"Molecular genetics has revealed a wealth of detail about many biological systems. Still current ignorance is vaster than current knowledge. Nothing in the human-made world rivals the complexity and diversity of living things. There are, in nature, concepts that no one has yet imagined. Looking over the past 150 years--at the tiny garden at Brno, the filthy fly room at Columbia, the labs of the New York Botanical Garden, the basement lab at Stanford, and the sun-drenched early gatherings at Cold Spring Harbor--it seems that the fringes, not the mainstream, are the most promising places to discover revolutionary advances..." Paul Berg & Maxine Singer, "Inspired choices", Science282:873-874 (30 October 1998).
Brief Outline
Central questions in evolution are: What variation exists? How is that variation inherited? And where does new variation comes from? These remain fundamental issues. No satisfactory answers were available in Darwin's time, and current answers are far from complete.
At about the same time that Darwin was writing up his Origin, Mendel was conducting experiments with pea plants and discovering evidence for genetic factors, later named genes, which follow Mendel's Laws of segregation (of alleles into gametes) and independent assortment (of unlinked genes).
Mendel was fortunate in working with several unlinked characters (associated with different chromosomes) so his results were not complicated by linkage. Mendel himself did not realize the profound generality of his results, partly because his later work with hawkweeds did not support his pea results (because of peculiarities with hawkweeds, including parthenogenetic reproduction).
Note that Mendel's "factors" were hypothetical entities invented to provide a mathematically simple explanation for observable phenotypes.
Cytology, cell division and chromosomes
The 1800s saw much intense study of cells, especially observations concerning the mysteries of cell division and reproduction. Nuclei were recognized as having some special significance. The dance of the chromosomes during mitosis and meiosis was described 1870s and 1880s. The precision of these actions was compelling, and suggested to several biologists a significant role for chromosomes in heredity.
E.B. Wilson, 1895: "These facts justify the conclusion that the nuclei of the two germ-cells are in a morphological sense precisely equivalent, and they lend strong support to Hertwig's identification of the nucleus as the bearer of heredity qualities. The precise equivalence of the chromosomes contributed by the two sexes is a physical correlative of the fact that two sexes play, on the whole, equal parts in hereditary transmission, and it seems to show that the chromosomal substance, the chromatin,is to be regarded as the physical basis of inheritance. Now, chromatin is known to be closely simlar to, if not identical with, a substance ... which analysis shows to be a tolerably definite chemical composed of nucleic acid (a complex organic acid rich in phosphorus) and albumin [i.e., protein]. And thus we reach the remarkable conclusion that inheritance may, perhaps, be effected by the physical transmission of a particular chemical compound from parent to offspring."
Mapping genes onto chromosomes
Rediscovery of Mendel's laws near the turn of the century led quickly to the realization that the behavior of chromosomes during meiosis and fertilization exactly matches expectations for Mendel's hypothetical "factors". Therefore, maybe Mendel's factors were real, physical entities somehow embodied by chromosomes. This was soon followed by discovery of linkage groups (i.e., each chromosome contains many genes) and of recombination within linkage groups, correlated with the physical crossing-over of the chromosomes. That in turn led to an understanding of genes as arranged linearly, like "beads-on-a-string" along the chromosomes.
This all sounds easy. But the amount of painstaking observation that was needed to establish the physical behavior of chromosomes and the corresponding behavior of genetic factors is truly astounding.
The words gene, genotype, and phenotype were coined by Johannsen as names for abstract concepts rather than for discrete, well-defined chemical entities. Population genetics, and much modern evolutionary theory, has adopted this abstract concept, and the associated genes-as-beads-on-a-string model of chromosome structure, and carried it forward rather uncritically. The one-gene-one-enzyme model from prokaryotic genetics reinforced this concept. But it turns out that a simple and completely satisfactory definition for gene in molecular terms may not be possible (see below).
Furthermore, the abstract concept of "gene" is widely extended to the concept of "hereditary trait", so that any inherited character is commonly presumed to have an associated gene that behaves according to Mendelian rules. This has created many opportunities for misunderstanding (and abuse related to eugenics).
Mutation has acquired a modern understanding quite different from its original meaning. According to the Oxford English Dictionary, the basic meaning is:
Even in biology, the term has itself undergone a fairly radical transformation over the past 100 years. Again, from the OED:
Here are some examples of this usage:
Mendelism, mutationism and the Modern Synthesis
Throughout the revival of Mendelism in the first decades of the 20th Century, the Darwinian concept of slow, gradual transformation was replaced by the idea of species origination by sudden mutation ("mutationism") or leaps (saltations, hence "saltationism").
