Cell Biology

I. Overview

II. Membranes: How Matter Get in and Out of Cells

III. Harvesting Energy: Respiration and Photosynthesis

IV. Using Energy I: Protein Synthesis

V. Using Energy II: Cell Reproduction

Cell Biology redux - why is this cell unit important, again?

This cell biology unit is getting pretty long! We have discussed lots of very complicated processes at a molecular and cellular level. It would be very easy to "lose sight of the forest for the trees" - to become lost in the details of these processes and to lose sight of their relevance to the evolutionary theme of the course.

This cell unit is supposed to provide you with a firm foundation regarding what DNA IS and what it DOES. Only then can you truly appreciate why differences in DNA cause some of the variation we see between cells, tissues, and multicellular organisms. We have seen that proteins are instrumental in nearly everything that cells - and therefore tissues, organs, and living organisms - do. Specific proteins regulate the flow of material into and out of the cell (protein channels). Specific protein catalysts (enzymes) co-ordinate the chemical reactions in the cell; reactions that break down food (respiration) and harvest light energy (photosynthesis), and reactions that build all the organic molecules needed in a particular cell (like proteins in protein synthesis). Proteins are important structural components of cells and organisms, too; like the actin and myosin in contractile muscle cells, and the collagen in skin and bone tissue. The functions these proteins play is determined, in part, by their primary structure - their sequence of amino acids. Because the sequence of nitrogenous bases in DNA is the primary determinant of the sequence of amino acids in a protein (as we saw in protein synthesis), it is the DNA sequence that is ultimately responsible for what proteins do and what cells do. So, this cell unit was supposed to provide you with an appreciation for how a cell functions and how the genetic system controls this activity through the production of proteins.

So, THIS IS WHY our understanding of DNA structure, function, and heredity are so important to evolutionary theory. Changes in this heritable information cause changes in the physiological, morphological, and behavioral characteristics of organisms. HOW do changes in the DNA cause these changes in the physiology, morphology, and behavior of organisms? Hopefully, the previous paragraph answered that question for you - by changing the proteins that are responsible for cell, organ, tissue, and organism structure, function, and development. You can only really understand this if you understand what proteins do in a cell. And that is why cell biology is important to our understanding of evolution; it is where DNA does its work, and it is where evolutionary, genetic change has its most immediate biological effect.

Overview:

1. Why reproduce?

Living systems reproduce. In many ways, reproduction seems like the most purposeful thing that living systems do. Indeed, most nature shows describe this attribute as a "desire", "goal" or "urge", often described in these same shows as a process performed "in order to perpetuate the species". Well, it is currently impossible for us to ascertain the "desires", "goals" or "urges" of an ameoba or an oak tree; or whether the amoeba or oak tree is 'thinking' about the survival of its species as it reproduces. Thankfully, Darwin's theory of natural selection absolves us from having to understand "desires" - it explains the existence of complex physiology, morphology, and behavior as a function of the relative benefit of that trait to relative reproductive success.

In this context, the adaptive value of reproduction is as obvious as the the difference between "1" and "0". Think about it this way: the natural world is a dangerous place. It is exciting and fun for a while, but all living things will eventually die as a consequence of encountering an environment in which they cannot survive (flood, fire, heat, or cold), or being eaten by a predator, or infected by a pathogen, or simply by accident. So, the only life forms that will persist through time are those that copy themselves at a faster rate than they are dieing. This works from the cell level through the populational level, and even at the phylogenetic level with respect to the persistence of particular lineages through geologic time. So, for any population, if the birth rate remains lower than the death rate then population will eventually go extinct. In a multicellular organism, if the rate of cell production is lower that the rate of cell death, the organism will waste away, losing tissue mass. At a geologic scale, lineages that produce species faster than the extinction rate will persist longer through time that lineages where the rate of speciation is lower than the rate of extinction. So today, when we look at the entire diversity of the living world, we only see descendants of those life forms that reproduced. And these living life forms have inherited this capacity to reproduce, as well.

In terms of natural selection, members of a population that do not reproduce at all have a differential reproductive success of "0". Selection will favor organisms that evolve the capacity to reproduce. For prokaryotes, cell reproduction occurs by binary fission. For eukaryotic cells, cell reproduction occurs by mitosis. In single-celled protists, mitosis produces two new organisms. In multicellular organisms, mitosis produces new cells that can replace dead cells or increase the number of cells in the organism. If the net number of cells increases, the multicellular organism grows. As we have mentioned before, growth is usually a good thing. First, the bigger you are, the fewer things can eat you. Second, becoming larger through multicellularity allows for the increased efficiency and functional diversity of cell specialization.

2. An overview of cell division:

Cell division is the process of producing two functional 'daughter' cells from one ancestral 'parental' cell. In order for both of the daughter cells to have the full functional repertoire of the original parental cell, they must be able to make the full complement of proteins that the parent cell makes. In order for this to happen, they must both receive the full complement of genetic information (DNA) in the parental cell. Hmmm.... how can they BOTH get the FULL COMPLEMENT of genetic information in the parental cell? Well, in order for this to happen, the parental cell must duplicate its DNA prior to cell division. This process of DNA replication produces two full complements of genetic information. Then, this genetic information must be divided evenly, in an organized manner, to insure that both daughter cells get the complete complement of information (and not a duplication of some information or an omission of other information). Cells that receive an incomplete complement of genetic information will not be able to make all the proteins the parental cell made, and may not be able to survive. So, again, DNA replication and the process of mitosis are of great selective, adaptive value. Only cells that replicate and divide their genetic information evenly, with only minor errors or inconsistencies, will be likely to survive. These survivors will pass on the tendancy to replicate and divide their genetic information evenly, as well. So, there is very strong selection ( a very large selective advantage) for correct DNA replication and equal chromosomal allocation during mitosis.

