More generally, we know from genome sequences that the various parts of genes—both their individual exons and their regulatory elements—have served as modular elements that have been duplicated and moved about the genome to create the great diversity of living things. Thus, for example, many present-day proteins are formed as a patchwork of domains from different origins, reflecting their complex evolutionary history (see Figure 3–17).
Neutral mutations Often Spread to become Fixed in a Population, with a Probability That Depends on Population Size
In comparisons between two species that have diverged from one another by millions of years, it makes little difference which individuals from each species are
Figure 4–77 Schematic view of an antibody (immunoglobulin) molecule.
This molecule is a complex of two identical heavy chains and two identical light chains. Each heavy chain contains four similar, covalently linked domains, while each light chain contains two such domains. Each domain is encoded by a separate exon, and all of the exons are thought to have evolved by the serial duplication of a single ancestral exon.
compared. For example, typical human and chimpanzee DNA sequences differ from one another by about 1%. In contrast, when the same region of the genome is sampled from two randomly chosen humans, the differences are typically about 0.1%. For more distantly related organisms, the interspecies differences outshine intraspecies variation even more dramatically. However, each “fixed difference” between the human and the chimpanzee (in other words, each difference that is now characteristic of all or nearly all individuals of each species) started out as a new mutation in a single individual. If the size of the interbreeding population in which the mutation occurred is N, the initial allele frequency for a new mutation would be 1/(2N) for a diploid organism. How does such a rare mutation become fixed in the population, and hence become a characteristic of the species rather than of a few scattered individuals?
The answer to this question depends on the functional consequences of the mutation. If the mutation has a significantly deleterious effect, it will simply be eliminated by purifying selection and will not become fixed. (In the most extreme case, the individual carrying the mutation will die without producing progeny.) Conversely, the rare mutations that confer a major reproductive advantage on individuals who inherit them can spread rapidly in the population. Because humans reproduce sexually and genetic recombination occurs each time a gamete is formed (discussed in Chapter 5), the genome of each individual who has inherited the mutation will be a unique recombinational mosaic of segments inherited from a large number of ancestors. The selected mutation along with a modest amount of neighboring sequence—ultimately inherited from the individual in which the mutation occurred—will simply be one piece of this huge mosaic.
The great majority of mutations that are not harmful are not beneficial either. These selectively neutral mutations can also spread and become fixed in a population, and they make a large contribution to evolutionary change in genomes. For example, as we saw earlier, they account for most of the DNA sequence differences between apes and humans. The spread of neutral mutations is not as rapid as the spread of the rare strongly advantageous mutations. It depends on a random variation in the number of mutation-bearing progeny produced by each mutation-bearing individual, causing changes in the relative frequency of the mutant allele in the population. Through a sort of “random walk” process, the mutant allele may eventually become extinct, or it may become commonplace. This can be modeled mathematically for an idealized interbreeding population, on the assumption of constant population size and random mating, as well as selective neutrality for the mutations. While neither of the first two assumptions is a good description of human population history, study of this idealized case reveals the general principles in a clear and simple way.