Our modern view of evolution began when the principles of Mendelian genetics were combined statistical population genetics, together with the realization that mutations could have small effects as well as large. The result was the Modern Synthesis, also sometimes called neo-Darwinism. The great successes of the Modern Synthesis have led to a rather cavalier disregard for some of the prior problems in evolutionary genetics, particularly the still unresolved mysteries of genome evolution. Richard Goldschmidt introduced the concept of hopeful monsters in an unsatisfactory attempt to engage such problems; modern molecular genetics may still need concepts of large-scale genetic reorganization.
The most recent "revolution" in genetics came with the discovery of the chemical structure of DNA, which spectacularly resolved many fundamental problems regarding the nature of the hereditary material. The wonderful growth of knowledge about the structure and function of DNA over the past fifty years has largely obscured the fact that quite a few fundamental questions remain largely unanswered at the beginning of the 21st century. We still don't understand development. (How are complex structures encoded?). We still don't understand mutation. (What is the source of the favorable variations that lead to adaptive macroevolutionary novelty?) And we still don't really understand speciation. (How do the genetic/structural differences that separate species actually arise?) Yet all of these were already important questions at the end of the 1800s.
You should know the basic genetics, as reviewed in this chapter, which underlies all of the chapter subheadings. The following comments highlight the basic facts and call your attention to some deeper issues which are often overlooked, especially in simplified undergraduate texts.
Our scientific understanding of genetics may appear vast. But consider the following task, as a measure of how limited this understanding actually is: Given the genetic specification (complete DNA sequence of the entire genome) for some ancestral organism, design the specific mutations needed to accomplish some specific macroevolutionary transformation (e.g., converting fish fins into legs into feathered wings, or the brain of a marine annelid into the brain of a spider that "knows" how to weave a silken orb web to catch flying insects).
2.1 "Inheritance is caused by DNA molecules, which are physically passed from parent to offspring."
This is a central concept in biology. Along with evolution, one might (arguably) say it defines the theoretical core of biology. Make sure you know what a chromosome is, appreciate how the DNA double-helix base-pair structure is related to replication, and understand the relevance of this information for reproduction, including mitosis, meiosis and fertilization (zygote formation). Know the names of the purines, adenine and guanine, and the pyrimidines, thymine and cytosine, and which pairs with which (A with T, C with G).
Do note that the word "caused" is used rather too casually in this context. Causation is a deep idea in philosophy. Evolutionary biology takes as its goal the tracing of a multitude of causal factors, many of which are complementary or supplementary to the occurrence of any particular DNA molecules. But as long as you remain aware that DNA molecules are not the ONLY cause of inheritance, we can move on.
2.2 "The DNA structurally encodes the information used to build the body's proteins."
Make sure that you understand how proteins are represented by codons, including the significance of codon position for each base (e.g., How is the significance of third position substitutions any different from those at second position?).
But note again, as with "caused" above, the term encodes hides some rather deep philosophical issues. For example, it is very difficult to break the circle in which DNA replication, transcription and translation depend critically on proteins and on prior cell organization, so which "codes for" which is arguable. Such concerns become especially critical for certain problems such as the origin of life, or for understanding how complex features (eyes, wings, instincts) are represented genetically. This assertion is, nonetheless, fairly conventional and superficially harmless, and for present purposes we may move on.
2.3 "The information in the DNA is decoded by transcription and translation."
Certainly, some information in the DNA is decoded by transcription and translation, namely the amino acid sequence of proteins.
But, somehow, development also decodes information about the structure and instinctive behavior of a complex organism. By omitting mention of this mystery, statements such as this one by Ridley risk implying that the information needed to build an organism is no more than a list of protein sequences. This presumption is dangerously naive.
An organism is much more than a bag of proteins. Imagine a book written as a vocabulary list followed by a set of numbers which specified how the words should be arranged (how many times each word appeared, and in what order). If we decoded the numbers, we could print out the entire book in normal form. But if we only knew the vocabulary list, what would we know of the plot? Knowing all the amino acid sequences of all the proteins encoded by all the structural genes in the genome [the goal for the Human Genome Project] is roughly akin to having a vocabulary list for a book. Without the proteins, there could be no body; without the words, there could be no book. But just as the book includes vastly more information, in the form of how those words are used, so also the genome includes vastly more information in the developmental program which guides the expression of the genes. And science has hardly even begun to understand how that information is decoded.
There is a discipline of biology, sometimes labelled evo-devo (short for evolution and development) dedicated to exploring the evolutionary implications of developmentally-decoded genetic information.
2.4 "Mutational errors may occur during DNA replication and repair."
Once again, this is a very conventional statement. You should understand the various types of mutation, including effects on DNA structure and likely protein and phenotypic consequences. Know the difference between transition and transversion. Be able to distinguish between DNA damage, replication errors, and failures of DNA editting or repair.
