TABLE 7-3 Basic Theoretical Questions to Be Addressed

Number of genes specifying various aspects of the life course

Location of genes specifying various aspects of the life course

Size of effects specified by each gene

Interactions between genes

Effects of individual genes on more than one aspect of the life course

Identification of and characterization of genes involved in these events

Issues in Evolutionary Theory and in Demography That Can Be Addressed by QTL Mapping

Gene interactions have been postulated to be important in many aspects of evolution and speciation. It is a general assumption in much evolutionary theory that most genes affect many different traits (pleiotropy). Antagonistic pleiotropy has been suggested as a mechanism for maintaining genetic variation and as a mechanism for the evolution of genes that limit life span, trading off survival with some early fitness trait.

In summary, the value of QTL mapping is that it allows the assessment of effects resulting from individual loci rather than the genome as a whole. More specifically, there are a number of questions that QTL mapping can answer (Table 7-3). The genes, their location, and the amount of genetic variation explained by each can be determined by QTL mapping. Most importantly, it is possible to gain some insight into the interactions between and among these QTLs in specifying their respective phenotypes. It is also possible to identify QTLs that are pleiotropic in their action, affecting more than one stage or aspect of life history or demography.

Cloning The Genes

There is an "ultimate question" which one hopes to eventually answer in these mapping studies: "What is the nature of the genes responsible for these life extensions?" This same ultimate question was asked almost 50 years ago when quantitative genetics and Mendelian genetics made their great rapprochement. It is still not clear if the "mutations" identified and used to such good measure by Drosophila and nematode geneticists are stronger alleles of the same genes underlying quantitative traits. The cloning of the gerontogenes themselves should allow us to answer this question directly.

The only successful cloning of gerontogenes based primarily on their extended survival has been in yeast. These studies have focused on the limited proliferative life span of individual yeast cells (Jazwinski, 1996), as well as on the limited length of viability of these cells in stationary phase (Kennedy et al., 1995). The mutants (UTH1-UTH4 ) isolated by Kennedy et al. (1995) had increased life expectancy in stationary culture. One mutant gene was cloned by complementation of its associated sterility phenotype and shown to be a mutation in SIR4, a gene involved in transcriptional silencing.



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