Genetic Machinery of Natural Selection

From Mbscientific_wiki

Gene Structures, Proteins and the Shape of Life

The figure below demonstrates DNA structure (or batter yet play with the structure in this interactive model: http://www.johnkyrk.com/DNAanatomy.html )

DNA consists of coding parts (exons) and non-coding parts (introns). One of the jobs of DNA is to make proteins that do all of the cell's functional work, including determining what a cell will be. To put things in context, shapes form as cells divide and differentiate. The fertilized egg (zygote) divides into a bunch of undifferentiated cells in a uniform clump called blastula. During gastrulation, when cell differentiation occurs, three major cell lineages are established. They are the Ectoderm (shown in the diagram in blue), Mesoderm (red) and Endoderm (yellow). Following gastrulation, various cell lineages are derived from these three primary cell types. For example, the Ectoderm gives rise to the epidermis and its derivatives such as nails, hair and teeth. The cascade looks like (source: http://www.luc.edu/depts/biology/dev/devm.htm):

Morph Animation: See a comparative embryonic developmental morphology of baby human, pig, chicken, and fish at PBS:NOVA - Odyssey of Life

At each step a number of genes are deactivated and a number of genes activated (see a movie of gene activation/suppression). The expressions (i.e. the work) of the activated genes determine what proteins are created and therefore what the cell will be. The chart below establishes a typical number of proteins in the cells of several different species (source: www.nature.com, article on human genome project):

Transcription, Splicing, Translation and Protein Generation

DNA doesn't produce the proteins directly. Rather, DNA is Transcribed to messenger RNA (mRNA) in the Transcription Process (See the movie). Next the Splicing Process strips out the introns, leaving only the functional exons (See the movie). It is the spliced mRNA that codes the proteins in the Translation Process (See the movie).

Given that relationship, we can potentially tell what segments of the DNA, i.e. genes, are responsible for the manufacturing of what proteins. And, given the functionality of a given protein, we can deduce what gene is responsible for what functionality. Relationship between codons (3 letter slice of DNA) and the amino-acids (protein units) they code for is given below:

Legend: Amino acids specified by each codon sequence on mRNA. Key for the above table:

Ala: Alanine	Cys: Cysteine	Asp: Aspartic acid	Glu: Glutamic acid
Phe: Phenylalanine	Gly: Glycine	His: Histidine	Ile: Isoleucine
Lys: Lysine	Leu: Leucine	Met: Methionine	Asn: Asparagine
Pro: Proline	Gln: Glutamine	Arg: Arginine	Ser: Serine
Thr: Threonine	Val: Valine	Trp: Tryptophane	Tyr: Tyrosisne

A = adenine G = guanine C = cytosine T = thymine U = uracil

In the ribosome mRNA codons produce the aminoacids which are then chained together to make the functional proteins. In the last chapter, we defined 6 major cell functions (structural, replicative, metabolic, motor/sensory, signaling, defense/immunity) and eluded to biotic aggregates that manifest these major functions (a more complete list of functions are spelled out in the cell protein chart above). Now we know what these functional aggregates are: DNA-mRNA-tRNA-Proteins. In this movie you will see an example of the functional aggregates in lactose absorption process in a cell (an example of food intake process): http://www.youtube.com/watch?v=oBwtxdI1zvk.

Cell Division, Differentiation and the Shaping of an Organism

An organisms takes shape as the embryo divides and differentiates. (See a movie of DNA replication). During differentiation, the activated genes and the proteins they produce give rise to the identity and the functionality of the cells. The genetic network that successively activates and deactivates various genes as the cells divide is the mechanism of cellular differentiation, as the cascade below demonstrates:

In this animation we can see a baby Sea Urchin forming through the cell division-differentiation process http://www.stanford.edu/group/Urchin/urchin.html.