These processes of DNA replication and mitosis are only two stages in the life of a cell. To place them in context, it's useful to consider the full life of a cell, from it's production by the division of its parental cell through to its own division.

A. The Cell Cycle

1. Interphase - the 'interval' between divisions

a. G1

Our cell's life begins. That's sort of a funny way to put it, because it seems to suggest that it is something new; yet all of its constituents were part of the original parental cell. It is more truly "1/2 an old cell with a full complement of DNA". Nevertheless, it is an independent entity. In most protists, binary fission of the mitochondria and chloroplasts occurs concurrently with the division of the nucleus during mitosis, so the daughter cells have 'new' organelles, too. But in most multicellular organisms, the allocation of organelles is largely a random process based on how they are distributed in the cytoplasm during division. Then, the organelles divide and 'repopulate' each daughter cell in G1.

The cell is roughly 1/2 the size of the original parental cell. To grow to its appropriate size, it must synthesize new biological molecules - and that means making the enzymes that will catalyze those reactions. So, the DNA unwinds to the 'beads on a string' level, and the genes between histones are available for transcription. When the DNA is unwound ('diffuse'), separate chromosomes cannot be seen with a light microscope. Rather, the nucleus stains a uniform color except for one or several dark regions called 'nucleoli' (singular = nucleolus). These are areas were large amounts of r-RNA are being synthesized and complexed with ribosomal proteins into functional ribosomes. The ribosomes are exported from the nucleus to the cytoplasm, where they will anchor to endoplasmic reticulum or the cytoskeleton.

Indeed, the G1 phase of a cell's life is the most metabolically active period of it's life. It is growing in size, and producing the proteins appropriate for its tissue type. Most cells in multicellular organisms specialize during this period. Cells with very specific structural adaptations to their specialized tissue type - like neurons with long axons and muscle cells crammed with linear microfilaments - often remain stalled in this stage after they become specialized; they do not divide again. In this case, this stalled 'permanent' G1 phase is referred to a G0 ("G-nought').

b. S

The S phase of the cell cycle is when DNA replication occurs. The chromosomes are diffuse during this stage, as well, so the enzymes (DNA polymerases) that replicate the DNA can access the helices. Each double helix is separated, and the single strands are used as templates for the formation of new helices on each template - changing one double helix into two. Terminology becomes a bit ambiguous here. A DNA double helix is equivalent to a "chromatid". A chromosome may have one chromatid (in its unreplicated form) or two chromatids (in its replicated form). DNA replication is a rather complicated process described in more detail below. The transition from the G1 to the S phase is a very critical stage in a cell's life cycle, signalling the cell's progression towards division. In eukaryotes it is called a 'restriction point'. Once the S phase begins, the cell will proceed through to mitosis. This transition is orchestrated by a complex interplay of transcription factors that regulate the activity of "cell division cycle genes". These genes produce cyclin proteins that vary in concentration through the cell cycle. They bind with 'cyclin-dependent kinases' and these cdk-cyclin complexes activate transcription factors that initiate the next phase of the cell cycle.

The timing of the G1/S transition is very important. During the G1 phase, the DNA is 'checked' by repair enzymes... mismatched bases and other mutations are corrected. It is important that the G1 lasts long enough for DNA repair to take place; otherwise any errors will be copied during DNA replication and mutations will be passed to the next generation of cells. There are several proteins that inhibit the progression of the cell cycle - the most notable is called p53. This protein is a cell cycle inhibitor, indirectly causing the inactivation of cdk-cyclin complexes that would stimulate the onset of the S phase. Mutations in this gene can make the protein non-functional; so cdk-cyclins are not inhibited, and the onset of S happens quickly and prematurely - before DNA repair is completed. This mutation is passed to the daughter cells, too, along with all the other uncorrected mutations. These mutations accumulate with each generation of cell division, affecting other genes that influence cell function and specialization. This unregulated division of undifferentiated cells creates a cancerous tumour. There are several other 'tumor suppressor' genes, but mutations in p53 occur in 70% of small cell lung cancers, 80% of non-melanoma skin cancers, and 60% of colon cancers. Obviously, correct regulation of the cell cycle is critical to correct cell function and maintaining the integrity of DNA.

c. G2

After DNA replication is complete the cell goes through another rapid period of growth in preparation for mitosis. The DNA is checked again for damage caused and errors made during DNA replication. Once again, p53 inhibits the transition to the mitotic phase, providing time for this repair to take place. In cancer cells with mutations in p53, the G2 phase may be nearly eliminated, with the cell proceeding directly from DNA replication to mitosis. CDK's bind to new cyclins, and these complexes active a different set of proteins that initiate mitosis.

2. Mitosis

The process of mitosis can be summarized as follows: the chromosomes condense, making it easier to divy them up evenly. The replicated chromsomes are aligned in the middle of the cell by cytoskeletal fibers. Each chromosome consistes of two identical double helices, called chromatids. During the process of mitosis, these chromatids separate from each other, and one double-helix from each chromosome is pulled to each end of the cell. The membrane and cytoplasm are divided and the nuclear membrane reforms around the chromosomes in each daughter cell. We will look at this process in more detail, below.

