Wednesday, August 1, 2007

Searchable Origin


Check this out...


In case you don't own a copy of the most important book in the history of biological science for yourself, you are in luck. The Literature Network has posted over 1,900 stories, poems, novels and other books online for all to read, free of charge, in a searchable format. Click here to search the Origin of Species (1859).

Tuesday, July 31, 2007

Evolutionary Mechanisms: Natural Selection & Mutation

No mutation, no novel heritable variation. No variation, no adaptation. No variation, no evolution. No evolution, no biodiversity. No biodiversity: priceless.

All scientists must take sides. Everything in science is an argument or an inquiry. Every scientific study makes claims about the natural world (gathered by the author or not), and it is the duty of scientists to present and interpret her findings via manuscripts, posters, talks, and other forms of sometimes public outreach. In communicating scientific ideas, scientists invariably argue for different perspectives on the significance and meaning of their findings, and their relationship to the rest of science, including the closely related work of others. Darwin's major scientific work, the Origin, represented/represents a synergistic volume condensing masses of primary scientific discoveries and arguments, including some speculations (what makes science writing exciting!), into one BIG argument for organic evolution by natural selection. His postulates were as follows,

(p1) There is variation in nature,

(p2) Varitions get passed from parents to offspring, from one generation to the next (though Darwin did not have modern genetics to understand how this is accomplished; he supported an idea of genetic "blending"),

(p3) In each generation, more offspring are produced than can survive, and mortality is non-random, with the most "fit" offspring being those having heritable traits making them capable of withstanding environmental changes, survive and reproduce in that environment, thus pass their heritable variations to the next generation,

(C) Therefore, the traits of species are naturally selected to fit the changing environment through time.

This is the argument for natural selection, descent with modification by non-random mortality due to differential fitness of heritable genotypic/phenotypic variation. From the argument, it is clear evolution proceeds in a non-random, not-by-chance fashion antithetical to common misconceptions. Also, this is a testable set of ideas which has yielded empirical research on natural selection both in the laboratory and in nature. As important as this argument may be, there are several other mechanisms of evolution (i.e. mutation, migration, genetic drift), and we will leave natural selection to discuss an arguably more fundamental mechanism of evolutionary change played on in the introductory sketch, mutation.

Genetic Mutation

We have discussed previously how independent assortment of alleles into our gametes combined with proabilities of chance associated with fertilization in diploid, sexually reproducing organisms is capable of introducing genetic variation in natural populations. But this occurs without mutation per se.

Mutation is the ultimate source of new genetic information, information necessary for different evolutionary mechanisms to effect evolutionary change through time. Therefore, it is important we recognize chromosomal and lower level sources of genetic mutation as the actual material evolutionary forces work with, for and against. Central questions to guide this discussion might be, what are mutations, how do they happen, at what rate do they occur, and what are their consequences in individuals and populations?

Recall the central dogma of molecular biology states that DNA is transcribed into mRNA (inside the nucleus), which is translated into amino acid sequences of proteins by ribosomes through specific biochemical interactions in the cytosol. The discovery of nucleic acids, these patterns, their mechanisms and implications has led to the following definitions, which get us off to a good start: mutation is any change in the nitrogenous base sequence of DNA, genes are sequences of DNA that code for particular proteins, loci are the physical molecular "addresses" of genes along the sequence of an organism's hereditary material, and alleles are versions of genes coding for the same protein but having different sequences of DNA (than the "wild type"). That said, there are multiple types of mutations in nature.

Some genetic variation stems from the chromosomal basis of inheritance and associated mutations, which we have also touched on elsewhere. Meiotic synapsis and crossing can over lead to different arrangements of genes on chromosomes. This is not only a source of new mutation, but a source of whole new genes! How? Whenever chromosomes are unequally paired (physically out of alignment) by the synaptonemal complex, crossing over can duplicate copies of genes. These extra copies are very important, because they may mutate and differ in their function at later points in time, creating new genes. Also, sections of chromosomes sometimes jump from one homologous pair to another (e.g. chromosomal translocation), and whole pieces of chromosomes may rearrange spontaneously in our cells (e.g. chromosomal inversion). These chromosomal changes alter DNA sequences at large scales and may lead to terrible disease in individuals (e.g. Down syndrome, Klinefelter syndrome, and Turner syndrome in humans).

Genetic mutation at the most basic units of DNA, base pairs, represent the most physically restricted and specific units of genetic mutation. These can be classified into different groups. When single base pairs (A,C,G,T) are substituted one for another, point mutations are said to occur. When DNA replicates itself during the cell cycle (S phase), chemical changes in base pairs are relatively frequent. Fortunately, vertebrate DNA replication machinery also has a repair mechanism for such cases. When DNA repair fails, point mutations result where, for example, an A may be left in place of a G. There are two different classes of point mutations, (1) transitions, where pyrimidines are substituted for pyrimidines and purines are substituted for purines and (2) transversions, where pyrimidines are substituted for purines and vice versa. Evidence suggests transitions are far more likely in nature (2:1 or 3:1; thus phylogenetic studies of DNA sequence information often give different statistical weights to transitions and transversions). An important question for you might be, how do I remember which changes are transitions vs. transversions? Well, adenine and guanine are purines and cytosine and thymine are pyrimidines. Perhaps, you can remember, as I do, that the ancient Egyptians built the PYRamids and also are reknown for domesticating and worshiping Felis catus / Felis silvestris catus (domestic cat/house cat). It's true!.

The effect of point mutations is also dichotomous. Because transcribed DNA takes the form of mRNA, whose three-base-pair sequences called codons code for different amino acid additions during translation, point mutations change the composition of codons. These changes may or may not result in changes in amino acid sequences of proteins; respectively, these changes are referred to as nonsynonymous (a.k.a. replacement) substitutions and synonymous (a.k.a. silent site) substitutions. However, whether point mutations are synonymous or nonsynonymous, they always produce new alleles, therefore mutation.

As the modern synthesis developed in the early twentieth century, a classical group of geneticists suspected the genetic variation in nature was marginal, with natural selection weeding out useless mutations such that only the most fit genes survived the test of time. Modern genetic research, however, has confirmed the opposite is true. There turns out to be much more genetic variation in nature than early geneticists thought. In fact, the evidence shows that mutation rates, on a per genome per generation basis, are similar across many different kinds of taxa and highly influenced by the number of cell divisions before reproduction. Organisms with longer generation times, with longer lives and longer periods of cell growth and division between reproductive events, tend to display higher rates of genetic mutation. Taking the number of cell divisions into account, we find out living things have even more similar (but high) mutation rates. Each individual in mammalian populations harbors unique genetic mutations based on experiments involving simple, obvious phenotypes. Imagine how much more genetic variation is present, yet undetected, as silent site mutations and other kinds of covert genome duplication and rearrangement!

Despite the great amount of mutation thus variation present in natural populations, mutations are also rare in the sense that many mutations come from slips in the DNA replication and repair machinery, which turn out to be incredibly accurate.

The field of molecular genetics is divided in controversy over answering the question, "Why are populations are genetically diverse?" On the one hand, the balance or selectionist school of thought claims that natural selection is a major force driving the diversity of populations because selection favors mutant individuals with rare traits in changing or novel environments. On the other hand, the neutral theorists make a very convincing claim that most mutations are functionally and selectively equivalent (and deleterious), and that the natural world is genetically diverse because selection fails to get rid of them, to cut them from the team, prune them from the tree, so to speak. ~ JB

Sunday, July 22, 2007

Darwin to Central Dogma: How We Get Protein from the Genetic Code. Part II

So, let's talk about the Central Dogma and start by moving beyond the introductory material to the meat of the subject in this, the second part of this series.

Transcription

As you can see from the first (left) overview figure in Part I, the molecular pathways of genetic information, which are analogous to strings of letters (nucleotide or amino acid alphabets) forming different kinds of sentences in different kinds of languages, transform this information from DNA or RNA to protein, but never really from protein to nucleic acid. Transcription is the name given to transferrence of DNA "sentences" into RNA "sentences;" in turn, these code for specific amino acids in polypeptide chains (on several occasions this code is redundant, more later).




Where do we begin understanding this process of gene to protein, transcription and translation? With the source, DNA. But first, we must define some terms.