So you can look at DNA as a series of time-lapsed functional and regulatory networks. The functional parts make functional proteins and the regulatory parts make regulatory proteins that become hierarchically activated at various stages of cellular differentiation (body formation). I'm going to include a gene network model for endoderm-mesoderm differentiation (without explaining it, otherwise we'll be here for a month- source: http://www.its.caltech.edu/~mirsky/endomes.htm):

Presently the sequences of the genomes of humans, mice, various bacteria and viruses have been completed. Further DNA sequencing work is continuing on a variety of species under study. In a nutshell, we are approaching an era where we can study biotic morphogenesis from an elemental, genetic angle. For example if we suspect that two species are related, because of morphological and behavioral similarities (e.g. man and chimpanzee), we can compare their genetic sequences (man and chimp have ~%99 common genes) or the protein sequences that genes produce and arrive at a quantitative measure to express their similarities.

Natural Selection, Genetic Evolution and Epigenetics

The genetic code tends to stay stable through replication. The exception is of course in case of mutations where spelling errors might creep in the process. Genetic accretion, i.e. pathways for adding new gene code to the network, e.g. via retroviruses, etc. is another way the gene code could get modified.

Then there is the environmental effects on genetic networks and that is the subject of Epigenetics (See a long movie on epigenetics from PBS/Nova). It turns out that:

a) the cellular intake from the environment has a direct impact on the genetic network, i.e. if, when and how the genes are expressed, and

b) if the environmental integration is stable (e.g. a lifelong diet), then the epigenetic effect might be stable as well. In that case the genetic network is altered to the point that the effect becomes hereditary.

I'll give an over-simplified example to drive home the power of epigenetics. Suppose there is gene that codes for capture and storage of fat (lipids) in the cell, for simplicity lets call that the FAT gene. Also lets assume that there is a suppression protein complex, lets call that SUPFAT, that suppresses the FAT gene. Now the ingredients of SUPFAT must come from the environment through cell intake. Suppose one of the ingredients of SUPFAT, lets call that SKINNY, is diminished. So on replication the FAT genes tend to get expressed (less SKINNY, less SUPFAT, more FAT genes ready to code for fat intake) and the cells tend to become fat cells. So that would be the resultant effect of the environmental factor on the functional genetic network, and the individual becomes obese.

Now lets take this thought experiment to the regulatory side of the genetic network. Lets say in the regulatory network there is a gene that codes for SUPFAT, lets call that FATKILL. Again, for the sake of simplicity lets assume that existence of fat inhibits a protein complex that expresses FATKILL. So on replication, FATKILL is not expressed, therefore the overall genetic network codes for fat. In this vicious cycle of a thought experiment, the obesity condition becomes hereditary.

Again, this thought experiment is way oversimplified, but it drives home the power of the environment expressed through epigenetics. And the point is that the genetic network is not an automaton in isolation, rather it is a part of the environment.

So natural variation of the genetic network might occur through mutation, accretion, and environmental effects on epigenetics. And through parental imprinting the variations will get amplified.