B. DNA Replication

102 ALERT!! The presentation that follows is a bit too detailed... I want you to know:

1. Initiation

An assemblage of enzymes, collectively called a 'replisome', bind to the DNA molecule at sequences called 'replication origins'. Eukaryotes have large genomes, and there are hundreds or thousands of replication origins across the chromosomes in a eukaryotic genome.

Within the replisome, the enzyme helicase separates the helices, unzipping the DNA.

DNA replication begins in an unusual way. RNA polymerases, called RNA primases, create a short strand of RNA on each of the DNA templates, in a 5'-->3' direction. This occurs because DNA polymerases cannot initiate the process - they can only add bases to the 3' end of an existing nucleic acid. However, this may also be a "vestigial" structure of the ancestral RNA world - when RNA polymerases predated DNA polymerases and may have been used to produce the RNA genomes from the newly formed DNA template (formed from reverse transcriptase). The short piece of RNA is know as RNA primer; it provides a free 3'-OH group for the DNA polymerase to add DNA nucleotides. DNA Polymerases displace the primases and add DNA to both strands in a 5'--> 3' direction.

2. Replication "at the fork"

Of course, the anti-parallel nature of the DNA double helix creates a problem. As DNA is unwound (creating a 'fork' of single stranded DNA template) one template (the 'leading strand') is oriented 3'-->5' into the fork. No problem. As this DNA is unwound, DNA polymerase can extend the newly synthesized DNA in a complementary 5'-->3' direction. However, there is a problem on the other 'lagging' strand. The single stranded DNA template is revealed in a 5'-->3' direction on this strand, so polymerization of the new strand cannot be continuous into the fork (because synthesis of the new strand must be in a 5'-->3' direction, away from the fork). To replicate this strand, primase must create another short stretch of RNA primer, and DNA polymerase must elongate the strand 5'-->3' away from the fork.

Again, as the helicase continues to unwind the DNA, the leading strand can be replicated continuously, just by adding new bases that are complementary to the template. On the lagging strand, RNA primase must lay down another primer, and DNA polymerase must 'backfill' the gap, filling in the space "behind" the last RNA primer sequence. This is accomplished by the DNA forming a loop on the lagging strand, so it can be pulled through the replisome in the same direction as the leading strand. DNA polymerase fills in this space with DNA, but it does not link the DNA to the 5' end of the neighboring RNA primer. So, on this strand at this fork, DNA synthesis is discontinuous. Short fragments of DNA are created, beginning with a short primer of RNA. These fragments are called Okazaki fragments, after the scientist who identified them.

Because of the antiparallel nature of the double helix, the laggin strand at one fork is the leading strand at the other fork (see ppt. Also, on the picture to the right, think about how the botttom helix will be replicated to the left. The complementary strand can't be extended from the 5' end of the RNA primer. Instead, RNA primase must create anothe strand far to the left, and DNA synthesis must prceed left to right, 5'-->3', on this bottom strand. As more DNA is unwound to the left, this process must be repeated; creating Okazaki fragments on the bottom strand). So, there are fragments on both strands.

These videos provide good representations of this process, in a realistic (video 1), and more schematic (video 2) view. The discontinuous nature of replication on the laggin strand is easiest to understand in the ppt, and you will need to be able to draw this process in this way. The only thing that is not included is the looping, 3-d conformation that the lagging strand takes.

video 1

video 2

3. DNA Repair

Repair enzymes interact with the DNA, reacting with DNA that is too wide or narrow because of mismatched base pairs. In addition, repair enzymes cut out the RNA primers. Other DNA polymerases fill the gaps with DNA. Ligase forms the last phosphodiester bond, linking the fragments together.Eventually, the process of synthesis emanating from neighboring origins connect - and the entire chromosome is replicated.

This process separates two original helices, and builds new DNA on each old template. So, each new double helix contains one old helix from the original strand, and one newly synthesized strand. As such, this process is called "semi-conservative", because each new double helix conserves half of the original double helix. These two double helices, which are identical to one another, are connected at the centromere. Proteins aggregate at these sequences during mitosis, forming a structure called the kinetochore. The kinetochore anchors the chromosome to the fibers in the spindle apparatus during mitosis.

C. Mitosis

Mitosis is a continuous process of chromosome condensation, chromatid separation, and cytoplasmic division. This process is punctuated by particular events that are used to demarcate specific stages. This process was first described by Walther Flemming in 1878, we he developed new dyes and saw 'colored bodies' (chromo-somes) condensing and changing position in dividing cells. He also coined the term 'mitosis' - the greek word for thread - in honor of these thread-like structures.

1. Prophase: The transition from G2 to Prophase of Mitosis is marked by the condensation of chromosomes.

2. Prometaphase: The chromosomes continue to condense, and the nuclear membrane disassembles. The microfibers of the spindle apparatus attach to the kinetochores on the replicated chromsomes.

3. Metaphase: The spindle aranges the chromosomes in the middle of the cell.

4. Anaphase: The proteins gluing sister chromatids together are metabolized, and the sister chromatids are pulled by their spindle fibers to opposite poles of the cell. It is important to appreciate that these separated chromatids (now individual, unreplicated chromosomes) are idnetical to one another and identical to the orignial parental chromosome (aside from unrepaired mutations).