DNA stands for deoxyribonucleic acid (structural model at left) and is found in pro- and eu-karyotic cells. Each DNA molecule is comprised of many smaller molecules linked together in a long, double stranded helical chain. Eukaryotic DNA (our focus) is linear, while DNA is often in a ringed or looped form with no loose ends in prokaryotic cells. The smaller molecules (monomers) that make up DNA are called nucleotides, and in DNA these come in four basic forms, A, C, G, and T, which stand for adenine, cytosine, guanine, and thymine. DNA monomers are grouped into two different categories, purines and pyramidines; however, they all consist of the same basic structure, being composed of a nitrogenous base, a deoxyribose (five-carbon, or pentose) sugar, and a phosphate region.


RNA, or ribonucleic acid, is also linear and found in eukaryotic and prokaryotic cells. The structure of its monomers are similar to those of DNA, except the sugar group contains the oxygen-containing side chain DNA is missing (hence the name "deoxy-" ribose)--or, plainly, regular ribose is incorporated into RNA monomers. In RNA molecules (polymers), the "alphabet" of the RNA strands ("sentences") is similar to that for DNA, with one exception; uracil (U) is used instead of thymine. Last, but not least, proteins are polymers of amino acids, organic compounds containing carboxyl and amino side chains off a carbon backbone.



Now, transcription.


One form of RNA, called messenger RNA (mRNA), is the runner mediating DNA-protein synthesizing compound information flow. So information doesn't just go from DNA to RNA to protein; it goes from DNA to mRNA first. This is accomplished by a series of specific transcription steps--promotion, factor addition, transcription, and termination--with a similar general form in eukaryotes and prokaryotes; however, the mode of operation differs between the two groups in terms of how transcription is stopped. Before describing this difference, I will describe the similarities in transcription processes.



Transcription, like DNA replication, is carried out by a special enzyme, RNA polymerase. There are several types of RNA polymerases (RNAPs) in eukaryotic cells, called RNAP I, RNAP II, and RNAP III. RNAP II carries out transcription of DNA into mRNA. Furthermore, only certain regions of DNA are transcribed. How? DNA sequences contain segments known as "promoters" that signal RNAP II (sometimes called Pol II) to begin transcription of the "downstream" DNA (5'-->3'), a specific set of nucleotides called the transcription unit.



The promoter region contains a "TATA box," a TATA sequence around 25 nucleotides from the beginning of the transcription unit (transcribed DNA strand). Successful transcription requires a group of transcription factors binding to DNA before RNAP II can start working. Once this event takes place, RNAP II comes in and binds the DNA strand with these other molecules, the double helix is unwound, RNAP II begins putting together RNA molecules with one strand of the DNA double helix (the template strand) to form the mRNA product, or mRNA transcript.



Now for the differences in pro- and eukaryotic organisms... RNAP II (aka Pol II) continues working downstream along the DNA template, matching nucleotides to the template and elongating the mRNA transcript. However, at the end of the transcription unit, the process has one of either (at least) two fates, which are dependent upon which type of organism transcription is occurring in. When RNA polymerase reaches the end of the template DNA in, say, bacteria, for instance, a termination sequence of nucleotides signals polymerase to pop off of the DNA molecule and transcription is halted. On the contrary, wen RNA polymerase II reaches the end of the transcription unit in humans, for example, a special polyadenylation sequence, AAUAAA, signals nearby proteins to clip off the mRNA transcript, while the polymerase keeps chugging along until it basically (oddly) falls right off the DNA molecule. All of this takes place in the nucleus, with great speed and great precision!




Click here to see an activeX movie of transcription!!!!




RNA processing



You may assume the first mRNA transcript is the one that gets translated into protein. Directly from the DNA, baby. This is a nice story, except for the fact that this isn't what really happens! What really happens is, the first mRNA transcript is actually the pre-mRNA. It must first be manipulated by proteins in the nucleus before shipping to the extra-nuclear cytosol where it will direct protein synthesis. So, what exactly does this processing entail? What makes this process different from transcription in other life forms, say prokaryotes?



Messenger RNA is manipulated at both ends during processing. At the 5' end, a phosphorylated guanine nucleotide is added, called the 5' cap. At the other, 3' end of the mRNA transcript, the poly-A tail is added just beyond the polyadenylation sequence (AAUAAA, just mentioned). The new 3' end consists of a repeat of 50-250 A's. These end modifications aid in extra-nuclear transport, ribosome attachment, and protection of the fledgling transcript from hydrolysis. So, from left to right, the mRNA is composed of the 5' cap, the mRNA regions, and the poly-A tail. Within the main body of the mRNA, however, some regions of nucleic acid are fated for near-future translation, while others represent untranslated regions, or UTRs. Protein-coding segments of mRNA are signaled at each end by start (AUG) and stop codons (UAA, UGA, UAG). Codons, in turn, are three-nucleotide groups read by protein synthesis machinery, which play a pivotal role in translation of mRNA to polypeptide chains, which we turn our attention toward in just a moment, after discussing the most bizarre part of mRNA processing, RNA splicing.



UTRs contain regions of nucleic acid sequence that are not expressed, called intervening sequences, or introns. Conversely, translated regions of mRNA include exons, expressed regions of genetic material which influence protein synthesis. RNA splicing is the term given to the portion of mRNA processing that splices introns out of mRNA transcripts. So, we see that pre-mRNAs contain 5' caps, UTRs, TRs, polyadenylation signals, and poly-A tails, with UTRs containing introns and TRs containing exons! Hard to keep track of all that right? That's just the way it is. After RNA processing is completed, including RNA splicing (which I forgot to mention is carried out by enzymes called spliceosomes), the mature mRNA transcript is more simplex, consisting of a 5' cap, short UTR, TR or coding region, another short UTR, and the poly-A tail.



So, this begs the question, "If machinery [spliceosomes] is in place to remove UTR segments called introns, isn't this disadvantageous, a waste of energy? Why hasn't evolution selected against intron survival in animal genomes, when this seems to be the most parsimonious modus operundi?" Brilliant. Recent inquiry has shed a great deal of light on this subject, and it appears that introns are in place for a non-random reason. Instead of representing a random, useless, or vestigal process/pattern introns remain in eukaryotic genomes because they help get mRNA transcripts out of the nucleus, but also for a more important reason. Some gene regions may be treated by translational machinery as introns or exons for different reasons; in turn, this leads to differential RNA splicing called "alternative RNA splicing," which confers upon single genes the ability to code for more than one protein. In effect, a consequence of alternative RNA splicing is that genomes can generate a far greater volume of protein products per unit nucleotide length. Also, equally important is the idea of exon shuffling, which says that introns spacing exons provide more length of genome (albeit non-coding length), increasing the probability that crossover events will rearrange exon ordering while maintaining the coding sequences to give rise to new sets of exons (mutant alleles) giving rise to new proteins, giving natural selection more material to work with!!



Translation




Good public speakers often give the advice to begin with an overview, a roadmap for the content to follow, but to guard your secrets for "money slides" that come later, say in a powerpoint. I'm skipping that advice on the translation part here. Why? Translation is so simple, it would waste your time to overview. So what does it entail? Translation is the process of transferring molecular genetic information from processed mRNA to amino acid chains. Translation is accomplished by transfer RNA (tRNA) and ribosomes and involves three steps: (1) attachment of mRNA to ribosomal subunits and proteins and intitiation of amino acid chain translation; attachment of tRNAs to mRNA using anticodon sequence regions, and ribosome addition of tRNA amino acids to the lengthening polypeptide chain; and termination of the translation process.

Now, you realize there are multiple types of RNA molecules. It is also important to realize physically what this process of translation entails, which requires knowing something extra about the RNA and proteins involved. RNA, as you know, is single-stranded nucleic acid in composition. Also, RNA doesn't form helical arrangements like DNA. However, RNA does not take the simple form of linearity suggested by textbook cartoons and the fact that it is single-stranded; instead, RNA molecules fold into complex structures called hairpin loops based on pairings of nucleotides from different regions of the strand. Transfer RNA is no different in this respect. While often depicted in simple two-dimensional form, tRNA has a complex and specific three-dimensional structure with four nucleotide base-pair regions and three loops of exposed nucleotides. At the 3' end of each tRNA is an amino acid attachment site. One nucleotide loop contains a three base sequence called the anticodon.