This would be a good point to try to answer the primal question: is biotic morphogenesis driven by design or is it accidental? Part of the problem is the way the question is posed as an either-or. Let's set the context and maybe that'll help. There maybe valid states that things can evolve to. But the valid state doesn't force the evolutionary process. Rather, it seems, the evolutionary process starts with the initial valid state and tinkers with it. Through the generations this tinkering happens over and over. It isn't accidental. It is driven by the bimolecular machinery, but it radiates in all kinds of directions and not necessarily only towards the valid state. With luck one of the directions of radiation actually points toward the valid state. The main problem with the valid state is that you don't know what it is before hand. Rather, it is something that emerges as the result of the evolutionary process. Take the emergence of animals out of water and onto land. Now we know that the bipedal morphology is a valid design. But the question asks whether the original fish design drove towards the bipedal state by some design or did it accidentally get there. The answer is both. We know lobed-fin fish probably evolved from ray finned fish. The lobes at the base of the fins provided the muscles that stand out from the flimsy fin bases of ray finned fish. And, when we look at the swimming motion of the living fossil, the coelacanth, we see a bipedal type of motion. But, the coelacanth is a creature of deep oceans. It doesn't come anywhere near land. The next cascades of evolution moved the lobed fish valid state in all manners of directions. One was the direction where the fin bone structure gets thicker and sturdier. That adaptation was useful for the fish that inhabited swamps. It allowed them to maneuver in between the trees and roots and avoid their predators. So they established that niche. The next evolutionary step would be conversion of fish air sacs to lungs, as in the lungfish. The creatures that combined these two traits happened to have the right tools to move about on land. The ones who managed to survive struck their niche on the shores. So the first amphibians were established. But they didn't just establish by themselves. The entire shoreline eco-system had to emerge along with the amphibians, otherwise there would have been no place for them to establish a niche in. So the evolutionary process has to involve the whole system. And only in the context of the whole system you can tell a valid state, and you know it because it has already been established. You wouldn't know it before hand. This is a perfect example of emergence of valid states from chaotic morphological flows, as has been evident throughout this exercise. (Note: See pictures and movies of tetrapod fish, living and fossil, in the section: Cells to Reptiles ).

Let's look at the tree of life from a lineage standpoint. You'll get a more detailed tree made up of actual individuals that make up the physical nodes that make up the tree of life (w=female, m=male).

One can see that a beneficial genetic mutation would potentially get inherited by the successive generations and establish a noticeable morphological change. But there's more to the picture though. You can also construct an upside down tree, consisting of all the different individuals through one's lineage that could contribute to its genetic makeup:

So one's genetic make up can consist of a wide variety of contributing sources. Now if you consider a whole population at any given time, by the virtue of this variety, you are going to see variations in the morphology of the population. That's where the natural selection model meets the genetic model. Of this given variety, one may possess a distinct advantage over the others. In the figure below, I combined the above two figures. Now assume that a helpful morphological mutation occurred in the yellow individual that propagated to their offspring:

Within the overall group the yellow individuals will have the advantage, therefore will have more offspring. Now suppose a calamity happens and only the yellow individuals, by the virtue of their advantage, survive. The end result will be a population that will be yellow as a rule and other variations would be the exceptions. So you need both genetically driven morphological radiation and natural selection to render the different morphologies that we see today as the result of millions of years of genetic morphological tinkering, interspecies relations and environmental conditions. Genetic, molecular, evolution would be the impetus of the morphological flow, and the environment (including all of the interacting species), would be the gatekeeper. The gatekeeper would hinder the unstable, inefficient designs and the stable, efficient ones would perpetuate. And that links up with the last section, evolutionary creation is both directed and accidental. The drive is the molecular evolutionary machinery, and the question mark is the larger environment as the whole. Think of the dinosaurs, they were doing just great for millions of years, then wham, an asteroid decided to park itself right on top of them (which is a good thing, for us, because that's how we had a chance to get here!).

Chapter Key

Chapter Key:

Morphological Flows, entities going through functional constructs thereby creating more complex entities with more complex functionalities:

DNA-(t+m)RNA-Protein functional aggregates == accretion mechanisms (Electro-Magnetism) ==> coalesced DNA-(t+m)RNA-Protein functional groups

DNA-(t+m)RNA-Protein functional aggregates == mutation mechanisms (various) ==> mutated DNA-(t+m)RNA-Protein functional groups

DNA-(t+m)RNA-Protein functional groups + supporting material in the environment ==constructor (accretion?) ==> Functioning Cell

functioning cell == replication and differentiation ==> functioning cell clusters and groups (organs)

functioning cell clusters and groups (organs) == cell-cell signaling, communication and transport ==> functioning organism

functioning organisms == natural selection + genetic accretion/mutation/epigenetics ==> functional speciation

And the key to successful speciation is the type of accretion/mutations that are agreeable to establishing the emergent valid (stable) state. Natural selection sees to that. Conversely, natural selection weeds out variants that result in unstable (invalid) states.

