In which we discover how the physical basis of inheritance, DNA, was identified and learn about the factors that influence how DNA encodes genetic information, how that information is replicated and read, how mutations occur and are often repaired, and how such an extravagantly long molecule is organized within such small cells.
One of the most amazing facts associated with Darwin and Wallace's original evolutionary hypothesis was their complete lack of a coherent or accurate understanding of genetic mechanisms. While it was very clear, based on the experiences of plant and animal breeders, that organisms varied with respect to eon another and that part of that variation was inherited, the mechanism by which genetic information is stored and transmitted was not clear and at the time could not have been known. Nevertheless there were a number of hypotheses, some of which relied on supernatural or metaphysical mechanisms194. For example, some thought that evolutionary variation was generated by a type of inner drive or logic within the organism or even the species. This had the comforting implication that evolutionary processes reflected some kind of over-arching design, that things were going somewhere. Well before the modern theory of evolution was proposed in 1859, Jean-Baptiste Lamarck (1744–1829) suggested that inheritance somehow reflected the desires of the parent195. This would have predicted a type of “internally directed” evolution. In contrast Darwin’s model, based on random variations in the genetic material, seemed more arbitrary and unsettling. It implied a lack of an over-arching purpose to life in general, and human existence in particular.
Another surprising realization is that modern genetics had its origins in the work of Gregor Mendel (1822–1884). He published his work on sexually reproducing peas in 1865, shortly after the introduction of the modern theory of evolution. Since Darwin published revised editions of “On the Origin of Species” through 1872, one might ask why did he not incorporate a Mendelian view of heredity into his theory? The simplest explanation would be that Darwin was unaware of Mendel’s work - in fact, the implications of Mendel’s work were largely ignored until the early years of the 20th century. One might ask why was the significance of Mendel’s observations not immediately recognized? It turns out that Mendel’s conclusions were quite specialized and could be attributed to design details of his experiments and his choice of organism. Mendel carefully selected discrete traits (phenotypes) displayed by the garden pea Pisum sativum: smooth versus wrinkled seeds, yellow versus green seeds, grey versus white seed coat, tall versus short plants, etc. In the plants he used, he found no intermediate versions of these traits. In addition, these traits were independent, the presence of one trait did not influence any of the other traits he was considering. Each was controlled (as we now know) by variation at a single genetic locus (position or gene). The vast majority of traits, however, do not behave in this way. Most genes play a role in a number of different traits and a particular trait is generally controlled (and influenced) by many genes. Allelic versions of multiple genes interact in complex and non-additive ways. For example, the extent to which a trait is visible, even assuming the underlying genetic factor is present, can vary dramatically depending upon the rest of an organism’s genotype. Finally, in an attempt to established the general validity of his conclusions Mendel examined the behavior of a number of other plants, including hawkweed. Unfortunately, hawkweed uses a specialized, asexual reproductive strategy, known as apomixis, during which Mendel’s laws are not followed196. This did not help reassure Mendel or others that his genetic laws were universal or useful. Subsequent work, published in 1900, led to the recognition of the general validity of Mendel’s basic conclusions197.
Mendel deduced that there are stable hereditary "factors" - which became known as genes - and that these genes are present as discrete objects within an organism. Each gene can exist in a number of different forms, known as alleles. In many cases specific alleles (versions of a gene) are associated with specific forms of a trait or the presence or absence of a trait. For example, whether you are lactose tolerant or intolerant as an adult is influenced by which allele of the MCM6 gene you carry. The allele that promotes lactose tolerance acts to maintain the expression of the LCT gene; the LCT gene encodes the enzyme lactase, which must be expressed for an organism to digest lactose198. When a cell divides, its genes must be replicated so that each daughter cell receives a full set of genes (a genome). The exact set of alleles a cell inherits determines its genotype (note, words like genomes and genotypes are modern terms that reflect underlying Mendelian ideas). Later it was recognized that sets of genes are linked together in a physical way, but that this linkage is not permanent - that is, processes exist that can shuffle linked genes (or rather the alleles of genes).
In sexually reproducing (as opposed to asexual or clonal) organisms, like the peas that Mendel originally worked with, two copies of each gene are present in each somatic (body) cell. Such cells are said to be diploid. During sexual reproduction, specialized cells (known as germ cells) are produced; these cells contain only a single copy of each gene and are referred to as haploid (although monoploid might be a better term). Two such haploid cells (typically known as egg and sperm in animals and ovule and pollen in plants), derived from different parents, fuse to form a new diploid organism. In a population there are typically a number of different alleles for each particular gene, and many thousands of different genes. An important feature of sexual reproduction is that the new organism reflects a unique combination of alleles inherited from the two parents. This increases the genetic variation within the population, which enables the population (as opposed to specific individuals) to deal with a range of environmental factors, including pathogens, predators, prey, and competitors. It leaves unresolved, however, exactly how genetic information is replicated and how new alleles form, how information is encoded, regulated, and utilized at the molecular, cellular, and organismic levels.
- It is perhaps worth reading Evolution in Four Dimensions (reviewed here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1265888/) which reflects on the factors that influence selection.
- Apomixis in hawkweed: Mendel's experimental nemesis: http://www.ncbi.nlm.nih.gov/pubmed/21335438