5. Telophase: The cell continues to elongate, with a concentrated set of chromosomes at each end. Nuclear membranes reform around each set of chromosomes, and the chromosomes begin to decondense.

6. Cytokinesis: Cytokinesis is sometimes considered a part of telophase. In this stage, the cytoplasm divides. In animal cells, the membrane constricts along the cell's equator, causing a depression or cleavage around the mid-line of the cell. This cleavage deepens until the cells are pinched apart. In plants, vesicles from the golgi coalesce in the middle of the cell, expanding to form a partition that divides the cell and acts as a template for the deposition of lignin and cellulose that will form the new cell wall between the cells.

As a consequence of this process, two cells are produced from one parental cell, each having a complete complement of genetic information - a copy of each original chromosome that was present in the parental cell. Each of these cells now begins the G1 phase of interphase.

A Darwinian View of Life

I. Overview: The Evolution of Biology

Overview

The idea of observing a natural phenomenon, proposing a testable hypothesis of causality to explain that phenomenon, and then testing that hypothesis to determine its validity has NOT been a formal method of inquiry throughout human history. Although processes of "trial and error" in solving mechanical problems almost necessitate at least an unconscious 'scientific' process, explanations of how the world IS, or why it is THIS WAY, were promoted by philosophers long before the tool of science developed. A very brief overview of the birth of science, as it relates to the study and explanation of life, is therefore important and instructive for understanding why Darwin's ideas were both revolutionary and yet - in some sense - historically anticipated.

A. The Greeks

1. Hippocrates (450-377 bc): He valued observation and testing rather than pure logic - "cut-it-open-and-see" - Believed in use and disuse and inheritance of acquired traits; so accepted change within a "family". - Close to an embryological, evolutionary approach, and physicians today honor his philosophy of "first, do no harm" in the Hippocratic Oath.

2. Plato (427-347 bc): Plato was trained in the Pythagorean school, and was more truly a pure philosopher rather than a 'naturalist', per se. As such, he was more impressed by generalizations rather than the vagarities and variation of individual experience; indeed, those variations that are so important to a true understanding of biology.

UNIVERSAL PHILOSOPHY (four dogmas)

- became the bedrock of western civilization for 2000 years! Ernst Mayr, one of the most important biologists of the 20th century, states: "It took more than 2000 years for biology, under the influence of Darwin, to escape the paralyzing grip of essentialism...the rise of modern biology is, in part, the emancipation from Platonic thinking".

3. Aristotle (384-322 bc): Aristotle was the first great philosopher interested in biology. He described 100’s of species and fossils, and he wrote books on anatomy, reproductive biology, and life histories. He was Plato's student and Alexander the Great's tutor. He was more of an empiricist than Plato, using observation (and not reason, alone), to answer some questions about the natural world. Indeed, he is credited with describing the first formal rules of deductive and inductive logic. He believed that knowledge could be discovered from observations (induction), but he did not include an experimental component to his methodology - rather, the evaluation of alternative, "induced" hypotheses was by logical decuctive reasoning, alone. He affirmed the Platonic ideals of a harmonious, static whole, with fixed species created by an "unmoved mover" in an array from simple to complex in a great chain of being (Scala naturae) of increasing perfection.

4. Summary: There is a rather schizoid biological inheritance from the greeks. On one hand, Aristotle and Galen provide much correct (an erroneous) factual knowledge about the natural world, and Aristotle's contributions in logic are the foundations of the scientific method. However, the Platonic essentialism that dominated a philosophy of nature would inhibit consideration of evolutionary ideas, and the emphasis on reason as the ultimate arbiter of truth hindered an experimental approach.

B. The Persians (latinized name used in the west)

1. Ibn al-Haytham (Alhazen) (965-1040): Born in Basra (now in Iraq), he is credited with presenting the first formal process of observation, hypothesis, experimental test using quantification and math, and conclusion. In his major work,Book on Optics (1021), he describes his experiments that falsified the notion that sight is caused by particles that radiate from the eye (as argued by Ptolemy) or radiate from the object (as argued by Aristotle).

2. al-Biruni (973-1048): Born in what is now Uzbekistan, al-Biruni applied a scientific method to new fields, basically inventing the disciplines of comparative sociology (in the study and comparison of cultures) and experimental psychology. His contributions to astronomy are even more profound, as he considered the hypothesis that the earth travels in an ellipse around the sun and spins on its axis daily, and he measured the radius of the Earth 600 years before a correct estimate would be made in the west. His most valuable contributions to the progress of science were his emphatic reliance on precise quantification and repeated observations. He believed that error caused by instrimentation or human error could be compensated for by taking the average of repeated observations.

3. Ibn Sena (Avicenna) (980-1037): Also born in what is now Uzbekistan, Avicenna was a contemporary of al-Biruni and is considered one of the greatest philosophers in history. Although he was closer to Aristotle than al-Biruni, he still felt that Aristotle's philosophy of induction needed the critical element of experimentation to test the conclusions. Avicenna is primarily known for building on the works of Hippocrates, Galen, and Aristotle, making contributions to medicine that were used throughout Europe in the Middle Ages.

4. Summary: The Persians were the first to explicitly describe and study natural phenomena in the language of mathematics. Building on aristotelian ideas of induction and hypothesis formation, the Persians added the critical concept of empirical, quantitative, replicated experimentation to test hypotheses. This is the scientific method.