Translation requires tRNA processing before normal progress can be made, just like mRNA transcripts require processing before joining in the translation equation. While mRNA (and other types of RNAs) are processed in the nucleus, it is in the cytosol that amino acids (AAs) are "activated," or joined to free tRNAs, by enzymes called aminoacyl-tRNA synthetase, producing the processed tRNA product called an aminoacyl tRNA or activated tRNA. Aminoacyl-tRNA synthetase enzymes have active sites for amino acids and tRNAs and catalyze reactions attaching the two molecules through covalent bond formation. The addition of amino acids to aminoacyl-tRNA synthetase is energetically expensive, costing cells energy in the form of ATP floating in the cytosol. After AAs and tRNAs are joined, the finished product pops out of the aminoacyl-tRNA synthetase active site and into the cytosol, where the new complex is available to the translation machinery. An important point is that each tRNA must bind with a specific AA; therefore, because there are 20 types of eukaryotic amino acids, the animal cell contains 20 different types of these synthetases, one for generating each aminoacyl tRNA necessary for translation of mRNA phrases into analogous phrases in the amino acid language.

So, enough of this background already! What about the act of translation, how complex is that? Biochemically, very complex. Generally, easy to remember with some practice.

Let's look at this in terms of materials and methods. Materials required for translation include small and large subunits of ribosomal RNA that make up ribosomes, aminoacyl tRNAs, mRNA transcripts, GTP, and a host of protein binding and release factors that guide the translational processes at the surface of the ribosome. Now, the method.

During the initiation phase of translation, the small ribosomal subunit (ribosomal RNA made in the nucleolus and associated protein) binds, along with the initiator tRNA (containing the anticodon of the mRNA start codon), to an mRNA transcript. The initiator tRNA is an aminoacyl tRNA with a methionine amino acid group attached and an anticodon sequence of UAC, which makes it possible for this initial tRNA to bind the start codon, AUG by joining bases with hydrogen bonds. After this complex is formed, a large ribosomal subunit moves in opposite the small subunit and GTP is hydrolyzed to provide energy fueling the attachment of the initiator tRNA to a special site (fold) on the large ribosomal subunit. Note, there are three dfferent sites on the large ribosomal subunit, called the A site, P site, and E site. The initiator tRNA binds to the P site as a result of this energy input. That's the end of initiation.

The translational elongation phase is exactly what the name implies. As in mRNA trascription, the elongation phase of translation represents the expansion of the polymer product, in this case an amino acid chain. At the end of the initiation phase, both ribosomal subunits, the methionine aminoacyl tRNA, and the mRNA transcript are bound together with several protein complexes. Elongation is set up because the A and E sites of the large ribosomal subunit are exposed. Elongation is a cyclic process involving the following steps: (a) binding of an incoming aminoacyl tRNA to the A site, (b) attachment of the polypeptide initiator (methionine, or the last amino acid added) to the next amino acid at the tip of the just arrived activated tRNA (set into the A site in step a), (c) shifting tRNAs over one site to the left (see figure below paragraph), which moves the chain-containing tRNA to the P site and the original tRNA to the E, or "exit, site, from which point it pops off the ribosome. This three-step process is carried out, moving the mRNA transcript 5' to 3' through a nook in the ribosome, and continues until the ribosome falls off the mRNA molecule.


Translation is terminated when the codon just before the stop codon is translated into amino acid, such that the stop codon is the next available in the A site. A protein release factor steps into the A site, hydrolyzing the bond between the tRNA holding the AA chain at its end (in the P site) and the AA chain itself, causing the two to separate and the whole translation assembly to disassociate into its respective parts. And that's it!

Significance

Understanding how genetic information is shuttled at the molecular level from DNA to proteins is the foundation of molecular biology and an integrative area of impactful research with implications for evolution, development, and world health. The structural complexity of the ribosomal machinery alone has taken over forty years to decipher. Just last year, the 2006 Nobel Prize in Chemistry was awarded to Roger Kornberg of Stanford University for his study of how DNA is transcribed into mRNA, which has yielded stunning crystallographic and digital images of all the biochemical factors involved in this process (see this link and this link).

Studies of transcription and translation are medically important, especially from the perspective of pharmaceutical applications. For example, transcription studies have led to the development of drugs capable of halting bacterial transcription, including streptomycin, which are useful for fighting human bacterial infections and associated diseases.

Last, but not least, transcription and translation, in essence the arrows in the Central Dogma of Molecular biology overview figure from Part I, matter to our understanding of evolutionary processes and evolutionary biology, its applied and pure scientific frontiers. As I have explained in Part I, neither Darwin nor his contemporaries had access to a robust field of genetics as we do today. Darwin's cousin, Francis Galton, was one of the leading scientists in proto-genetic studies during their lifetimes and his interests and those of other scientists lacked the Mendelian focus that gave rise to so much greater an understanding of heredity in the 20th Century, leading to the Central Dogma. Had these men (and maybe some women scientists of their day, if they existed) known what we know now, theirs would be our more fully-orbed view of evolution. Evolution cannot happen without starting material (origins of life, not our concern), without life itself. More importantly, however, evolution could not have given (and continue giving) rise to the tremendous diversity of life we now see around us without genetic variation, a product of errors in processes incorporated into the Central Dogma.

In other words, no mutation means no evolution, and mutations arise due to slips in DNA replication, mRNA transcription, amino acid translation, and expression regulating processes. Without transcription and translation, hereditary information could not be transformed into the structural and functional complexity of living things. Alternatively, living things could not evolve, could not flourish with modification, without stochastic changes in the hereditary information and its flow through biological organisms. More on evolution and mutation next time. Later. ~ JB

Follow this link to information about translation and the Nobel Prize.

Saturday, July 21, 2007

Darwin to Central Dogma: How We Get Protein from the Genetic Code. Part I

Once upon a time, a wise man said, "Timing is everything." A major difficulty of Darwin's theory of organic evolution by natural selection (1859), as revolutionary as it has been, resulted from the timing of his life and work. Don't get me wrong, Darwin's theory came at a crucial point in the development of modern science and was only made possible by the discoveries just preceding his work. But it was constrained by the ignorance and interests of the scientific community of its day.


Darwin constructed a theory that explained how natural environmental forces and interactions shaped the evolution of heritable traits in a non-random fashion, giving a mechanism responsible for the design and diversity found in the natural world. Based on systematics, geology, developmental embryology, biogeography, popluation studies and a host of other evidence, Darwin devised the unifying theory of biology, no bones about it. What he lacked, however, was a robust theory of how these traits were passed from one generation to the next. Enter: the biologists' favorite monk.


Gregor Mendel was a Moravian monk. His birthday was July 20, 1822. His alma mater was the University of Vienna. Mendel was a contemporary of Darwin's credited with conducting rigorous scientific inquiry into plant hybridization incorporating experimentation and statistics (probability theory). Mendel worked out two simple theories of inheritance that form the basis of modern genetics: (a) the theory of segregation and (b) the theory of independent assortment of alleles. Around 1865, Mendel published a few papers on his inheritance work. Mendel owned a copy of Darwin's Origin, and it is thought his writing reflects a Darwinian influence in some passages; conversely, Darwin was also familiar with Mendel's work although he did not possess copies of Mendel's few papers. Had not Mendel substituted activism and religious duties for his scientific research a short time after his publications, his findings might have been acknowledged. Instead, his work was never fully appreciated until after his death, when several scientists rediscovered and redistributed his papers and quickly developed a modern theory of inheritance based upon them.


Modern advances in statistical analyses and population genetics based on Mendelian inheritance theory were merged with Darwin's theory in the early 20th Century in what is now known as the "Modern Synthesis" of evolutionary thought. Key players in this synthesis included biostatisticians, early geneticists, population biologists such as Morgan, Mayr, Fisher, Wright, Simpson, Haldane, et cetera. As genetics developed, it became understood that variation in heritable traits were the result of genetic variation due to gene mutation at the chromosomal level, then the molecular level as DNA was established as semi-conservatively replicated genetic material by Hershey, Chase, Watson, Crick, Franklin, Meselson, Stahl, and others.


Meanwhile, since the 1930s, studies of biochemical metabolism and biosynthesis had been laying the foundation for uncovering what Francis Crick would later call the "Central Dogma of Molecular Biology." This discovery had its origins in a theory that single genes directed the synthesis of individual enzymes responsible for key biological functions as players in biochemical pathways. In the modern era, Crick and others empirically tested this hypothesis and revealed the answer to how phenotypes, in the form of proteins, arise from specific sequences of DNA, or genotypes. The Central Dogma states that DNA, sequences of nucleic acids, is transcribed into RNA, which is then translated into proteins, sequences of amino acids. These proteins may be enzymatic or non-enzymatic; regardless, they influence the function of living things from cellular to organismal levels.


