Adaptations of neutrality tests

Most of the genetic variation observed within a biological species is generally thought to be evolutionary “neutral” in the sense that it is irrelevant for an individuum whether its genome contains one particular variant or another. Evolutionary biologists, and in the case of the human species anthropologists and medical scientists as well, are by contrast interested in variants which do influence on an individual’s survival and/or its ability to reproduce. Population geneticists try to find such variants by purely statistical methods in the form of tests on neutrality or shortly neutrality tests. In this thesis four publications are reprinted and discussed which are concerned with modifications of existing neutrality tests. Three of them deal with a class of tests relying on the so-called site frequency spectrum. It was shown previously that some of these tests, originally designed on models of constant population size, can be adapted to allow for changes in population size. This is generalized in the first publication to all tests of similar structure. Another aspect of these tests is that they are ignorant with respect to which variant in a sample might evolve non-neutrally. If instead a particular variant is suspected a priori, the tests have to allow for this information by conditioning on the existence of a variant with the observed frequency. The second and third article introduce the concept of a conditional frequency spectrum and derive its first resp. second moments which are necessary for an appropriate extension of the above-mentioned class of tests. The fourth article presents an algorithmic improvement of a neutrality test of a different kind. Here, primarily computational speed was of concern, in order to bear comparison with competing software. Solely applications on human data are presented, which is available in unrivalled abundance, owing to several large-scale genotyping and sequencing projects. The applicability of neutrality tests, however, is not confined to any particular species