But do note the word error has connotations which may obscure matters of significance, such as the fact that some features of genetic organization appear designed to promote certain classes of mutation. The randomness of mutation is also a matter that is rather difficult to define with any precision. The best -- most theoretically sound -- meaning for "random" in relation to mutation is that specific mutations are not directed toward any particular advantageous phenotype.
Conventional wisdom holds that all mutations are errors, or failures in a system that has evolved for maximal fitness through maximal replication fidelity. This same conventional wisdom also presumes that most mutations are either deleterious or neutral. Your professor is among a small but growing community of biologists who understand that at least some mechanisms of mutation can yield a sufficiently high percentage of beneficial mutations so that the mutation process itself can confer selective advantage. For further information, see Recent Items below or visit Dr. King's webpage to find additional references and summaries of current research.
2.5 "The rates of mutation can be measured and estimated."
Although much work has been done on mutation rates, please note that we do NOT have anything like a mathematical theory of mutation. Knowing accurately the causes and rates for various classes of mutations would be invaluable in many areas of evolutionary biology, but we do NOT have that knowledge.
There are many different classes of mutation (e.g., point substitution; point insertion or deletion; various sizes of deletion, insertion, inversion and translocation), all of which may occur at very different rates. Within any given class of mutation, different sites in the genome have very different mutation rates. Many different measures are used to assess "mutation rates", including alteration of a trait, recovery of a lost trait, or appearance of a particular type of point mutation at a particular base position. Mutation rates may be reported as mutations per genome, per locus (meaning gene) or per base-pair. They can also be reported per year or per generation or per cell division. All of these considerations make reporting and comparison of mutation rates a rather problematic enterprise.
Conventional wisdom holds that all mutation rates are very low . Your professor is among a small but growing community of biologists who understand that some genomic sites havea evolved much higher mutation rates, and that such site-specific rates can confer selective advantage. For further information, see Recent Items below or visit Dr. King's webpage to find additional references and summaries of current research.
2.6 "Diploid organisms inherit a double set of genes."
Understand the basic terminology for describing Mendelian inheritance in diploid, sexually reproducing organisms, including diploid, haploid, gamete, zygote, gene, locus, dominant, recessive, homozygote, heterozygote, genotype, phenotype.
The words gene, genotype, and phenotype were all introduced by Johannen in 1911, long before any modern understanding of gene. These terms are most useful for describing simple genetic differences governed by single, discrete loci. But genetic reality is actually quite complex, such that most traits are governed by manay genes (and by external, environmental influences) and many genes influence many traits. Further, the concept of gene is itself rather poorly defined, such that Philip Kitcher (see Keller & Lloyd in References) could write "A gene is anything a competent biologist chooses to call a gene." The distinction between genotype and phenotype can also be problematical, as noted by Lewontin (again, see Keller & Lloyd in References)
2.7 "Genes are inherited in characteristic ratios."
This section describes basic Mendelian heredity. Here is one place where the course prerequisite really matters. If you are not completely comfortable with the information described here, including linkage and recombination, study until you are. Do the end-of-chapter problems (but note there are some errors in the answers at the back of the book).
2.8 "Darwin's theory would probably not work if there was a non-Mendelian blending mechanism of heredity."
Note that a concept blending inheritance is much more in accord with everyday experience than Mendelian inheritance. We all know from family experience, that parental appearances are often blended, mixed, averaged in offspring. We still use the old terminology when we speak of someone as having "mixed blood" or "mixed ancestry". And such a conceptual view was given legal force in assigning individual persons into racial categories, well into the twentieth century.
Ridley's explanation of selection under blending inheritance may be a bit difficult to follow. Basically it goes like this: With a "standard model" of blending inheritance, combining two different parental traits yields a new heritable trait midway between the two. A beneficial new mutation will quickly be diluted by breeding with the larger population. (At each cross, the value of the new, blended trait will move half-way toward the original pre-mutant value.) By the time selection can "fix" the new trait, its effect will be much reduced. So taking a complete step of evolutionary change, shifting the entire population as far as the original mutation, would require extremely many repeated introductions of the mutation, with many rounds of selection. Therefore, blending inheritance would make natural selection a very inefficient agent of evolution, extremely so in very large populations. (With Mendelian inheritance, on the other hand, a single introduction of a favorable mutation would be enough for selection to yield a full change.)
Darwin's responses to this problem included pointing out that (1) beneficial traits could persist at higher levels if mutants bred among themselves, (2) some traits are dominant and don't blend, and (3) mutations may be frequent enough and recurring, and so difficult to blend out. Remember, Darwin also assumed unlimited time for evolution, while nineteenth century physics suggested time limited to a few tens of millions of years.
Recent Items of relevance to this chapter:
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