A Genomewide Assessment of Inbreeding Depression: Gene Number, Function, and Mode of Action

Abstract

Although the genetic basis of inbreeding depression is still being debated, most fitness effects are thought to be the result of increased homozygosity for recessive or partially recessive deleterious alleles rather than the loss of overdominant genes. It is unknown how many loci are associated with inbreeding depression, the genes or gene pathways involved, or their mode of action. To uncover genes associated with variation in fitness following inbreeding, we generated a set of inbred lines of Drosophila melanogaster for which only the third chromosome varied among lines and measured male competitive reproductive success among these lines to estimate inbreeding depression. Male competitive reproductive success for different lines validated our prediction that equally inbred lines show variation in inbreeding depression. To begin to assess the molecular basis of inbreeding depression for male competitive reproductive success, we detected variation in whole-genome gene expression across these inbred lines with commercially available high-density oligonucleotide microarrays. A total of 567 genes were differentially expressed among these inbred lines, indicating that inbreeding directly or indirectly affects a large number of genes: genes that are disproportionately involved in metabolism, stress and defense responses. Subsequently, we generated a set of outbred lines by crossing the highest inbreeding depression lines to each other and contrasted gene expression between parental inbred lines and F(1) hybrids with transcript abundance as a quantitative phenotype to determine the mode of action of the genes associated with inbreeding depression. Although our results indicated that approximately 75% of all genes involved in inbreeding depression were additive, partially additive, or dominant, about 25% of all genes expressed patterns of overdominance. These results should be viewed with caution given that they may be confounded by issues of statistical inference or associative overdominance.

Proteomic characterization of a temperature-sensitive conditional lethal in Drosophila melanogaster

“…In addition, molecular functional characterization of inbreeding-related phenomena may contribute to resolve the long-standing debate about the relative contributions of major genes to inbreeding depression. Recent evidence suggests that inbreeding depression is caused by a few major genes that in turn affect many other genes (Ayroles et al, 2009). Analyses of temperature-sensitive mutations are of relevance in relation to predicting the effect of global warming, besides also being important in relation to inbreeding by environment interactions (Parmesan and Yohe, 2003).…”

“…Understanding the genetic basis of inbreeding depression is, therefore, crucial for evaluating the evolutionary consequences of inbreeding. Recent evidence has shown that a large amount of inbreeding depression is caused by complex epistatic interactions between genes (Ayroles et al, 2009). This indicates that inbreeding depression is caused by a few deleterious genes with major effect that, in turn, affect a large proportion of the rest of the genome (Ayroles et al, 2009).…”

“…Recent evidence has shown that a large amount of inbreeding depression is caused by complex epistatic interactions between genes (Ayroles et al, 2009). This indicates that inbreeding depression is caused by a few deleterious genes with major effect that, in turn, affect a large proportion of the rest of the genome (Ayroles et al, 2009). Thus, to dissect the genetic basis of inbreeding depression, it is essential to separate observed molecular responses to inbreeding into causal effects and secondary consequences.…”

Analysis of the effects of inbreeding on lifespan and starvation resistance in Drosophila melanogaster

“…Genes being differentially expressed between inbred and outbred lines have been shown to include an overrepresentation of those associated with metabolism, stress and defense suggesting that inbreeding induces some of the same responses as environmental stress (Kristensen et al 2002;Pedersen et al 2005;Ayroles et al 2009;Paige 2010). It has been suggested that the deleterious effects of inbreeding could, at least to some extent, be ameliorated by a set of genes that respond to inbreeding (Vermeulen et al 2008).…”

“…Both gene expression and metabolite data indicate that fundamental metabolic processes are changed or modified by inbreeding (Kristensen et al , 2006Pedersen et al 2008;Ayroles et al 2009). Whether good quality individuals have higher or lower rate of metabolism is however still an unresolved question (Hawkins and Day 1999;Konarzewski and Diamond 1995;Reinhold 1999;Nilsson 2002;Rantala and Roff 2006;Johnston et al 2007;Ketola and Kotiaho 2009a, b;Mikkelsen et al 2010).…”