7.12: Genes and alleles

A gene corresponds to specific sequences of DNA. Different versions of a gene, known as alleles, differ in their DNA sequences. Two alleles of the same gene can differ from one another by as little as one nucleotide pair out of thousands or at multiple positions. Differences between alleles can include sequence changes, deletions, duplications, and insertions. A complicating factor is that a particular gene may encode "products" with multiple functional roles, and a particular trait is generally influenced by multiple genes. A particular allele of a particular gene may influence different functional roles and traits differently, something to keep in mind in the following discussion which, for simplicity’s sake, focusses on a single functional role of a gene product and its influence on a single (simple) trait.

An allele can produce a gene product with completely normal function(s) or no (apparent) functional activity at all, referred to as a null or amorphic allele.The allelic form can have less function than the "wild type" allele (hypomorphic), more function than the wild type (hypermorphic), or a new function (neomorphic). Given that many gene products function as part of multimeric complexes, encoded by multiple genes, and that many organisms (like us) are diploid, there is one more formal possibility, the product of one allele can antagonize the activity of the other - this is known as an antimorphic allele. These different types of alleles were defined genetically by Herbert Muller (1890-1967), who won the Nobel prize for showing that X-rays could induce mutations, new alleles (Appendix 1). The characterization of an allele is typically carried out with respect to how it influences a specific trait. Again, remember that most traits are influenced by multiple genes, and a single gene can influence multiple traits.

The most common version of an allele is often referred to as the wild type allele (← thanks Mercer Mayer), but that is really just because it is the most common. There are often multiple alleles of a particular gene in a population and they all may be equally "normal", although they may influence different traits differently. If there is no significant selective advantage between them, their relative frequencies within a population can drift over time. At the same time, the phenotype(s) associated with a particular allele can be influenced by the alleles present at other genetic loci, known collectively as the genetic background. Since most traits are the results of many genes functioning together, different combinations of alleles can produce different effects. The universe of variation is large. This can make identifying the genetic basis of a trait or a disease difficult, particularly when variation at any one locus may make have only a minor influence on a trait or a disease phenotype. On top of that, stochastic effects together with environmental and developmental differences can outweigh genetic influences on phenotypic outcome. Genetic background effects can lead to a particular allele producing a disease in one person and not another.^[308]

Mutations are the ultimate source of genetic variation – without them evolution would not occur. A mutations can have a number of effects, in particular, they can create new activities. At the same time most mutations reduce or alter the original (and necessary) activity of a gene, an activity than might be essential. Here is an example for how a mutation can be creative. While it is common to think of a particular gene product having a single activity, when examined closely many proteins with catalytic activity can catalyze “off-target” (sometime termed promiscuous) reactions.^[309] A mutation can enhance the off target activity. If that activity is useful, it can influence reproductive success and so be "selected", assuming that the mutation does not disrupt any essential function(s) of the gene product.

Genomic rearrangements, which are mutations because they change genome sequence, can occur during embryonic development.^[310] In the case illustrated here (↓), imagine that an essential but multifunctional gene is duplicated and moved elsewhere in the genome. Now one copy can continue to carry out its original essential function, while the second (new) copy is free to change as long as it does not interfere with the function(s) of the essential gene. While many mutations will negatively effect the duplicated gene, some may increase and refine its favorable ancillary function. A new gene can emerge freed from the need to continue to perform its original function. We see evidence of this type of process throughout the biological world. When a gene is duplicated, the two copies are known as paralogs. Such paralogs can evolve independently.

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