission Rate

If the virus is likely to move to a new host, the faster growing (and more virulent) strain is likely to overtake the slower strains and “win”

It’s ok to kill the host, since the chances of jumping to a new host is high

Natural selection will favor the MORE virulent strain

Selection on Virulence Low Transmission: Low Virulence

Low Transmission Rate

If the virus is not likely to move to a new host the slower growing (and less virulent) strain is likely to “win”

It’s not ok to kill the host, since the chances of jumping to a new host are low. If the virus kills the host, it will kill itself

Natural selection will favor the LESS virulent strain

EvolutionEvolution in Host-Parasite System in Host-Parasite System

SELECTION ON THE HOST (Humans)

Some humans have resistance to some HIV strains. Likely that the proportion of people with resistant alleles will increase.

Gene Therapy? Could we win an arms race?

But HIV evolves faster than we do

and more quickly than our ability to produce new drugs

The Geographic Spread of the CCR5 Δ32 HIV-Resistance Allele

Novembre et al 2005, PLOS Biology

Frequency of CCR5 Δ32 allele (Figure 1.20 in Freeman & Herron)

Combating HIVCombating HIV

(A) Because population growth rate of HIV is so high

(B) Because mutation rate of HIV is so high

(C) Because transmission rate of HIV is so Low

(D) Because selection acting on HIV is so high

Sample Exam Question:

1: Why is it difficult for scientists to develop drugs that could cure patients of HIV? Pick the most correct answer.

(A) Applying a greater diversity of antiviral drugs to the AIDS patient

(B) The widespread use of contraceptives (such as condoms) that would reduce the probability of transmission to the next host

(C) Increasing transmission rate of the virus such that a less virulent strain evolves

(D) Reducing rate of mutation rate by using drugs that slow down reverse transcriptase, such as AZT

Sample Exam Question:

2: Which of the following would most likely reduce the virulence (lethality) of HIV, the virus that causes AIDS?

Dr. Carol Eunmi LeeUniversity of Wisconsin, Madison

History History of of Evolutionary Evolutionary

ThoughtThought

(1) Development of Darwin’s Thought

(2) Lamarck vs. Darwin

(3) The Contribution of Darwin

(4) The Contribution of Mendel

(5) Conflict between “Mendelism” and “Darwinism”

Next time, the “Evolutionary Synthesis” of

Mendel and Darwin

Today’s OUTLINE:

Charles Darwin (1809-1882)

Origin of Species

is one of the most influential texts of this century

Charles Darwin (1809-1882) His father was a doctor (Richard Darwin) and his

grandfather was Erasmus Darwin, also a doctor and a prominent scholar who was already thinking about evolution

Initially he studied Medicine at the University of Edinburgh He neglected his studies and could not stand the sight of

surgery or the sight of blood (had nausea, fainted)

Sent by his father at Christ’s College, Cambridge University to become an Anglican priest

He still neglected his studies, but he did pursue a passionate interest in Natural History

He became close to botany professor Rev. John Henslow and met other leading naturalists who saw scientific work as religious natural theology (and viewed adaptation [i.e. evolution] as God acting through laws of nature)

“I fully believe a better man never walked this earth”

Charles Darwin to J.D. Hooker, 1861

Darwin’s Botany professor at Christ’s College (Divinity School), Cambridge University

Henslow encouraged students to make observations of their own, rather than being spoon-fed

After Darwin completed his final examination in 1831, Henslow persuaded him to begin studying geology, and made arrangements for him to take Adam Sedgwick’s geology course and a trip to map geological strata in North Wales

Shortly thereafter, in 1831, Henslow encouraged Darwin to join the Voyage of the Beagle as the ship’s naturalist

Reverend John Stevens Henslow (1796–1861)

More on Henslow:

Darwin's Mentor: John Stevens Henslow

1796–1861

By Walters & Stow

HMS Beagle off of South America

Voyage of the Beagle

HMS Beagle, a ship sent by British Navy to chart coastline of South America

During the 5-year Voyage Darwin was supposed to be primarily a

geologist; He had some expertise in geology, beetle collecting and dissecting marine invertebrates

He made observations on geological formations as the ship was mapping the coastline

At Punta Alta in Patagonia he made a major find of fossil bones of huge extinct mammals in cliffs beside modern seashells, indicating recent extinction with no signs of change in climate or catastrophe (“extinctions happen”)

The Galapagos Islands

Archipelago of volcanic islands distributed around the equator in the Pacific Ocean, 972 km (525 nmi) west of continental Ecuador

The Galapagos Islands

Why were these islands so important in shaping Darwin’s thinking?

The Galapagos Islands

• As an archipelago, there were many islands with different populations of a “species” on each island

• The populations were related, but were slightly different on each island… (not clear boundaries)

• This led Darwin to conclude that the populations descended from a common ancestor… and he ultimately concluded that they had evolved and were evolving…

• led Darwin to question the stability of the concept of a “species”

Darwin’s Mockingbirds

"My attention was first thoroughly aroused by comparing together the various specimens ... of the mocking-thrush"

C. Darwin, The Voyage of the Beagle (1839)

• On Sept 17 1835, Darwin disembarked from the Beagle in the Galápagos near Sappho Cove on Chatham Island (now known as Isla San Cristóbal), and was struck by the bold, terrestrial mockingbird.

• The bird is known today as Mimus melanotis, the San Cristóbal Mockingbird. Over the next 6 weeks that Darwin spent in the Galápagos, he observed mockingbirds on three other islands.

• Darwin noticed the mockingbirds differed between islands. Nicolas Lawson, acting Governor of Galápagos, told Darwin that the tortoises also differed from island to island.

• Towards the end of the voyage, Darwin speculated that the distribution of the mockingbirds and the tortoises might "undermine the stability of Species”. Species might not be fixed entities, but are changing over time…

Galapagos Islands

Darwin’s Mockingbirds (he did not focus that much on the finches; they were studied more later by the Grants)

Tortoises and other animals

Mockingbirds on different islands differed slightly in size, shape and coloration

And all shared some traits (homologous traits)

He concluded that these birds must have shared a common ancestor--and were not independently created

Significance of the HMS Beagle Voyage

• Collections to study later

• Exposed Darwin to geological formations, fossils embedded in strata – animals that no longer exist today and are clearly extinct – this was known, but Darwin got to see this himself

• Exposure to animal diversity, related populations within species living in different habitats:

1. “Species” are not immutable fixed entities2. Organisms are related by common ancestry (tree-like

branching)3. They are changing and branching in response to the

environment

Return to England Returned and discussed his

geological and biological finding with other scholars, influenced by Malthus, etc.

Married the wealthy Emma Wedgewood

Did not have to work, and could study the samples he collected, perform experiments, make observations, think, and write books for the rest of his life

Historical Context:Historical Context:

By mid-1800s scientific context was in place for development of theory of Evolution

Developments in Geology: Discovery that earth is more than 6,000 years old

Fossil Record showed change in species over time

http://www.ucmp.berkeley.edu/history/evotmline.html

Influences on Darwin

Geology: Darwin had Lyell’s Principles of Geology on board the HMS Beagle

Lamarck ’s (1744-1829): Concept of Adaptation, Inheritance of acquired characteristics

Malthus (1766-1834): Competition within species and struggle for survival

Geology: Darwin had Lyell’s Principles of Geology on board the HMS Beagle, given to him by captain of the HMS Beagle (Robert FitzRoy)

Fossil record: The earth is old Many animals that once existed are now extinct There are layers (strata) in the fossil record show

a pattern of change

Influences on Darwin

Jean-Baptiste Lamarck

French Naturalist (1744-1829)

“Professor of Worms and Insects” in Paris

The first scientific theory of evolution (inheritance of acquired characteristics)