But how does this happen? How does "biological information" get transferred?


Overview Figures:











DNA transcription


(in depth look at processes starts in Part 2)

Monday, July 16, 2007

Sex, Lies, and ... Meiosis

Continuing my theme on "10 Things Every Biology Student Should Know," what is meiosis and, considering it may be a boring topic for most, why is it of interest from a Darwinian view of life? That's where we're going. In the process, we'll talk about sex and lies, no doubt.




Many living things lead sexual life styles. Although there are several different types of sexual modes of operation, as those in some plants and fungi, we will focus on sexual life cycles in animals, including humans ("We're all sexual people, with so much love to give" - Marvin Gaye). Homo sapiens and other vertebrates are physiologically made up of many, many millions of somatic cells. These comprise most of the body and are not passed directly to offspring. Another set of cells, termed the germline, is comprised of all gamete cells and gamete-producing cells from gamete to zygote and back (Fig. 1).






Figure 1. This diagram reveals the "dead end" nature of somatic cell lines in relation to the theoretically eternal germline (reference).



After fertilization, some of our cells go on to specialize in gamete (sperm or egg) generation. These are located in the male testis and female ovary. This is not a new concept. However, as Fig. 1 points out, it is important students of biology realize somatic cells are never passed on from one generation to the next under normal conditions (e.g., barring mutation of somatic cells). That's why your liver cells are not inherited from your parents. For the empirical materialist, this is evidence for the idea of the selfish gene, which Richard Dawkins set forth in his book by the same title. Some philosophers use this fact and others about somatic and germ cell lines to make arguments with important implications for not only how we view the world, what we can learn from these facts, but also about applications of this knowledge in medical studies; for example, stem cell research.


So, we have sex, which drives much of the advertising industry and is a major player in people's behavior and a major influence upon American culture (music, clothing, tv shows, language, etc.), which tends to direct the rest of the world's societies for good or bad. The fact of sex does not set us far apart from the many other animals with sexual life cycles. So, we are like animals in this respect. But I'm not going to discuss that claim. A major question that all human beings grapple with is, "Why do we have sex?" In response to this important issue, I am, however, going to make the claim that sexual reproduction is likely to have been conserved for a variety of reasons which only make sense in light of evolution. There are many many reasons--perhaps you can name several from your own experience, even--why sex has negative effects, why sexual life cycles aren't perfect systems.


"What are the negative aspects of sex?" you say. "Why would he say sexual reproduction is a bad way to operate, in the loose sense? What's wrong with the human reproductive system?" Well, among other things, sex consumes a large amount of time, resources, chemical energy, and so on. Also, our plumbing seems a bit off down below, especially for the males of our species, who have all their genetalia dangling out in the environment (necessary because body heat negatively effects sperm production, unnecessary because of other more obvious problems including physical damage). Add to these difficulties associated with obtaining mates (e.g., competition), and it seems sex is an awfully troublesome means of getting the reproduction job done. So what is the evolutionary significance of sex? The answer lies in the chromosomal basis of inheritance and the mechanisms responsible for genetic variation related to meiosis and other genetic processes. I am going to discuss reasons why evolution has selected this modus operandi anyway and will be detailing the way our bodies generate and pass gametes from one generation to the next, with an emphasis on the contrast between mitosis and meiosis.


Meiosis


I have discussed the cell cycle and mitosis at length. Recall, mitosis is the body's means of increasing the number of cells in a living organism and in part this is due to the fact that increasing the surface area of cell connections and maintaining small cell size increases the speed and efficiency of cell signaling, nutrient processing, and cell packaging and shipping of cellular products, et cetera. Mitosis starts with a single diploid cell and generates two copies of the original starting material (roughly exact copies). Our somatic cells undergo lots of mitotic divisions (some of them, others to a lesser extent/rate). So, for every action, there is an equal and opposite reaction. Meiosis is our bodies counter to constant division, because it is the sole means of reducing the body's ploidy number; meiosis reduces chromosome number by generating four haploid cells from a single diploid cell.

Figure 2. Mitosis vs. Meiosis.
Mitosis involves prophase, prometaphase, metaphase, anaphase, telophase and cytokinesis in sequential order. Meiosis involves the same steps, but carries out the phases twofold with a modification of theme. Every time meiosis happens, it happens again for the same daughter cells, generating four haploid cells (Fig. 2, right side).

The main difference between mitosis and meiosis (which is just mitosis X2), is that during metaphase (metaphase I) homologous chromosome pairs line up in tetrads and experience synapsis and crossing over at the center of the cell. In contrast, individual sets of duplicated chromosomes line up during mitotic metaphase. Also, sister chromatids remain connected to one another in meiosis during anaphase I, while during mitosis these are the objects being pulled apart toward different cell poles on microtubule spindles. For the most part, that's it (of course, there are some details we've glossed over). If that's where your high school biology teacher or professor stopped talking or you stopped listening, or if you missed that day of biology class, let me explain the coolest part of this whole idea of chromosome splitting and cell duplication and gamete production.

Darwin and Meiosis

Darwin recognized the importance of heritable variation in nature. He studied natural and artificial phenomena. Then from a diverse set of facts, he contrived a consilient explanation for how this variation is used as raw material for descent with modification, or evolution. However, we are all subject to the ignorances of our times, and Darwin is not immune to this funny little fact about the human condition. There were many things his generation never came to know that we have discovered in the nearly 150 years since his death, a time of rapid scientific and technological progress. For our purposes, the most important of these were the genetic, molecular and chemical mechanisms of inheritance described by geneticists based on the work of that famous monk, Gregor Mendel.

The biodiversity around and within us could not be possible without mechanisms generating diversity, the chief of which is molecular mutation, which comes in many different forms. Aside from mutation, however, other powerful forces shape the genetic variation found in the natural world. Several of these processes have their origin in the statistical ramifications of the physical acts during meiosis, hence resulting from sexual life cycles. Three of these would be independent chromosomal assortment, chiasmata, and randomization of fertilization.

Not only has meiosis aided in the generation of genetic variability in nature, but also it has an evolutionary history of its own. For example, because of genetic differences, human meiosis is more advanced than forms of division found in some insects (Bogdanov 2003). Meiosis and sexual reproduction are thought to have evolved early in evolutionary time in unicellular organisms, and are controlled by hundreds of genes (Bogdanov 2003).

So, you've been no doubt wondering all this time where the "lies" in the title come in, right? Simple. The lie is that meiosis, life cycles, and chromosomal evolution and associated gene expression, regulation, and cellular processes are "boring." That's the lie. In fact, these represent exciting areas of research, even disease research, which are uncovering more and more about an integral process that evolved in some of our most ancient sexual ancestors. Think about that the next time you put on Marvin Gaye or Barry White! ~ JB

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References

Bogdanov, Y. F. 2003. Variation and evolution of meiosis. Russian Journal of Genetics 39:363-381

Thursday, July 12, 2007

TED, war, and the Intelligent Design-evolution controversy

Just recently, I became informed about TED, the nonprofit organization Technology-Entertainment-Design founded in 1984 to increase the spread of great ideas from the best and brightest thinkers in the world. You should take note of this company as well because each year they host a series of talks limited to 18 minutes, many of them videotaped, by just those people who matter most--the thinkers, the problem solvers, the entertainers, the communicators who inspire, who dare seek new knowledge and whose ideas change the future. Check it out.

I learned about TED because my interest in evolution and its product, the biodiversity around and within us, led me to seek a talk by E. O. Wilson, the famous myrmecologist from my home state of Alabama, who was unveiling his dream to form the Encyclopedia of Life (EOL; a talk you should watch when you visit TED's site). After watching his eloquent and creative discourse dreamcasting a vision for something so near and dear to my mind, its emotional and rational centers, I next clicked a hyperlink to hear Richard Dawkins' talk given, I believe, at the same conference.

