Our understanding of the causes of molecular evolution is not as certa
in as it was a decade ago when Kimura's neutral theory appeared to exp
lain major features of DNA conservation and change. The last ten years
have seen the development of empirical approaches and statistical tes
ts for detecting selection in DNA and a proliferation of data that cha
llenge our current understanding of the molecular evolutionary process
. We begin this review with a discussion of protein polymorphism and d
ivergence: two major areas of research where the strictly neutral mode
l cannot explain general patterns in the data. We then present a surve
y of statistical methods for detecting positive selection, which inclu
des tests for balancing selection, for sequence convergence, and for u
nusually high rates of evolution that cannot be accounted for by neutr
al models. Finally, we present findings of a number of groups working
on within- and between-species variation in Drosophila: These highligh
t the importance of adaptive evolution, purifying selection, and recom
bination in understanding levels and patterns of nucleotide variation.