Influences on Darwin

Lamarck ’s (1744-1829) theory of Evolution

Inheritance of acquired characteristics

Proposed the most influential mechanism of evolution before Darwin:

Introduced the idea of Adaptation, though he was mostly incorrect on the predominant mechanism (though sometimes correct; will discuss Epigenetic Inheritance)

The idea of competition: Malthus’ calculations showed that rate of population

growth was greater than rate of increase in food supply

Thus, not all individuals could possibly survive

Based on this fact of competition, Darwin concluded that individuals that are better adapted would be the ones that survive and leave more offspring (and win the competition)

Influences on Darwin

food

Population

Thomas Malthus (1766-1834): “Essay on the Principle of Population”

Malthus

From Malthus, Darwin came up with the idea of competition and the “struggle for survival” as a component of Natural Selection

The scientific community was primed for a theory of Evolution

Darwin was one of many scholars at his time that were thinking about Evolution

Many scholars accepted the idea of Evolution at the time… what puzzled them was the mechanism

In fact, Alfred Wallace (1823-1913) came up with the idea of natural selection independently

Darwin rushed to publish Origins in 1859 when he learned of Wallace’s work

Based on his work in the Malay Archipelago

He also studied populations on different islands and came to the same conclusion as Darwin

Alfred Russel Wallace (1823-1913)

“On the Tendency of Varieties to Depart Indefinitely from the Original Type”

In 1858 Wallace sent Darwin a copy of his manuscript

Darwin was shocked that Wallace came up with the idea of natural selection independently

They decided on a joint presentation at the Linnean Society in 1858, but it received little attention

After which Darwin rushed to publish his book in 1859

Alfred Russel Wallace (1823-1913)Father of Biogeography… focused on adaptation to the environment

Charles Darwin (1809 -1882)

On the Origin of Species (1859)

Living species are related by common ancestry

Change through time occurs at the population not the organism level

The main cause of adaptive evolution is natural selection

Darwin’s Main Points

(1) Organisms Evolve (Darwin not first)

(2) Common Descent: species arise from common ancestors (tree thinking) (Wallace also)

(3) Gradualism: changes are gradual (still debated)

(4) Population Speciation: change in proportions of individuals having a trait in a population (Wallace also)

(5) Natural Selection: mechanism (Wallace also)

Before Darwin had developed his ideas on the mechanism of evolution, Lamarck had proposed an alternate mechanism that was popular at the time

Lamarck vs Darwin

(1) Different View on pattern of Evolution Lamarck: Linear progression Darwin: Tree-like branching process

(2) Different View on Mechanism of Evolution Lamarck: inheritance of acquired traits (not mutations)--

Individual evolution Darwin: Evolution at the Population Level via Natural

Selection

Lamarck vs Darwin

Lamarck’s View on Pattern of Evolution Continuum between physical and

biological world (followed Aristotle)

Scala Naturae (“Ladder of Life” or “Great Chain of Being”)

“Transmutation of Species” –one species turns into another

Linear progression from primitive to advanced

Being

Realm of Being

Realm of Becoming

Non-Being

God

Angels

Demons

Man

Animals

Plants

Minerals

What is wrong with a ladder?

Evolution is not linear but branching

Living organisms are not ancestors of one another

The ladder implies progress

Darwin envisaged Evolution as a Tree

The affinities of all the beings of the same class have sometimes been represented by a great tree. I believe this simile largely speaks the truth………The green and budding twigs may represent existing species; and those produced during former years may represent the long succession of extinct species…..….the great Tree of Life….covers the earth with ever-branching and beautiful ramifications

Charles Darwin, On the Origin of Species; pages 131-132

The only figure in Origin of Species

Charles Darwin's 1837 sketch, his first diagram of an evolutionary tree from his First Notebook on Transmutation of Species (1837) on view at the the Museum of Natural History in Manhattan.