In his talk, the Oxford professor nicknamed Darwin's rottweiler, outlined a course of action for atheist darwinists: come out of the closet with a purpose of vocally and militantly expressing a wake-up call to the world: Darwinian evolution by natural selection is hostile to religion, which is equivalent to a virus which infects the world by childhood indoctrination leading to anti-intellectualism, xenophobia, racism, sexism, terrorism, contempt for honest pursuit of truth, and the naievte of blind faith, and so on. As electrifying and discussion-sparking as this topic is and can be, what I found more incredible was the reasoning behind it. Dawkins points out in his talk how the religiously-fueled ignorance of our times has led to major misunderstandings and political and religious debate about evolution, the opposition calling themselves creationists, or proponents of "intelligent design." This debate has recently heated up to the point of being one of the most intriguing and hottest topics in philosophy, biology, and theology today. The reason I am writing this is that I agree with Dawkins on at least one point. This is war.

Like many others, I'm not sure whether I'm willing to commit to a position that says religion is useless, baseless, and that its bad weighs out its good in the function and roles of society, that Darwinism absolutely results in a rejection of all religious and spiritual belief. Richard Dawkins and Daniel Dennett represent prime examples of philosopher-scientists who radically support a materialistic view of science and the mind. On the other hand, I am more than sympathetic to and more than angry about the fact that a well-funded, conservative, anti-evolution coalition is trying to challenge evolution theory, to debate with science using political and pseudoscientific tactics, and to re-define for their own purposes the nature and regulation of the scientific enterprise, even of society.

I would like to think it necessary to burst on the scene, expose the liars and frauds, dish out powerful testimony against evil-doers I speak of, publish eloquent and popular books, and vanquish my foes--the foes of humanity, perhaps--once and for all, while gaining fame and fortune or at least a little respect that Rodney Dangerfield couldn't. I would like to be the first person to stand up and refute the "scientific" propositions of creationists, to discredit and disprove their stance to the point it be crushed under the weight of the truth. But I am not T. H. Huxley. I am not Michael Ruse. I am not Kenneth Miller. Sadly, brothers and sisters, it is not for me to do any of these, as far as I am aware. Why? Because they have already been done!

Over one hundred years ago, scientific debate about the validity--the fact--of organic evolution by natural selection was settled by scientists for the world. In parts of Europe and the United States, however, this argument has been resumed over the past few decades. Not for scientific reasons, either. Instead, a political, philosophical, and religious movement I have noted has supposedly brought this issue back into the arenas of public debate. Many, many minds have been engaged. I would like to point you to the truth, one that will lead no fair-minded and intelligent person astray. As I have studied philosophy and science and followed this debate for many years, this may take several posts. As a matter of fact and duty, it's worth taking years to follow this debate, maybe even (I hope not) my whole life, if need be. It is my opinion that everyone should become educated about this important debate because we cannot afford to lose what's at stake: scientific education, science-religion relationships, the way we think about the earth including the biological realms, the way we view our humanity, the way we view our work, et cetera.

As I consider how to present this, I must build upon the directions I started in. The fact is the cat's out of the bag. Intelligent Design (a dressed up for Sunday church version of creationism, or design theory) was taken on by Darwinian evolution, by modern science and philosophy and defeated long ago. This horse has been dead for years. So why still hit it? Hidden agendas. Money. Fame. Desire to impose one's own beliefs upon others. Public Relations. These sum up, in part, the motivations of the creationist Opposition. Since the intelligent design (ID) creationist movement is literally dead in the water already, I feel like it would be a good start for me to upload hyperlinks to information from both sides of the modern argument, so that you can click on these resources and learn about them yourself. So, your homework assignment, class, will be to read all this material, consider it thoroughly in your minds, then get back to me and tell me (a) which side you think is winning, (b) what you think science is, (c) how you define evolution vs. creationism/ID, (d) what the purview of modern science is vs. reasons for the debate, and (e) how you feel this impacts your view of yourself, your world, your beliefs about the world, and your desires for your life and that of others. Ok?

So, I'll set the stage by explaining a bit about the sides (providing links, citations), and then set you loose.

SO, the losing side is the ID side. The winning side is and must be that of biology and its central theorem, descent with modification through natural selection and other mechanisms. What we are on the verge of is the absolute loss of all theological and religious credibility, the complete abolishment of ID's "scientific legitimacy" (I believe this has already taken place), the ruin of several people's careers, the improvement of science education, more education for the masses, more scientific discoveries, and a growing hostility towards religion, which will continue to be degraded by modern science a little each day from this day forth. Ok? Like it or not, this is the truth about the world, or nearly so. But who are the major forces, who will the players be in the future? That's what I've been holding out on, enjoying your captivation for this whole time.

THE LOSERS

First, let us discuss the "losers." That would only be courteous. Creationists claim, in essence, that the world is too complex to be understood, so they envoke a supernatural force, a "designer" whose hand has been at work setting the unique wonders of the natural world in their respective places from before time began--namely, God or Allah or whatnot--as an explanation for what science "can never figure out." The argument goes, "At some point, the universe breaks down so that I cannot understand it. At that point, I decree by fiat that God is the only explanation for those things I cannot know." Put another way, the argument may sound like, "The biological world is so well put together, so irreducibly complex, that it gives the appearance of something intelligently designed, thus a designer must have been active in its origin." This teleological (circular) argument dates back to 1802, when William Paley published the argument from design in his book, Natural Theology. His argument was a watch's fine innerworkings implied a watchmaker, thus so too did the wonders of nature imply a designer, or God. This line of reasoning supported the widely held religious/scientific theory of special creation, which stated that the world was created by God (often, this was taken in reference to the Genesis account of creation in the christian Bible), with species being relatively fixed but adaptively plastic essences which did not change ultimately through time (this reference gives better historical background; though I cannot agree with it fully, it is a 127 year old perspective that should be considered by anyone weighing the evidence in this debate; other references include this fine evolutionary biology textbook, which discusses both sides; also look here; and see this link, where a scientist reviews a book by a theist in 1898, the year my great-grandfather was born).

When Darwin published his major work, On the Origin of Species... (1859), it provided a testable scientific explanation of facts (a theory) gathered from Darwin's readings and discussion about naturalistic phenomena, which was a powerful and influential proposition. The theory of evolution by natural selection, or Darwin's main argument in his book, was important first because it provided a mechanism explaining biological diversity, but second because it infinitely crippled the theory of special creation and the argument from design. No longer could supernatural arguments be used to argue about natural phenomena. Design arguments were trumped in the sense that Darwin's theory showed that incredible complexity could arise by gradual change of form, without envoking a designer or vital force. Not only did this argument win on its face, but this was a more parsimonious explanation (click the link for Occam's Razor). These facts known in 1859, as well as many others gathered and published in scientific and philosophical journals up to the present day, close the coffin on the Opposition.

In the 20th Century, a right-wing religious group began pointing fingers at evolutionary theory as the root of many different sins and evils found everywhere in society, especially as this theory became associated--even synonymous with--atheism. These activists claimed that homosexuality, sexual immorality, atheism, disease, and many other problems had their origin in evolutionary thought influences upon culture. Since the 1800s, religion has lost converts because evolution does, in fact, often lead to atheism. In the 1970s, a movement based in conservative Presbyterianist congregations that has now continued to encompass christians of many different denominations began developing a movement which crystallized in the late 1980s and early 1990s in the current creation-evolution debate. This movement is called Christian Reconstructionism (also read here, here, and here). Luckily, it is headed toward its demise.

Christian Reconstructionism (ChR) is something all the losers, including you if you place your rational faith and belief in intelligent design/creationism, support because it is a major political force funding and negotiating the creationist movement, particularly in America. Ultimately, conscious or not, by supporting ID, people are supporting this movement. Christian Reconstructionists believe (a) the word of god in the Bible is inerrant (but fails to prove this; in fact, many young christians today struggle with doubts over the contradictions in the Bible, especially when looking at the Old and New Testaments side by side), (b) christianity is the only correct religion, (c) Old Testament moral law applies to all people and all nations except those laws which other parts of the Bible later came to replace (which really means contradict, if we speak literally), (d) that Calvinism is required to obtain eternal life and effect social changes of the movement, (e) Christ will return after the whole world is evangelized or nearly so, (f) atheistic society will self-destruct and leads to moral decay a prioi, and (g) that ChR will result in suppression of all other world religions and reversion to Old Testament law including stoning of adulterers and homosexuals, no body piercing, no tattoos, etc, and that the world will be evangelized and Christ will return after they peacefully alter political and legal conditions to reconform to Old Testament Hebrew scriptural states. This is the most ridiculous thing I or any other thoughtful human being have ever heard of!! Is it not? A major problem is that these views are weakly aligned with much christian teaching and practice, but they represent a going-by-the-wayside extreme fundamentalist minority, which has been discredited.