C. The Middle Ages (476-1400)

1. Constantine the Great (reign 306-337 - First Holy Roman Emperor) - His conversion to Christianity signalled a change in the west from the polytheism of ancient Greece and Rome to monotheism; and the tenets of a single, perfect, static creation meshed well with the dominant Platonic philosophy of essentialism.

2. Thomas Aquinas (1225-1274) - Aquinas presented the most formal logical argument for the existence of God, largely using the teleological argument of design. Events or objects that move towards a goal (have a purpose) a primary cause; Aristotle's "unmoved mover" is Thomas's Christian God. Thomas professed a "natural theology", which suggested that one could come to know more of God by studying "His works" (nature).

3. Summary: The unification of political, religious, and economic power in the Roman-Catholic Church created a monolithic cultural authority that was resistant to alternative views. The Church claimed its inerrant authority from an inerrant Bible, so facts or ideas in conflict with the Bible were at least wrong, and at most heretical; alternative sources of truth and authority (like scientific investigations) were implicit challenges to the power of the church. During this period, however, several western philosopher-theologians like Aquinas and Robert Grosseteste (~1168-1253; translator of Aristotle) and Roger Bacon (1220-1292) read translations of muslim philosophers and exposed the west to the power of Aristotelian logic and experimentation.

D. The Renaissance (1400 to 1700)

1. Cultural Climate: The political and cultural tumult of the Protestant Reformation, the formation of the Church of England, and the development of a merchant class and trade, undermined the hegemony of the Roman-Catholic Church and placed a greater premium on knowledge of mechanics and the physical world. At the same time, the voyages of discovery of Dias (1488) - who rounds the Cape without burning up - and Columbus 1492) revealed new species and lands not described in the Bible. The Roman Inquisitions begun in the 16th century were attempts to maintain control over heretics and their ideas. On February 16, 1600, Italian philospher Giordano Bruno was burned at the stake for heresy - probably due to his persistent promotion of logic, reason, and empiricism as a source of truth, rather than religious authority. His support for the copernican system may also have played a role. Protestants were equally adamant in their beliefs, and John Calvin had Michael Servetus burned at the stake for heresy in 1553.

2. 1543: The publication of two works had a profound impact. Nicolaus Copernicus's De revolutionibus orbium coelestium (On the Revolutions of the Heavenly Spheres) described the heliocentric model of the solar system, opposing the terracentric view supported by both the authority of the ancients (Ptolemy and Aristotle) and the Bible. Interestingly, Copernicus still depended on philosophical preferences over observation - he imagined that the planets travelled in circles, not ellipses, because the circle was a more perfect form. Likewise, Andreas Vesalius's De humani corporis fabrica (On the Fabric of the Human body) was published in 1543. Profitting from the renaissance developments in art and printing, Vesalius was able to include exquisite drawings of dissected cadavers. Through this empirical approach to human anatomy, many errors of the ancients (Galen, in particular) were revealed. In short, as Francis Bacon (1561-1626) concluded, knowledge is incomplete; it is not all found in the Bible or the ancient texts, and new knowledge is discovereable by the process of empirical hypothesis testing.

3. Kepler (1571-1630) and Galileo (1564-1642) were the first great natural philosophers in the west to emphasize and use a mathematical, experimental approach to answer questions about the physical world. Galileo's observations of the moons orbiting Jupiter, and the full phases of Venus (impossible to explain with a Ptolemaic model of the solar system), provide empirical support for the copernican model. Galileo, however, was still wedded to the philosophical imperative that the orbits were perfect circles. Kepler attacked this view with voluminous data collected by he and his mentor, Tycho Brahe. By using elliptical orbits, Kepler was able to fashion the most precise predictive models of planetary orbits available. Galileo was a devout Catholic, but he famously said that the Bible tells a person "how to go to heaven, not how the heavens go". In this, and in his goad to "Measure what is measurable, and make measurable what is not so", he personifies the quantitative scientist. In his Dialogue Concerning the Two Chief World Systems (1632), he publicized the debate over these worldviews. The Roman-Catholic church brought him to trial for heresy, and he was ultimately forced to recant his support for the Copernican model before the Commissary-General of the Inquisition in Rome during 1633. He was ultimately placed under house arrest (confined to his home in Arcetri) for the remainder of his life.

4. Newton (1642-1727): In Newton's Philosophiae Naturalis Principia Mathematica (1687) we see the fulfillment of the scientific method - the formation of testable general theory. Newton constructed a general theoretical model of gravity and motion that became classical mechanics. This theory explained the motion of earthly objects (apples and projectiles falling) and the elliptical path of heavenly bodies. We see the culmination of Aristotle's imperative for both inductive and deductive reasoning - from specific observations one constructs a general hypothesis (inductive reasoning). Now, you use deduction to create a prediction that follows from that hypothesis (IF... THEN...). And of course, you subject your prediction to an experimental test in which falsification is possible. Although other natural philosophers (the term "scientist" was not coined until the 1830's) had been held in high regard by some nations, kings, or patrons, Newton was knighted - signifying the complete cultural acceptance of this new way of examining the physical world.