Interpretation of handwriting: "I think case must be that one generation should have as many living as now. To do this and to have as many species in same genus (as is) requires extinction . Thus between A + B the immense gap of relation. C + B the finest gradation. B+D rather greater distinction. Thus genera would be formed. Bearing relation" (next page begins) "to ancient types with several extinct forms"

Lamarck’s View on Mechanism of Evolution

Individuals are evolving If you got a tan, you’d pass it on

Individuals are evolving If you got a tan, you’d pass it on

Some balls get tan during their lifetime

Lamarck’s View on Mechanism of Evolution

Individuals are evolving If you got a tan, you’d pass it on

Tan balls pass on their acquired trait to their offspring

Lamarck’s View on Mechanism of Evolution

(We now know that acquired traits could get passed on sometimes when epigenetic modifications are inherited)

Natural Selection

Darwin’s View on Mechanism of Evolution

A heritable difference(now known to be due to different mutations)

Natural Selection

Darwin’s View on Mechanism of Evolution

Selection mightfavor this mutation

Natural Selection

Darwin’s View on Mechanism of Evolution

Greater Fitness: individuals with this mutation survive and leave more offspring

Natural Selection

Darwin’s View on Mechanism of Evolution

The individuals themselves are not changing, but the population is changing in composition (% of alleles)

Darwin’s contribution:

“Population Speciation as a result of Natural Selection”

More offspring are produced than can survive

Limited resources and competition for resources (“The Struggle for Survival”)

There is variation in a population

Individuals better adapted to environment survive

Survivors leave more offspring (“Survival of the

Fittest”)

Thus, average character of population is altered

So… Darwin did NOT originate

the idea of Evolution…

… BUT he provided a plausible Mechanism (along with Wallace)

… and much evidence

Chapters of Origins (1859) On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life1 Variation Under Domestication

2 Variation Under Nature

3 Struggle for Existence

4 Natural Selection

5 Laws of Variation

6 Difficulties on Theory

7 Instinct

8 Hybridism

9 On the Imperfection of the Geological Record

10 On the Geological Succession of Organic Beings

11 Geographical Distribution

12 Geographical Distribution continued

13 Mutual Affinities of Organic Beings: Morphology: Embryology: Rudimentary Organs

14 Recapitulation and Conclusion

Other books by Darwin on Evolution

The Variation of Plants and Animals under Domestication

The Descent of Man

The Expression of the Emotions of Man and Animals

Full list of books by Darwin: http://en.wikipedia.org/wiki/Charles_Darwin_bibliography

But… Darwin’s theory was not complete

Because Darwin knew nothing about mutation, he had no idea how variation was generated in populations (Lecture 7)

Because Darwin knew nothing about genetics or genes, he had no idea how variation was passed on to offspring (Mendel & Hardy-Weinberg)

Darwin did not know about nonadaptive evolutionary forces, such as Genetic Drift (Lecture 6)

Sample Exam Question

Which of the following was NOT part of Darwin’s theory of Evolution?

(1) Natural Selection

(2) Populations as the units of Evolution

(3) Mutations as sources of genetic variation

(4) Survival of those who produce more offspring

Mendel published in 1865… was ignored until 1900

Presented a mechanism for how traits got passed on

“Individuals pass alleles on to their offspring intact”

(the idea of particulate (genes) inheritance)

Mendel’s work held part of the key to what was missing in Darwin’s Theory

Hardy-Weinburg

Equilibrium (Lecture 3)

Wilhem Weinberg January 13, 1908

G. H. Hardy July 10, 1908 in Science

The Mathematical expression of Mendel’s Principles of Inheritance

Hardy-Weinburg

Equilibrium (Lecture 3)

Wilhem Weinberg January 13, 1908

G. H. Hardy July 10, 1908 in Science

Could mathematically show expectations of Mendelian inheritance and whether expectations are realized in nature

PROBLEMS!

