29.1: Introduction

For centuries, biologists had to rely on morphological and phenotypical properties of organisms in order to infer the tree of life and make educated guesses about the evolutionary history of species. Only recently, the ability to cheaply sequence entire genomes and find patterns in them has transformed evolutionary biology. Sequencing and comparing genomes on a molecular level has become a fundamental tool that allows us to gain insight into much older evolutionary history than before, but also to understand evolution at a much smaller resolution of time. With these new tools, we can not only learn the relationship between distant clades that separated billions of years ago, but also understand the present and recent past of species and even different populations inside a species.

In this chapter we will discuss the study of Human genetic history and recent selection. The methodological framework of this section builds largely on the concepts from previous chapters. Most specifically, the methods for association mapping of disease and phylogenetic constructs such as tree building among species and genes, and the history of mutations using coalescence. Having learned about these methods in the last chapter, we now will study how their application can inform us about the relationships, and differences between human populations. Additionally, we will look for how these differences can be exploited to look for signals of recent natural selection and the identification of disease loci. We will also discuss in this chapter what we currently know about the differences between human populations and describe some parameters we can infer that quantify population differences, using only the extent genetic variation we observe. In the study of Human Genetic history and recent selection, there are two principal topics of investigation which are often studied. The first is the history of population sizes. The second is the history of interactions between populations. Questions are often asked about these areas because the answers can often provide knowledge to improve the disease mapping process. Thus far, all present research based knowledge of human history was found by investigating functionally neutral regions of the genome, and assuming genetic drift. The reason that neural regions are employed is because mutations are subject to positive, negative and balancing selection pressure, when they take place on a functional region. Hence investigating a neural regions provides a selection unbiased proxy for the drift between species. In this chapter we will delve into some of the characteristics of selection process in humans and look for patterns of human variation in terms of cross species comparisons, comparison synonymous and non-synonymous mutations, and haplotype structure.