ALBERT

Description: The mechanistic basis of regulatory variation and the prevailing evolutionary forces shaping that variation are known to differ between sexes and between chromosomes. Regulatory variation of gene expression can be due to functional changes within a gene itself ( cis ) or in other genes elsewhere in the genome ( trans ). The evolutionary properties of cis mutations are expected to differ from mutations affecting gene expression in trans . We analyze allele-specific expression across a set of X substitution lines in intact adult Drosophila simulans to evaluate whether regulatory variation differs for cis and trans , for males and females, and for X-linked and autosomal genes. Regulatory variation is common (56% of genes), and patterns of variation within D. simulans are consistent with previous observations in Drosophila that there is more cis than trans variation within species (47% vs. 25%, respectively). The relationship between sex-bias and sex-limited variation is remarkably consistent across sexes. However, there are differences between cis and trans effects: cis variants show evidence of purifying selection in the sex toward which expression is biased, while trans variants do not. For female-biased genes, the X is depleted for trans variation in a manner consistent with a female-dominated selection regime on the X. Surprisingly, there is no evidence for depletion of trans variation for male-biased genes on X. This is evidence for regulatory feminization of the X, trans -acting factors controlling male-biased genes are more likely to be found on the autosomes than those controlling female-biased genes.

Description: We explore the evolutionary origins of dosage compensation (DC) in sex chromosomes in the context of metabolic control theory. We consider first the cost of gene loss (hemizygosity) per se in reducing flux, and examine two relationships between flux and fitness (linear and Gaussian) to calculate a fitness cost of hemizygosity. Recognizing that new sex chromosomes are derived from autosomes, we also calculate the cost of unmasking deleterious mutations segregating on the nascent sex chromosomes as loci become hemizygous. The importance of deleterious mutations to the fitness cost of hemizygosity depends on their frequency, and on the relative costs of halving gene dose for wild-type alleles. We then consider the evolution of DC in response to gene loss, and include a cost of overexpression (i.e., DC such that expression exceeds the wild-type homozygote). Even with costs to excess flux, hypomorphic mutations can cause the optimal level of DC to be higher than 2-fold when the absolute cost of hemizygosity is small. Finally, we propose a three-step model of DC evolution: 1) once recombination ceases and the Y begins to deteriorate, genes from longer metabolic pathways should be lost first, as halving these genes does not drastically reduce flux or, thereby, fitness; 2) both the cost of hemizygosity and the presence of hypomorphic mutations will drive an increase in expression, that is, DC; 3) existing DC will now permit loss of genes in short pathways.