BUT… Mendel and Darwin’s ideas seemed Incompatible

Mendel’s principles: dealt with particulate (discrete) traits (e.g. yellow vs. green, wrinkled vs. smooth)

BUT, Darwin observed continuous traits (e.g. beak size, body length)

Q: So, how would continuous traits get passed on?

Selection vs Mutations

Mutations discovered after 1900

Q: If mutations are arising, why need selection... … if things are just mutating?

Controversy between Mutationists vs Darwinists

Mutationists (+Mendelianism) They thought that evolution required only

mutations and passing on of discrete traits

Darwinists They thought that evolution required only

Natural Selection on continuous variation

Controversy between Mutationists vs Darwinists

Controversy persisted for ~30 years up till the 1930s, during which little progress was made

Problem caused by: Binary thinking (Black or White thinking): it’s this

or that… “if I’m right, you must be wrong”

When in fact the two or more factors might interact

Inability to see overarching mechanism that could explain a wide range of phenomena: “How could your Hardy-Weinberg (Mendel) explain the inheritance of 5.1 cm, 5.5 cm beak length (continuous characters)?”

When in fact, another factor might make it possible (think multiple genes, rather than one gene)

Genetic Drift (Lecture 5)

A concept as important as Natural Selection But, not as prominent on people’s minds

1872 Gulick: Neutral Theory (Genetic Drift) 1921 A.C. Hagedoorn produced data to support

Neutral Theory of Genetic Drift

The Modern SynthesisThe Modern Synthesis1930s ~ 1940s

The synthesis of population genetics

(role of mutation, genetic drift),

paleontology, systematics

Darwin and Mendel Reconciled!!!(Next Lecture)

Questions:Questions:(1) What were the intellectual influences on Darwin’s thought?

(2) What role did the discoveries from the Beagle’s voyage play

in the development of Darwin’s thought?

(3) What were Darwin’s main conclusions?

(4) How did Darwin’s thought differ from that of Lamarck?

(4) What did Darwin’s theory leave out?

(5) What was Mendel’s contribution?

(6) What were the sources of confusion between the proponents

of Darwin and Mendel’s ideas?

CONCEPTSCONCEPTS

Evolution

Population

Natural Selection

Evolutionary Adaptation

Fitness

Mutation

Genetic Drift

Recombination

Hardy-Weinberg Equilibrium

Development of Darwin’s thought

Lamarck vs Darwin

Darwinists vs Mendelists

Evolutionary Synthesis

1.Which of the following is TRUE regarding Darwin’s contribution to the theory of Evolution?

(A) Darwin formulated the first comprehensive theory incorporating all mechanisms of evolution

(B) Darwin recognized that evolution occurs at the population level (in terms of changes in frequency of traits within populations)

(C) Darwin proposed that selection acts on mutations and other forms of genetic variation

(D) Darwin agreed with Larmarck’s idea of inheritance of acquired characters, but included the concept of fitness.

(E) Darwin incorporated Mendel’s work on the particulate inheritance of alleles

Sample Exam Questions

2. For several decades "Darwinists" and "Mendelists" battled over the mechanisms of evolution. Which of the following did NOT contribute to this particular conflict?

(a) Geneticists/Evolutionary biologists did not understand that continuous and discrete traits follow the same principle of inheritance

(b) Geneticists/Evolutionary biologists did not understand that natural selection acts on mutations in a population

(c) Mendel worked with discrete traits, whereas Darwin worked with continuous traits, leading to differences in perspectives on inheritance

(d) Darwin was unaware of the mechanism or unit of inheritance

(e) Darwin was unaware of the mechanisms of Genetic Drift

3. Darwin’s development of the theory of evolution by natural selection was NOT influenced by which of the following?

(a) The concept of adaptation to the environment, which was proposed by Lamarck

(b) Fossils of extinct organisms

(c) Each island of an archipelago having a population with morphological differences from those on other islands

(d) Malthus' demography showing exponential growth of populations

(e) Changes in frequency of discrete characters from generation to generation