The Importance of Variation in Evolution

1. Evolution of genomes

2. Descent with modification At the most abstract level, evolution can be defined as descent with modification. We have seen how DNA replication ensures a mostly faithful passing of the genome to progeny. But if this replication were 100% accurate, no modification whatsoever could occur in asexual species, the variability in sexually reproducing organisms would be limited to the possible recombinations of a fixed number of alleles.

3. Descent with modification However, the variety we see in nature is MUCH greater than what could be achieved by recombination alone. Most modifications in the course of evolution are due to copying errors in the process of DNA replication called mutations . These copying errors provide the raw material that natural selection acts on. Deleterious mutations tend to be eliminated by selection, favorable mutations tend to spread through the population and eventually replace the original ( wildtype ) allele.

4. Descent with modification Many mutations appear to be neither deleterious nor favorable. The change in frequency of individuals that carry such neutral mutations is largely determined by genetic drift. It is not always clear whether a mutation is deleterious, favorable, or neutral. Due to epistatic interactions of different loci in the genome, a mutation on one locus can confer a selective advantage when in the company of one set of alleles and can confer a disadvantage when in the company of a different set of alleles.

5. Types of mutations For the development of good models of molecular evolution it is useful to distinguish between different types of mutations. I will make here the major distinction between mutations on a local scale and mutations on a global scale , the former being ones that can be described by looking at a stretch of a few thousand base pairs, the latter being ones on the scale of the whole genome. It should be pointed out that the distinction is made for modeling purposes only and is clear cut in some and artificial in other cases.

6. Mutations on a local scale On a local scale, there are for types of mutations: z Point mutations z Insertions of a stretch of DNA z Deletions of a stretch of DNA z Inversions of a stretch of DNA It is often difficult to decide whether a deletion or an insertion has occurred relative to the genome of a common ancestor. Insertions and deletions are therefore often lumped together under the name indels.

7. Tandem repeats Another effect of local mutations (most likely due to DNA-slippage or to unequal crossover) is the frequent occurrence of tandem repeats , where the same fragment of DNA is repeated in tandem, often many times. Dependent upon the length of the repeated stretch and the number of repeats, geneticists distinguish satellite DNA, minisatellites, and microsatellites.

8. Point mutations Point mutations are the replacement of one nucleotide by another. We distinguish transitions (the replacement of one purine by another or one pyrymidine by another) from transversions (the replacement of a pyrymidine by a purine or vice versa ). Transitions occur much more frequently than transversions.

9. Point mutations If point mutations occur in a coding region, due to the degeneracy of the genetic code, the mutation may or may not alter the sequence of amino acids that is being coded. We distinguish between silent or synonymous mutations and non-synonymous mutation. In the case of the former, a codon for an amino acid is being mutated to another codon for the same amino acid (or one STOP codon for another STOP codon); in the case of the latter, the translation of the codon changes.

10. Mutations on a global scale On the scale of the whole genome, several types of mutations are known to have occurred. For our purposes, the most interesting phenomena are gene duplications and genome rearrangements. Another important effect of evolution on a global scale is the existence of highly repetitive non-coding DNA produced by transposable elements.

11. Genome rearrangements Over the course of evolution, many large-scale genome rearrangements are known to have occurred. This involve such processes as large-scale inversions and transpositions (often involving the movement of genetic material from one chromosome to another) as well as linking or breaking up chromosomes.

12. Gene duplications Gene duplication is a process by which two copies of a parental gene get passed on to the progeny. This process leads to several important phenomena. Some genes simply persist in several copies. Other genes form gene families with each gene having somewhat different functions. In other cases, one copy of the duplicated gene ceases to be expressed and becomes a pseudogene.

13. Orthologous vs paralogous genes In bioinformatics, we often study genes from different organisms that have evolved from a common ancestral gene. Such genes are called homologous genes. If the genes have all evolved from the same copy of the ancestral gene since the most recent duplication of this gene, we speak of orthologous genes , otherwise we speak of paralogous genes.