5. Summary: During this period we see the development and application of the scientific method in the west. The "scientific revolution" had a curious effect on the study of life. Science emancipated physics, astronomy, and chemistry from theology by describing constant, natural, predictive laws and by describing the unchanging nature of elements (alchemy disproven). This confirmed the Platonic views of an unchanging universe created in perfection and left to run like a 'clockwork'. But what about our little corner of the universe? Was the Earth also static from 'the beginning", and just how long ago was that, anyway? Anglican Bishop James Ussher (1581-1656) applied logical rigor to the History of the Earth as revealed in the Bible and counted back the generations, determining that creation began at noon, October 23, 4004 b.c. (For a great book about calendars, read Stephen J. Gould's Questioning the Millenium). Thomas Burnet (~1635-1715) wrote The Sacred Theory of the Earth (1680), an account of earth's history as a literal account of Genesis 1. So, both concluded that the Earth was young, and most natural philosophers also concluded that the species were fixed since their creation.

E. The Enlightment (1700’S)

1. Cultural Climate: The 1700's were a tumultuous century in Europe, punctuated by the industrial revolution, the American Revolution, and the French Revolution. Ideologies were shaken to their foundations, and the promise offered by science and reason and industrial power challenged ideas of socieconomic stasis and authoritarian rule.

2. Natural Theology - Following on the thinking of Aquinas, there was a resurgence of Natural Theology to explicitly consider the theological import and relvance of the new observations made by science. The fundamental assumption was that God made things for a purpose, and that we might understand God's purpose if we more fully describe the creation and its operation. The most explicit reconstruction of these ideas was by theologian William Paley's Natural Theology: or, Evidences of the Existence and Attributes of the Deity, Collected from the Appearances of Nature (1802). Here he provides his teleological argument for the existence of God, using the allegory of the "watchmaker".

a. Carl Linne (1707-1778) - "Linneaus" (he latinized his own name) was the "great cataloguer", and he published the first edition of Systema Naturae in 1735. It wasn't until 1753, however, in Species Plantarum (Plant Species), that he formalized his prcedure for using two names to identify a species - the latin binomen (like Homo sapiens). The first name is the GENUS, and the second is called the 'specific epithet' that describes this species and distinguishes it from other similar species placed in the same genus. Linnaeus also grouped these genera (plural of 'genus') into orders, classes, and kingdoms based on additional morphological similarities. In plants, he relied on similarities in the reproductive structures, as many naturalists accepted that species are kinds that reproduce only with themselves. In the 10th edition of Systema Naturae (1758), he applied this system to all animals, too. The oldest scientific species names used today date from these two works. By the way, the word 'species' is both the singular and plural. There is no 'specie'. FYI. : )

b. Georges Louis Leclerc, Comte de Buffon (1707-1788) Buffon pulbished the first volume of his encyclopedic Histoire Naturelle in 1749. Ernst Mayr considered Buffon to be the foremost biologist of the 18th century, and Mayr wrote "it makes no difference which of the authors of the second half of the 18th century one reads - their discussions are, in the last analysis, merely commentaries on Buffon’s work. Except for Darwin and Aristotle, there has been no other student of organisms who has had as far-reaching an influence." He opposed the notion oif classification; if the species were separately created, then of what use was any classification system? He was aware of possibility of evolution but rejects it:
"Not only the ass and the horse, but also man, the apes, the quadrupeds, and all the animals might be regarded as constituting but a single family... If it were admitted that the ass is of the family of the horse, and different from the horse only because it has varied from the original form, one could equally well say that the ape is of the family of man, that he is a degenerate man, that man and ape have a common origin; that, in fact, all the families, among plants as well as animals, have come from a single stock, and that all the animals are descended from a single animal, from which have sprung in the course of time, as a result of progress or of degeneration, all the other races of animals. For if it were once shown that we are justified in establishing these families; if it were granted that among animals and plants there has been (I do say several species) but even a single one, which has been produced in the course of direct decent from another species; if, for example, it were true that the ass is but a degeneration from the horse - then there would no longer be any limit to the power of nature, and we should not be wrong in supposing that, with sufficient time, she has been able from a single being to derive all the other organized beings. But this is by no means a proper representation of nature. We are assured by the authority of revelation that all animals have participated equally in the grace of direct Creation and that the first pair of every species issued forth fully formed from the hands of the Creator." Histoire Naturelle (1753)

c. Jean Baptiste Pierre Antoine de Monet, Chevalier de Lamarck (1744-1829) - Initially a botanist and tutor to Buffon's son, he became an expert in invertebrates and the mollusc fossils of the Paris Basin. through this work, his initial belief in the fixity of species changed. In his culminating work Philosophie Zoologique (1809), he suggested that species change over time, climbing the Scala Naturae from simple forms to complex. The simplest forms were continuously produced by spontaneous generation, and species did not go extinct - they evolved into more complex forms over long periods of time. In addition to this vertical progression, they could also diverge as a consequence of responding to the environment and passing on the traits they acquired as a result of the action of this environment. Structures that were used in an environment would be elaborated (use and disuse), and then these newly elaborated structures were passed on to offspring (inheritance of acquired traits). Lamarck's evolutionary ideas explained the new observations of fossil diversity and apparent extinction. In Lamarck's mind, extinctions were theologically impossible, because he believed in a complete, harmonious creation by a benevolent creator. Why would a benevolent, purposeful creator let creations go extinct, and wouldn't the loss of some species render the perfection of the initial creation imperfect? For Lamarck, species changing into other species preserved the whole of creation. "May it not be possible that the fossils in question belong to species still existing, but which have changed since that time and have been converted into that similar species that we now actually find?" Lamarck is rightly regarded as the first "biologist" (he was the first to use the term) to propose a true evolutionary hypothesis, and a testable, naturalistic mechanism to explain it. Unfortunately, the mechanism was wrong.