Now, whether you are an IDer or a Darwinist, do you want those kinds of people in control of society and the fate of the world in accordance with their beliefs? How, Christian, will the Hindu, the Buddhist, the atheist, the Thor worshipper, the Wiccan, your neighbors and friends respond to this movement? How are they responding? Well, given the current failure of religious-led/supported government, probably not so favorably. And with good reason. Not only is this cause completely militant and purposeful in its attempt to find dominion over the earth for the Lord, but also they have been carrying out their plans secretly, immorally, and unscientifically.

In case you didn't know, rotten is the new slang for morally or logically wrong or unacceptable (also look here). I think this is a fitting description for the Discovery Institute (see their website, Discovery Institute Intelligent Design Campaigns and Wikipedia description of DI), the major "think tank" of the ID/Christian Reconstructionist movement. Dr. Michael Behe, a biochemist at Lehigh University in New England, is the "posterboy" of this group, one of the few valid scientists in the ID ranks. He and other famous scientists and philosophers, most notably William Dembski represent key spokesmen for the ID side. To give you an example of how unethical this group is, just check out the website above. Notice anything fishy? (1) A group of mostly religious scientists, writers, and politicians describe throughout the website ludicrous responses to real science and the "winners" despite major losses, (2) they present pseudoscience, and (3) the images, production, and website name on this website and related materials give the false impression of a reliable source of scientific information (Look here for debunking article about the website banner. Why would DI give away their rottenness with their banner? Slight of hand. They want you to believe they represent scientific and faith authority.). In disguise, the DI slams evolutionary theory, science, and society. You and I had better watch who's talking and watch who's podcasting and watch which resources our sources cite and get their data from. Does it reference the DI? If so, beware of this group and the innane plot I have described.

"So, what?" is a common question among the learned and skeptical. I ask it about nearly everything I hear or read. It is my duty as a biologist to always it about science. So, what if you don't believe me when I say this is true? All around the world there is evidence of biological processes pointing to facts about evolution (you can interpret this as evidence about God's direction of the world, but this is non-science). Readily available by mail, books, articles, magazines, and the internet are credible resources that back up every claim I am making. Books and articles by real, even religious scientists like Dr. Kenneth Miller expose the major flaws, failure, and immorality of the ID/ChR movement (both are wrong, whether people take one or both sides). Thousands of peer-reviewed books and articles in scientific journals testify against creationism. Even religious people, like myself, have turned from creationism to accept the truth of evolution as fact. Hesitant to believe the plot I've outlined? Then you'll be even happier to know that the IDers years ago formulated a plan for their take-control of American science education, the extinction of evolution and so on. It is called the Wedge Document and was leaked within the last decade just before key court cases pronounced ID as "unscientific" and thus completely without scientific basis, conferring upon it NO PLACE in the science classroom. Here is a copy of the Wedge Document. Here is another, also from a creationist. You can read it for yourself.

From the language of the Wedge strategy, which prominent political scientists, biologists, and educators such as Dr. Barbara Forrest have exposed and criticized, the ChR/ID movement makes several claims to support their social, religious revolution. They make it abundantly what their position entails (though there's much they are holding back, like the rest of radical Christian Reconstructionism). The Wedge starts off with their central theorem: man was made by God in the image of God and this is the foundation of Western civilization. This has its origins in Genesis (for the christian, so far, so good). Then, they move on to describe their opponents. Their claims are that the fight began when the rise of modern science brought with it a materialism in direct contradiction to what thier own beliefs held (theism, dominionism, man as God's image, etc.). This materialism, says the Opposition, gave rise to moral decay, philosophies which were not so egocentric or anthropocentric, and utopianism. The Wedge, brought down from Mount Siani by Dr. Phillip Johnson and friends, goes on to say,

"Discovery Institute's Center for the Renewal of Science and Culture seeks nothing less than the overthrow of materialism and its cultural legacies. Bringing together leading scholars from the natural sciences and those from the humanities and social sciences, the Center explores how new developments in biology, physics and cognitive science raise serious doubts about scientific materialism and have re-opened the case for a broadly theistic understanding of nature. The Center awards fellowships for original research, holds conferences, and briefs policymakers about the opportunities for life after materialism." (emphasis added)

In the sames spirit Ken Miller has written in concerning Michael Behe's new book, which he reviewed in a piece published in Nature, the Wedge makes "a nice argument, except for the annoying fact that it is wrong." And it is wrong on many counts. A major conclusion of Christian Reconstructionists supported by other creationists is that evolutionary theory brooded materialism. This is a fact. But this fact requires some explanation, because materialism is not very well understood by laymen as a result of multiple use. On the one hand, materialism refers to preoccupation with material things and desires overruling the spiritual in the lives of humans; on the other, materialism is a view of the world contending the world and universe, a priori or operationally, are made of matter or material objects and not supernatural ones. The Wedge and ChR/ID revolution is really worried about both of these, but targets the second because of its place in the philosophy of modern science. To clarify, we are talking about the second kind of materialism here!

Scientists follow either ontological naturalism or materialism (ON, OM) or methodological naturalism or materialism (MN, MM), or some variation of this theme. MN says that there is no supernatural entity or vital force considered in scientific work because science is about testable or falsifiable predictions and explanations based on materialism and supernatural things or theories do not fit this definition, thus are non-scientific. ON goes one step further and says there is no supernatural thing anyway, so why bother acknowledging it in this way. Militant atheism is joined to ontological naturalism and radical materialism, as that supported by Dennett and Dawkins and, to a lesser degree of acknowledgement, Frederick Crews and many others.

So, we see that science can be seen as more of an occupation, but many times is an integral part of someone's world view or ideology, if not comprising most of their set of normative ideas. The ideology of science has been called scientism. I am learning about this now. It seems closely allied with the calls from creationist camps about the deification of Charles Darwin and the faith of scientists in their "religion" of materialism. I confess I don't know much about it and want to know more. The point is that whether you see science as a category, a concept, an ideology, or what, supernatural phenomena are not scientific in the strong or weak sense of the word. These distinctions hold the not-so-secret key to other reasons why the ChR/ID movement fails.

For one thing, they contribute to exposing the Opposition as a movement which lacks integrity. But I'm not sure how important this is, because these kinds of attacks seem inconsequential in the scheme of things, aside from potentially persuading those mindless people who fail to critically consider the situation themselves. Second, the ChR/ID argument goes A = creationism, B = evolution (materialism);

1. A vs. B
2. B is wrong
C. Therefore, A

This argument rests on the logical fallacy that calls premise 1 especially into doubt. It cannot be as simple as materialism is wrong, therefore the christian reconstructionism/ID is right. In fact, it is likely that the first premise could be infinitely extended to include... or C, or D... to infinite.

Many other Oppostion claims have been met with serious issue, called into question, and defeated in scientific journals, public debates, and courtroom decisions. Sift through these in the materials I provide below. The evidence is overwhelmingly in support of science as science, not the pseudoscience presented by the ChR/ID Opposition.

THE WINNERS

Up next? A description of the "winners" and several of their recent victories against this selfish, unethical, religious minority trying to hijack our science education and indoctrinate a world of brainless, anti-science, anti-evolution, anti-intellectual christians. For now, I'm going to bed and you can follow the links below to interesting content on these matters. I strongly encourage comments. Which side of the war do you want to be on? The winning side or the losing side? I know it's cliche, but the truth will set you free. And if all goes right it will prevail. We cannot afford the opposite. Please look for my next installment about this issue. Also, I encourage everyone to respond with your thoughtful comments after reading through the materials I have presented.

