8 Genes become you
8.1 Genes and behaviour
In the preceding sections many different proteins have been mentioned. These proteins are the receptors, signals, channels, enzymes, transporters, structural components and transcription factors that enable the nervous system to grow and function. Other proteins (e.g. the actin in muscles) are involved in making limbs move and sense organs function. Any and all behaviour is dependent on these proteins. And as each of these myriad proteins is the product of a gene, it follows that any and all behaviour is dependent on many genes. The word used to describe this dependence on many genes is polygenic. No behaviour is the product of a single gene. Yet there remains pressure in the popular press and to some extent in society at large, to make just this link; to identify the gene for ***** (you could insert any topical/aberrant behaviour here, e.g. obesity, schizophrenia, etc.). There are two main reasons for this pressure. The first reason is the extraordinary success the medical profession has had in associating particular gene variations (alleles) with certain medical conditions. (Some specific conditions are discussed later in this section.) So, the argument goes, if some conditions, then all conditions; if all conditions, then all behaviours. The second reason for the pressure is that to associate an allele with a condition somehow concludes the quest for the cause of the condition; a bit like a guilty verdict in a murder inquiry. Yet associating an allele with a condition does nothing of the sort, it does not conclude the quest for the cause of the condition. Explanation and treatment require an understanding of what the allele, or more specifically its product, does. Finding the allele is better likened to finding a body, than a guilty verdict; you no longer have a missing person, but you have a long way to go to solve the mystery. The list of the kinds of things that proteins can do is long. In addition, it is also often the case that the product of a single allele, a single protein, can affect many biochemical pathways, and affect many components within the body, a situation known as pleiotropy (for example, see Wilson's disease, Section 8.2). Finding an allele associated with a particular disease is an important clue as to the causes of the disease, but it does not necessarily solve the mystery.
All of the myriad proteins mentioned in previous sections, the receptors, signals, channels, enzymes, transporters and transcription factors, are products of their respective alleles. New alleles can arise by mutation. When this happens, the new alleles often produce defective proteins by which is meant simply that the protein cannot do its job and as a consequence the phenotype is affected. Amadeus Mozart, Nelson Mandela and Paula Radcliffe may all have had their phenotype affected by defective proteins. But usually the exceptionally gifted are not subject to genetic studies. In contrast, and in the examples that follow, it is the adversely affected phenotype that is subject to genetic study.
Sometimes the absence (occasionally the presence, but more usually the absence) of a particular protein has an effect on an organism that is very conspicuous. Most frequently the effect of the absence is lethal. For those absences that are not lethal, the effect may be conspicuous because it alters the organism's composition, its shape, its response to stimuli, its colour or its behaviour. In such cases the effect of the single missing protein penetrates through the effects of all the other proteins in the body and manifests itself as a conspicuous character or set of characters. The character(s) can be said to be strongly associated with a particular protein and hence a particular gene. And depending on the extent of the effect, the organism may be considered to be simply unusual, or unusual and adversely affected, i.e. diseased. (Unusual domestic animals may go on to found new breeds, or varieties, or strains: consider the range of varieties of dogs, for example.) Where absences have been induced in some way, the process of looking for the effects is called a genetic screen. People who are unusual and adversely affected by being so will turn to the medical profession for help, and it is here that the quest for a gene strongly associated with the character might begin, for example with a family history or twin studies (see Box 2).
Box 2 Finding genetic correlates in people
There are four main ways in which scientists look for genetic correlates of human characteristics. Those characteristics can be anything from an extra digit on the hands through to behavioural choices (e.g. thrill seekers). These four ways are families, twins, adoption and genetic markers.
Families Characters that are consistently present in some families and not others, i.e. characters that appear to be inherited, are strong candidates for a genetic search. Tracing family histories and identifying individuals with and without the character can reveal the pattern of inheritance. The genetic basis of Huntington's disease was identified using extensive family pedigrees.
Twins Identical twins have an identical genome. Any character that one twin has, the other twin must also have if the character is strongly associated with a particular gene. There should be what is referred to as a high level of concordance between the twins. Where only some pairs of identical twins share a character, there is said to be discordance and the character is said to be strongly influenced by environmental factors.
Non-identical twins do not share a genome, indeed are no more genetically similar than ordinary siblings, but do share a family environment. Comparisons of concordance between identical and non-identical twins for a character give some indication of the extent to which the character is associated with particular genes.
Adoption Identical twins share a family environment and so concordance for a character could be due to their shared circumstances rather than their shared genome. Examining concordance where twins have been separated very early in life, usually by adoption into different families, allows the contribution of genome and environment to be distinguished. Note though that adoptive families must meet certain criteria set by the adoption agencies, and so adoptive families may share a number of qualities.
Genetic markers These are short sections of ‘junk’ DNA which can be identified biochemically. If two people have one of these short sections in common, then, because of the way in which DNA is inherited, it is likely that they have alleles adjacent to the short section in common too. The short section ‘marks’ alleles for further investigation.
The three examples that follow in Sections 8.2 to 8.4 have been chosen to reveal different levels of the complex relationship between genome and phenotype.