d. Georges Cuvier (1769-1832) - Cuvier was also an intellectual giant in France, and was Lamarck's nemesis. A great anatomist, Cuvier founded the comparative approach in anatomy and also founded vertebrate paleontology. Unlike Lamarck, he believed that extinctions occurred; and he supported this contention by showing that the great mammals of the past (mammoths, giant ground sloths, etc.) had no modern living forms (Cuvier concluded that elephants and mammoths were different species, and mammoths were truly extinct.) In contrast to Lamarck's ideas of gradually changing species responding to their environment, Cuvier promoted the notion that there were period cataclysms ('revolutions') that killed off local faunas and required repopulation from elsewhere. This idea became known as 'catastrophism', and stood in opposition to the 'uniformitarianism' of gradual change espoused by Lamarck and others. Cuvier also tore down the notion of the scala naturae, replacing it with four 'embranchments' of life disconnected from eachother. Finally, Cuvier said that the intermediates predicted by Lamarck's gradualistic evolutionary model did not exist, and he reminded the scientific community that spontaneous generation had been refuted (for insects, at least) since the experiments of Francesco Redi in 1668! He was a true essentialist, seeing discontinuity through time and through taxa. Cuvier outlived Lamarck and continued to lambast him and his ideas. Evolutionary ideas fell into disfavor as a consequence.

II. Darwin's Contributions

A. Overview:

One of the great ironies of science is that the two greatest contributions in biology - the theory of evolution and the mechanistic principles of heredity - were described independently of one another within a ten year period. It is ironic because genetics (heredity) and evolution are so critically and intimately related...heredity describes how genetic information is passed from parent to offspring. This creates relatedness patterns within families, within species among populations, and among species. These relationships are a focus of evolutionary studies. The publications marking their official, orthodox ‘births’ were published only six years apart: Origin of Species (1859), and Experiments in Plant Hybridization (1865), yet it was nearly 80 years before these ideas were placed in their proper context within the Modern Synthetic Theory of evolution. In the first part of this course, we will examine these contributions in a historical context. We will also briefly describe the cellular context in which the genetic system operates.

1. Darwin's Life

- born Feb 12, 1809, into a wealthy and distinguished family
- graduated Cambridge intending to join the clergy and study nature as a natural theologian
- 1831-36: Naturalist aboard the H.M.S. Beagle
- 1859 - Publishes "The Origin of Species", which he revises through six editions during his life
- dies April 19, 1882; interred in Westminster Abbey at the feet of Newton.

2. The Origin of Species (1859)

Darwin did three things in this book:

    a. He summarized the evidence for evolution (common descent) as an historical fact
    b. He proposed mechanistic theories explaining ‘how’ evolution might occur (Natural Selection, use and disuse)
    c. He addressed the major problems with his ideas; notably the ideas of apparent design (Paley), the discontinuity of the fossil record (Cuvier), and the source of observed variation.

B. His Argument - Evidence for Common Descent as Historical Fact

1. Geology    

a. James Hutton (1726-1797): Hutton was the first great british geologist. He compared Hadrian's wall - which looks new but was 1600 years old (122 AD) - with natural rock outcrops that were strongly weathered. Hutton concluded that the natural outcrops must be 100's of times older. He also examined an important formation at Siccar Point, where one series of nearly vertical strata is overlain by another series of horizontal strata. This is now called an 'unconformity', and Hutton explained it as follows. Based on Steno's laws of superposition, the bottom vertical sediments must have been laid down first, and they must have been laid down horizontally. Ages must have passed between each deposit, as each turned to rock. Then, uplifts must have occurred to bend them into a vertical aspect. Long periods of erosion must take place to wear that uplift flat, followed by the long intervals of time needed to deposit the second horizontal series. Also, if erosion and deposition acted slowly (as current observations show), then it must have taken a really long time to erode mountains or build up marine deposits (White Cliffs of Dover). He concluded that this slow, 'uniformitarian' cycle of deposition, uplift, erosion, and deposition meant that the Earth was unfathomably old. Indeed, the cycle may mean that it's age might not be discoverable. In short, Hutton concludes, the Earth has "no vestige of a beginning, no prospect of an end."

b. Charles Lyell (1797-1895): Lyell promoted Hutton's ideas of a great age to the Earth and uniform rates of change - making inferences based on the assumption of constant rates of physical processes.  Small changes, accumulating over a long time, could have big effects.  Lyell's three volume work Principles of Geology (1830-33) opened Darwin's eyes as he read them on the H.M.S. Beagle. Geology opened "deep time".... the Earth was at least 100's of thousands of years old, and natural processes working slowly, gradually, and cumulatively through time could affect large changes. Lyell was Darwin's contemporary and personal friend, although he was distressed by Darwin's evolutionary ideas.

2. Paleontology

Paleontology provided a variety of interesting patterns. First, there were extinct forms that were different from the species alive today. Although some earlier natural philosophers suggested that the creatures might still exist in some unexplored corner of the globe, that was a less satisfying hypothesis in the mid-1800's... most areas of the globe had been visited by Europeans. Also, the idea of extinction was repugnant to some people on theological grounds. If God had created a perfect world, then extinction renders that creation imperfect. Also, if species could go extinct since the creation, could species also come into existence since the creation? Just how dynamic was this system?

Darwin was impressed by two major patterns in the fossil record.