Articles and Talks against ID, DI, and creationism:

Ken Miller Talk in Ohio, 2006? - YouTube
http://youtube.com/watch?v=JVRsWAjvQSg


Barbara Forrest's Position Paper on the truth about the ID movement
http://www.centerforinquiry.net/uploads/attachments/Forrest_Paper.pdf

Skeptical responses to DI "scientific" podcasts



Populist Party in America calls for concern about DI

Americans United for the Separation of Church and State

DI: harming us with pseudoscience article

Famous articles on the ethics of belief (here, here)

Scientific papers of major players in the ID-evolution debate:

http://www.bioone.org/archive/0006-3568/55/3/pdf/i0006-3568-55-3-280.pdf

http://www.bioone.org/archive/0014-3820/56/8/pdf/i0014-3820-56-8-1721.pdf

http://www.bioone.org/archive/0002-7685/65/9/pdf/i0002-7685-65-9-646.pdf

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1467-9744.2005.00746.x

http://www.asa3.org/ASA/PSCF/2003/PSCF3-03Collins.pdf

Ken Miller's review of Behe's new book http://www.nature.com/nature/journal/v447/n7148/full/4471055a.html

Famous scientist Jerry Coyne shatters Behe's new book! Also, he illustrates how Behe's own university doesn't support him, especially since he really botched things with his latest edition, Edge of Evolution http://www.powells.com/review/2007_06_14

http://www.ingentaconnect.com/content/bpl/moth/2002/00000018/00000002/art00004

Annual Review of Genomics http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.genom.4.070802.110400?prevSearch=fulltextfield%3A(%22intelligent+design%22)

Famous evolutionary biologist Futuyma debunks Darwin's Black Box http://bostonreview.net/BR22.1/futuyma.html

Another Forrest Paper http://www.infidels.org/library/modern/barbara_forrest/wedge.html#_edn1

Defending Science Education http://www.jci.org/cgi/content/abstract/116/5/1134

Modern Philosophy of Mind http://watarts.uwaterloo.ca/~celiasmi/Papers/lyons.html

Science of the Soul?http://www.naplesnews.com/news/2007/jul/12/science_soul/?neapolitan

"Irreducible Complexity" goes down hard again!http://www.ccrnp.ncifcrf.gov/~toms/paper/ev/behe/

Reference on the Argument from Design http://www.infidels.org/library/modern/theism/design.html

"More Crank Science" article http://bostonreview.net/BR22.1/coyne.html

"New" argument, same old objections http://www.journals.cambridge.org/action/displayAbstract?fromPage=online&aid=26583


DI, ID websites:

DI response VII to Kitzmiller


DI homepage, "evolution news and views" (yeah right, from a twisted bunch of radically conservative, pro church/state merger, pseudoscientific, uneducated bastard liars)



Jack Russell Terriers & Cockroaches article (please respond)

Phillip Johnson on THE WEDGE
http://www.touchstonemag.com/docs/issues/12.4docs/12-4pg18.html

"Creationism Research" = oxymoron
http://www.creationresearch.org/creation_matters/pdf/2002/cm07%2004c.pdf

Christian Reconstruction site/book
http://forerunner.com/forerunner/X0505_Parsons_-_What_is_Re.html

Behe's response to critics
http://www.springerlink.com/content/g527h45501l632v8/

Another Behe botch up
http://www.arn.org/docs/behe/mb_brresp.htm

Debating Design Book - both sides presented equally and rationally
http://www3.cambridge.org/uk/catalogue/catalogue.asp?isbn=9780521829496

Absolute Baloney websites illustrate creationist anti-science/design argument:
http://evolution-facts.org/nature1.htm

Get a life, Dakota Voice, you are a fool!
http://www.dakotavoice.com/200706/R/20070619_BE.html

Jim Schicatano gets it all wrong
http://home.att.net/~jamspsu84/ttocmain.html

Richard Dawkins







So, recently I've been researching the speeches, science, writings, and life of the famous Richard Dawkins. Dawkins is one of the most confrontational, radical, outspoken, and talented scientists of the past century. It is no great surprise, therefore, how he represents one of the most famous of all communicators, scientists, and atheists in the history of the world! His latest book, The God Delusion, has sparked controversial reviews and heated reactions from many people around the world. Again, no surprise this is a best-seller. I am interested in talking about Dawkins, his books, his life, and in particular the range of opinions about his latest book and exploits, if anyone else is willing to engage. Here are some links to information about his life for the uninitiated. For the learned near my town, let's start a book club. ~ JB
Links:






Wednesday, July 11, 2007

I was NOT "underwhelmed" by Live Earth, were you?


On Monday, July 9, the Environmental News Network ran a story examining the global concert event for climate change awareness--Live Earth--led by former Vice-President Al Gore, which took place this past weekend.


Their review was less than stellar, claiming that Live Earth "rocked the world" but did nothing to change it. What did they intend to leave us thinking or feeling after scrutinizing the overall low intensity news response, the choice of Madonna as a participant, and the difficulty of mixing music with real problems and important causes in the world? Basically, nothing, except the cheerful news they thought Live Earth was a dismal failure but Germans were happy with Snoop Dogg. That ain't much to offer.


So, I don't know if anybody reads what I write, but like everyone else blogging, I'll be squeezing off my two cents worth.


First and foremost, Live Earth was awesome. It was awesome to see some action, to see steps taken to highlight a real problem and seek support for a solution. A Darwinian view of life is a rational and humanistic view, a view which prizes philosophical morality and is sensitive to moral philosophies about how we live our lives with respect to the biosphere. This means that moral (understood to also be educated) Darwinians support the logical and personal decision to be conscientious and supportive of environmental issues like climate change. For a serious scientist who reads and teaches about conservation, and one who recycles excess paper and comingled recycles every day and is mindful of his carbon footprint, seeing somebody get out there and raise awareness about this problem and do something about it, not just talk about it, was a rare and beautiful event.


The second reason I view Live Earth as a success is that it brought a relevant message in a relevant format. That speaks success to me. Young people showed up, in case you didn't notice. The celebrity status of the performers was a good thing, an eye-catching and inviting piece of the puzzle, not something that reduced the credibility of Live Earth. Criticizing the concert series only underscores a critics unique position to bad mouth. It's an easy out. The environmental philosophy (or lack thereof) of the performers has absolutely no impact on the credibility of the message of LE. The truth is that Live Earth was relevant. I am proof of that.


I was able to watch Live Earth via the internet. Including myself, approximately 2 billion people are thought to have witnessed the event. I sang along with Bon Jovi and Jack Johnson, and that's not all. Ultimately, I felt a deep connection with hundreds of thousands of strangers who (a) enjoy good music and (b) showed up for an event that supported an arm of the environmental movement. Undoubtedly, even more have heard about the event orally or by way of other forms of advertisement than was reported. Wasn't your passion ignited as well? Weren't you moved by the show of support? If so, your duty is action. Based on the reviews, if you thought Live Earth was productive, you need to stand up and say so. If not, like the ENN folks, then I would be willing to accept skepticism, but barring it from the logic, I would only be willing to call into suspicion the integrity of your environmentalism. And that's ok. You're just immoral or illogical, a fool either way.

Tuesday, July 10, 2007

The Cell Cycle

Multicellular eukaryotes that reproduce via sexual reproduction present a case we are all familiar with. During or after sexual contact, gametes fuse to form a zygote, a single cell containing hereditary material from each parent. This description represents only a small snapshot of eukaryotic life, with a couple frames following fertilization thrown in for free. We may reason about this relatively singular event series and its importance, but we cannot help noticing more than the most basic case, two separate entities gave rise to one new entity, just happened. In particular, we know that the individual gametes must have had different qualities and different origins, and furthermore the zygote goes on to become orders of magnitude larger and more complex. In this post, I will briefly summarize the roles of cellular division in gamete development and human physiology and review the cell cycle and its regulation. I then will conclude with some comments about evolution as it relates to this topic.

Despite the lopsidedness of the introductory example, cell division is integral to the evolution and life of single-celled and multicellular life. The purpose of cell division in single-celled organisms is to duplicate the whole individual! In complex multicellular life forms, such as Homo sapiens, serial cellular divisions and differentiation give rise to extraordinary physiology from single-celled starting material. Also in humans, cell division occurs to regenerate certain tissues hence organs that degrade through time. Among these are our red blood cells, skin, hair, and certain glands. Many interesting factoids have been quipped about estimates of turnover during this process and other interesting phenomena. Check a couple out
here and here. Most of my discussion will focus on eukaryotic cells and attempt to avoid these.

Dividing cells spend their time in one of two states, (1) Interphase (growth and duplication) and (2) mitosis (splitting into two new cells). These two processes can be broken down into a series of smaller phases. Overall, the cell cycle, or cell division cycle or however it may be called, always involves the following phases in sequential order under normal conditions: G1 phase, S phase, G2 phase, and mitosis. Here, G stands for "gap" so that G1 means "gap" 1, S stands for "synthesis," and G2 refers to "gap" 2. Beyond these, mitosis is traditionally split into several phases, itself. These, also in sequence, are termed (a) prophase, (b) prometaphase, (c) metaphase, (d) anaphase, and (e) telophase + cytokinesis. New cells formed during mitosis are called daughter cells. This early institution of organization may be helpful. On the contrary, you may be asking what I first asked when I heard these terms for the first time, "What does all this mean?" Discussing the cell ultrastructure involved often helps alleviate this pain. This will be touched on after describing the cell cycle.

