Charles Darwin defined evolution as ``descent with modification," a
conceptual model which has held up well over the years
. Darwin's ideas were formed before anyone had any
idea about the nature of heredity. Even after the rediscovery of Mendel
in 1900, the connection between Mendelian inheritance and Darwinian
evolution was not immediately obvious, and there were bitter disagreements
between the opposing camps (Mendelians, studying discrete traits, and
biometricians, studying continuous, ``Darwinian"
variation) [11]. Eventually, however, empirical geneticists
began to realize what Mendel had seen initially, that numerous ``factors",
each of small effect, could produce apparently continuous phenotypic
variation. The conflict was finally (mostly) resolved by R.A.
Fisher [3], who developed the mathematical theory of the
relationship between multilocus factors and phenotypic variance. With
Fisher's paper, and contributions of others such as Sewall
Wright[14,15] and J.B.S. Haldane[6],
Darwin's definition could be framed in terms of genetics: individuals
pass their genes to offspring (descent), genes are modified within
individuals (mutation to new alleles), and the genetic composition of
populations and species are modified through changes in the frequencies of
particular alleles.
Much of the population genetics theory subsequently developed in the 1930's and 40's is relevant and applicable to problems today, even though the fundamental mathematical and philosophical framework was laid down before DNA had been positively identified as the hereditary molecule. Molecular evolutionary studies are a relatively recent development, sparked by the massive amounts of detailed genetic knowledge emerging from technological advances in molecular biology. What access to molecular-level information on patterns of genetic variation has done, first, is to help to make more quantitative use of the older theory. It has also demanded the development of new theory, specifically geared to help understand the patterns of variation found at the molecular level. The most familiar of these, the neutral theory (Kimura [9], see Section 3.1), has achieved preeminent status-- but not universal acceptance (Gillespie [5]) as an appropriate null hypothesis for molecular evolution.
The fundamental premise behind molecular evolutionary studies is that within an organism's (macro-)molecules (DNA, RNA, proteins) there lies an imprint or record of the evolutionary processes that shaped those molecules. The practice of molecular evolutionary studies is to try to reconstruct the history of past processes, and of phylogenetic relationships among genes and species, from that imprint.