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

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