While there are distinct phases of the cell cycle, all three non-mitotic phases are similar; in each, the cell grows as it duplicates chemicals, organelles and proteins. The S phase is unique, because it is the phase where DNA is duplicated. Interestingly, the S phase is considered the longest phase of the cell cycle, filling about half the total amount of time necessary for average human cell division (Campbell and Reece 2005).

Cell Cycle Regulation (van den Heuvel 2005; Campbell and Reece 2005; others)

The cell cycle is controlled by several different types of membrane-bound enzymes and other factors conserved (i.e., found) in most dividing animal cells. Studies indicate major importance of three or four different kinds of kinases and other genes in this mosaic of regulatory pathways. Also, the cell cycle may be controlled by extrinsic or intrinsic factors. Generally, external signals only regulate whether or not animal cells reproduce up to a point called the restriction point or G1 checkpoint. On the other hand, a number of important internal factors regulate the cell cycle intrinsically from this point.

The main paradigm of cell cycle control is one of activation-inactivation cycles generated by changes in the amounts of regulatory factors, cyclins and kinases. Kinases "activate" or "inactivate" different proteins controlling cell division by substrate-level phosphorylation at checkpoints such as the restriction point. Kinases themselves may also exist in active or inactive states corresponding to their position with respect to cyclins. Activated and inactivated kinases are attached or unattached to cyclins, respectively. This is why these kinases are called cyclin-dependent kinases, CDKs. As cyclins increase and decrease in thier relative concentrations in the cell (and CDKs remain relatively constantly concentrated), CDK activity changes disproportionately, with activity increasing abruptly after gap 2 then falling as cyclin is degraded during mitosis. Actually, synthesis of cyclins occurs from S phase through gap 2 phase. While cyclins are degraded, CDKs are thought to be recycled during this process. So, why is this a regulatory pathway anyway? Because without cyclin accumulation, mitosis is not signaled. An important CDK complex called "M-phase promoting factor" signals spindle formation, nuclear envelope breakdown, and chromosome condensing. Without these, M phase, thus the cell cycle, would never be completed.

Mitosis

As I mentioned in an earlier post, DNA (of eukaryotes) is housed within the nuclei in the form of a substance called chromatin, in which histone proteins and tangled nucleotide strands are incorporated together. This chromatin is loosely distributed in long thin fibers. During S phase all the genetic material replicates itself, but chromatin is still in loose form. Later, during mitosis, the chromosomes condense and the cell actually divides. A unique set of machinery is involved in these processes. Most notably, cytoskeletal structures provide substrates (analogous to small roads or steady surfaces in the cell) for chromosomes to be transported along by motor proteins; also, centromeres play a pivotal role. Perhaps the best way to describe mitosis is the common way, or detailing the events at each phase of the process.

Prophase: The prefix pro- means this stage is "before, or preceding" the following other phases of mitosis. During prophase, chromatin is condensed into recognizable chromosomes. Originally, these were single units. After duplication and condensation they represent a pair, each called sister chromatids of the other. At the center of these chromatids is a region known as the centromere, which connects the chromatids, or copies of the original DNA molecule. Tan cuidado! The centrosome-centromere problem may confuse you. At the same time these chromatids assemble, the centrosomes begin sending out microtubules, which push the centrosomes farther apart by physical force.

Prometaphase: Here, the prefix meta- means "growth" or "unification, or important" phase, so this phase precedes the really unifying step. Prometaphase includes breakdown of the nuclear envelope (microfilaments and pore complexes), which degrade substantially to clear space for metaphase and anaphase. Also, the staging of the microtubules becomes much more complex, extending across the cell to connect with special structures formed at the centromeres, called kinetochores. Kinetochores are specialized proteins. There is a name for microtubules which are now very obvious in the cell--they're called spindles. Some spindles connect with kinteochores, others connect with other spindles across the cell.

Metaphase: Metaphase is one of the most time consuming and important phases of mitosis. During this time, chromosomes are aligned on a plane bisecting the distance between the centrosomes, which is termed the metaphase plate. It's not a real plate or plane, but rather an imaginary one. Microtubule spindles attach at kinetochores closest to them such that chromosomes line up with kinetochores facing each pole of the cell signified by centrosome position.

Anaphase: Ana- means "true" or "original." However true or original this step is, a fact is that it's the shortest phase of normal mitosis. It is during anaphase that the chromatids are ripped apart from one another by the microtubules, thus taken to their respective poles of the cell. For some reason--ah, because the end products are called daughter cells--the chromatids become called daughter chromosomes after this point. Remeber the spindles that hooked up with one another, not the kinetochores? At this point, those push off one another to help distance the chromosomes and increase the distance between the poles of the cell.

Telophase + Cytokinesis: Finally, telophase unites the genetic material of each daughter cell into an enclosed nucleus while cytokinesis splits the cytoplasm via invagination of the plasma membrane (involving microfilaments) and segregation of the fluid matrix making up the innermost cellular space. And mitosis is over, just like that. You can remember the order of these phases by memorizing the names, memorizing the prefix meanings, and or memorizing the order like this P2MAT.

Cell division from the standpoint of evolution and disease

According to Campbell and Reece (2005), "As eukaryotes evolved, along with their larger genomes and nuclear envelopes, the ancestral process of binary fission [bacterial division] somehow gave rise to mitosis." Researchers have actively been seeking answers to persistent questions about the mechanisms involved in mitosis. This work has included plants, many of which reproduce asexually through mitotic cell-lineages (Fagerstrom et al. 1998), as well as diatoms and bacteria.

Save the best for last. That ability is one of the greatest given to the human condition, and exactly what I think I've done waiting to talk about the coolest parts of the cell cycle, apoptosis and disease! Trust me on this one.

Scientists' understanding of CDKs' functions in cell cycle regulation and their interactions with other chemicals are just beginning to be explored. We have discussed what we know about what happens when things go right in cell cycling, but what about what we know about what happens when things go awry? For me, this was one of the most interesting and exciting facets of my introductory cell biology class. I hope your decision about which part of the cell cycle and its regulation, like mine, hinges upon the next few pieces of information.

If S phase replication goes wrong and DNA is damaged, this can have negative effects. So, cells halt the cell cycle by slipping into "gap zero" phase, or G0, while damaged components are repaired. Also, it is integral that mitotic spindle fibers attached to kinetochores, and the right ones at that. So, cells can halt motion to the next phase of the cycle in the even this happens. HOWEVER, if things don't get fixed or something else dysfunctions at these crucial times, the cell may induce suicide, or apoptosis (a.k.a., "programmed cell death").

An important gene regulating both of these processes is p53. p53 is in a special group of tumor suppressor genes, which keep the cell from slipping into cancerous states. Of course, I haven't talked about cancer. So, what I mean is that if things go awry (e.g., if DNA is damaged by an environmental factor instigated by a physical action, such as smoking), the cell may never be able to turn off (step into gap zero states or die via apoptosis), thus it may continue dividing infinitely with misreplicated genetic information. Cells in this state cause cancer by creating many clones of themselves (a tumor), which are harmful to the body because they fail to recognize tissue boundaries and may travel to other areas of the body, depleting normal tissues. p53 blocks the cell cycle by inactivating CDKs and has the power to induce programmed cell death in abnormal cells. WHEN p53 is doubly recessive (mutant), these functions are not carried out and cancer will develop beginning, perhaps, with a single damaged cell.

A report on wikipedia.com resounds a common statistic, that cancer is responsible for approximately 10-20% (13%) of all human deaths. In this way, we see that the cell cycle is not only important to our growth and complexity, but also that factors along the way play a critical role influencing our health and well-being. Similarly, mistakes during mitosis result in genetic variation among individual offspring of parents, ensuring natural selection has lots of material to work with in healthy populations. Now that you know so much about a process that led to your diversity and uniqueness, watch this time-lapse video of cell division!

References:

van den Heuvel, S. Cell-cycle regulation (September 21, 2005), WormBook, ed. The C. elegans Research Community, WormBook,
doi/10.1895/wormbook.1.28.1, http://www.wormbook.org.