Courses

From MIT OpenCourseWare

http://ocw.mit.edu/OcwWeb/Biology/index.htm - The entire MIT Biology Curriculum, including:

http://ocw.mit.edu/OcwWeb/Biology/7-012Fall-2004/CourseHome/index.htm - MIT - 7.012 Introduction to Biology

http://ocw.mit.edu/OcwWeb/Biology/7-03Fall-2004/LectureNotes/index.htm - MIT (OCW) - Biology 7.03 - Genetics

http://ocw.mit.edu/OcwWeb/Biology/7-06Spring-2007/CourseHome/index.htm - MIT - 7.06 Cell Biology

http://ocw.mit.edu/OcwWeb/Chemistry/5-08JSpring2004/CourseHome/index.htm - MIT - 5.08J / 7.08J Biological Chemistry

http://ocw.mit.edu/OcwWeb/Biological-Engineering/index.htm - The entire MIT Biological Engineering Curriculum, including:

http://ocw.mit.edu/OcwWeb/Biological-Engineering/20-010JSpring-2006/CourseHome/index.htm - MIT - 20.010J / 2.790J / 6.025J / 7.38J / 10.010J Introduction to Bioengineering (BE.010J)

http://ocw.mit.edu/OcwWeb/Biological-Engineering/20-106JFall-2006/CourseHome/index.htm- MIT - 20.106J / 1.084J Systems Microbiology

http://ocw.mit.edu/OcwWeb/Biological-Engineering/20-440Fall-2004/CourseHome/index.htm- MIT - 20.440 Analysis of Biological Networks (BE.440)

Chapter 5 QA Review

links

http://www.accessexcellence.org/AB/GG/ - From atoms to molecules and cells to tissues - DNA, RNA, proteins, sugars, etc. a great site

http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v409/n6822/full/409860a0_r.html&filetype=&dynoptions= - Human Geneome

http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v420/n6915/full/nature01262_fs.html - Mouse Genome

http://www.phrap.org/compbio/mbt599/ - Lecture slides from a graduate course on genomics and protein sequence analysis, with tons of links to other relevant courses

http://www.nimr.mrc.ac.uk/MillHillEssays/1996/morphgen.htm - Nice article on morphogens

http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v391/n6664/full/391225a0_r.html - Nice article on Hox gene variation and evolution

http://drnelson.utmem.edu/MHEL.hox.html - More on Hox complex

http://www.hms.harvard.edu/news/releases/0200dymecki.html - Nice article on gene expression and limb development

http://life.bio.sunysb.edu/morph/workshops/cambridge98.html - Workshop proceedings: The control of size and shape in skeletal morphogenesis

http://www.iam.ubc.ca/%7Estan/Thesis/Thesis/thesis.htm - Detailed work on the morphogenesis of Dictyostelium discoideum slugs

http://www.genome.gov/glossary.cfm - Talking Glossary of Genetic Terms

http://opbs.okstate.edu/%7Emelcher/MG/MG01.html - Molecular genetics

http://opbs.okstate.edu/%7Emelcher/MG/MGW4/MG42.html - DNA analysis

http://www1.imim.es/courses/SeqAnalysis/GeneIdentification/SearchContent/index.html - DNA Composition, Codon Usage and Exon Prediction

http://www1.imim.es/courses/SeqAnalysis/GeneIdentification/GeneIdentification.html - Computational gene identification

http://www.pbs.org/wgbh/nova/sciencenow/3411/02.html - Nova movie on epigenetics - a must see

http://en.wikipedia.org/wiki/Epigenetics - epigenetics at wikipedia

http://en.wikipedia.org/wiki/Mitosis - mitosis asexual cell replication at wikipedia (recommended: mitosis movies at YouTube)

http://en.wikipedia.org/wiki/Meiosis - meiosis sexual cell replication at wikipedia (recommended: meiosis movies at YouTube)

Next: Cells to Reptiles

Previous: History of Evolution

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