1. The major groups of animals accumulate in an orderly manner'. Everything is not represented at the beginning. In vertebrates, for instance, the fishes appear first, and exist throughout the rest of the record. Amphibians appear next, followed by reptiles, mammals, and birds. So it is not everything at the beginning, and it is not a replacement. Where did mammals come from? Spontaneous generation had been refuted, so Darwin knew that mammals had to come from other pre-existing animals. But the only completely terrestrial vertebrates before mammals were reptiles.

2. A second major pattern occurred within some lineages of similar organisms. Within some lineages, we seen orderly change in the size or characteristics of species in a geological sequence. For instance, consider the morphological patterns in a particular taxon (horses). Fossils in a stratigraphic sequence are similar, but often have traits that form a continuum...like the progressive loss of digits on the horse limb. And, with each innovation, there are often radiations - a "spurt" in the number of species that show this new trait. And finally, these species in recent strat are more similar to living ('extant') species than the species found in deeper, older strata. So, many of these transitional sequences terminate in living representatives.

3. Comparative Anatomy

a. Homologous Structures
    Although having a different outward "look" and although used for different purposes, they have an underlying similarity in structure - forelimbs of vertebrates all have one long upper arm bone, two lower arm bones, a bunch of wrist bones, and five digits. Darwin saw the similarity in structure as important. An engineer builds different things for different purposes - cars, boats, and airplanes are structurally DIFFERENT. Here, however, it seemed as if one basic structure was modified for different uses. Darwin knew why siblings in a family were similar - they had the same parents (ancestors). He reasoned that these structural similarities in different species might be due to the same principle - common ancestry. Also, he observed a correlation: Different uses correlated with different environments. Could this correlation be causal?

b. Analogous Structures
    Organisms in the same environment often have a similar outward structure or body plan. For example, flying animals all have an aerodynamic wing that is wider at the front than at the rear. However, the wings of differnt animals are differnt in underlying structure. Bats have fingers that support the membraneous wing, whereas birds lack fingers and the body of the wing consists of feathers. Insect wings don't involve the limbs at all (even though they have 6!). Again, Darwin observed this correlation with the environment: similar use (and outward structure) in similar environments. Could this correlation be causal?

c. Vestigial Organs
   These are organs that have no function in one organism (where they are 'vestigial') but they do function in other organisms. So, some whales have hip bones, but no legs. Why do they have these bones? Darwin was struck by the IMPERFECTIONS in nature, as much as the adaptations. Why do men have nipples? Why do we have muscles that wiggle our ears? Why do we have strong muscles in the front of our stomach, which are not "load-bearing", and weak muscles at the base of our abdomen (which rupture in a hernia)? This is a reasonable relationship in a quadraped, but not in a biped. Why do we have tail bones, but no external tail? Again, these are NOT well-designed features. In fact, attributing these imperfect designs to a perfect creator could be interpreted as heretical.  However, when we see them working in OTHER species, it suggests that maybe we inherited them from common ancestors where they DID serve a function. As a scientist, Darwin was trying to explain ALL the data (adaptations and imperfections), he was not simply bringing forward only the data that supported a preferred position (design).

d. Embryology
Embryology reveals homologies and vestigial structures in both the anatomy of embryos and the process of their development. For Darwin, the notion that very different vertebrates, such as fish, amphibians, reptiles, birds, and mammals, would develop from very similar initial forms was inexplicable from a 'separate creation' perspective. For example, why do whale embryos (like the one pictured to the right) have hind limb buds? Why do all vertebrates have folds of tissue in the neck, when only fish develop them into functional gill slits in the adult? Some anomalies like the recurrent laryngeal nerves of mammals (described in your book) are explicable in a developmental, comparative, evolutionary context. Although no modern evolutionary biologist propounds the notion that an organism "traces their evolutionary history" as they develop from an egg (this was Haeckel's post-Darwinian idea that "ontogeny recapitulates phylogeny"), and Haeckel's drawings grossly exaggerated the similarities among vertebrate embryos, embryos are far more similar to one another than adults, and embryos are more similar to other embryos than they are to their own adult form. As we will see when we look at modern contributions from genetics and developmental biology, the similarities in development are even more dramatic than anatomy alone suggests.
 

STUDY QUESTIONS:

1. Draw the cell cycle, labeling each stage and highlighting the main event in each stage.

2. Draw a chromsome before and after replication.

3. What enzyme begins the process of DNA replication?

6. Draw a cell with 4 chromosomes in each stage of mitosis.

7.  What is Platonic essentialism (or 'idealism') and how did it hinder the consideration of evolutionary ideas?

8. What contribution did ancient Persians make to the development of the scientific method?

9. What contributions did Copernicus, Kepler, Galileo, and Newton make to our understanding of the solar system? Frame these in the context of the scientific method.

10. What counter-intuitive effect did the renaissance have on the development of modern (evolutionary) biology?

11. Why did Buffon criticize the classification system of Linnaeus, which put species in groups?

12. How did Lamarck explain the loss of particular fossil species (extinction) through time?

13. What is the principle of Natural Theology, as professed by Aquinas and Paley?

14. What observations did Hutton make, and what did he conclude from these observations?

15. What two patterns occur in the fossil record that impress Darwin regarding the hypothesis of evolution and common descent?

16. What are homologous structures?  What correlations occurs with the environment?

17. What are analogous structures?  What correlation occurs with the environment?

18. What are vestigial structures, and why were they so important to Darwin's refutation of Paley?