Population genetics for higher education

Population genetics is the study of genetic variation within populations, and involves the examination and modelling of changes in the frequencies of genes and alleles in populations over space and time. Many of the genes found within a population will be polymorphic- that is, they will occur in a number of different forms (or alleles). Mathematical models are used to investigate and predict the occurrence of specific alleles or combinations of alleles in populations, based on developments in the molecular understanding of genetics, Mendel's laws of inheritance and modern evolutionary theory. The focus is the population or the species - not the individual.

The collection of all the alleles of all of the genes found within a freely interbreeding population is known as the gene pool of the population. Each member of the population receives its alleles from other members of the gene pool (its parents) and passes them on to other members of the gene pool (its offspring). Population genetics is the study of the variation in alleles and genotypes within the gene pool, and how this variation changes from one generation to the next.

Factors influencing the genetic diversity within a gene pool include population size, mutation, genetic drift, natural selection, environmental diversity, migration and non-random mating patterns. The Hardy-Weinberg model describes and predicts a balanced equilibrium in the frequencies of alleles and genotypes within a freely interbreeding population, assuming a large population size, no mutation, no genetic drift, no natural selection, no gene flow between populations, and random mating patterns.

In natural populations, however, the genetic composition of a population's gene pool may change over time. Mutation is the primary source of new alleles in a gene pool, but the other factors act to increase or decrease the occurrence of alleles. Genetic drift occurs as the result of random fluctuations in the transfer of alleles from one generation to the next, especially in small populations formed, say, as the result adverse environmental conditions (the bottleneck effect) or the geographical separation of a subset of the population (the founder effect). The result of genetic drift tends to be a reduction in the variation within the population, and an increase in the divergence between populations. If two populations of a given species become genetically distinct enough that they can no longer interbreed, they are regarded as new species (a process called speciation).

In many cases, the effects of natural selection on a given allele are directional. The allele either confers a selective advantage, and spreads throughout the gene pool, or it confers a selective disadvantage, and disappears from it. In other cases, however, selection acts to preserve multiple alleles within the gene pool and a balanced equilibrium is observed. This situation, labelled balanced polymorphism, can arise because of a selective advantage for individuals heterozygous for a given allele. For example, the disease sickle cell anaemia is caused by a mutation in one of the genes responsible for the production of haemoglobin. Individuals with two copies of the mutant gene for sickle haemoglobin (HbS/HbS) develop the disease. Individuals that are heterozygous - one copy of the sickle gene and one copy of the normal gene (HbS/HbA) - are carriers of the condition. It is believed that these heterozygous individuals are more resistant to malaria than individuals homozygous for the normal gene (HbA/HbA), and that this selective advantage maintains the presence of the HbS gene in the population. As a result of balanced polymorphism, the gene pools of most populations contain a number of deleterious alleles that reduces the overall fitness of the population (known as the genetic load).

Genetic variation within populations and species can now be analysed at the level of nucleotide sequences in DNA (genome analysis) and the amino acid sequences of proteins (proteome analysis). The genetic differences between species can be used to infer evolutionary history, on the basis that the closest relatives will have gene pools that are most similar. Recent advances in the sequencing of genomes, allied to computer-based techniques for storing and comparing this information, have led to the construction of detailed evolutionary trees. The use of molecular clocks - nucleotide sequences (or amino acid sequences) in which evolutionary change accumulates at a constant rate - allows dates to be attached to the points at which populations start to diverge to form new species. These approaches are also proving useful in other useful areas (for example, in tracing the transmission routes of infectious diseases).