Negative frequency dependent selection contributes to the maintenance of a global polymorphism in mitochondrial DNA

Abstract

Background: Understanding the forces that maintain diversity across a range of scales is at the very heart of biology. Frequency-dependent processes are generally recognized as the most central process for the maintenance of ecological diversity. The same is, however, not generally true for genetic diversity. Negative frequency dependent selection, where rare genotypes have an advantage, is often regarded as a relatively weak force in maintaining genetic variation in life history traits because recombination disassociates alleles across many genes. Yet, many regions of the genome show low rates of recombination and genetic variation in such regions (i.e., supergenes) may in theory be upheld by frequency dependent selection.

Results: We studied what is essentially a ubiquitous life history supergene (i.e., mitochondrial DNA) in the fruit fly Drosophila subobscura, showing sympatric polymorphism with two main mtDNA genotypes co-occurring in populations world-wide. Using an experimental evolution approach involving manipulations of genotype starting frequencies, we show that negative frequency dependent selection indeed acts to maintain genetic variation in this region. Moreover, the strength of selection was affected by food resource conditions.

Conclusions: Our work provides novel experimental support for the view that balancing selection through negative frequency dependency acts to maintain genetic variation in life history genes. We suggest that the emergence of negative frequency dependent selection on mtDNA is symptomatic of the fundamental link between ecological processes related to resource use and the maintenance of genetic variation.

Keywords: Balancing selection; Mitochondria; Negative frequency dependent selection; Polymorphism; mtDNA.

Fig. 1

Mitochondrial DNA variation within natural populations of D. subobscura is heavily dominated by the two haplotype groups HI (blue) and HII (red) in all three disjunct parts of its global distribution (white). Apart from populations on the Canary Islands, where other haplotypes (green) are common, the mtDNA haplotype frequencies are similar across populations, with on average 37% of all individuals carrying HI and 58% HII haplotypes. This observation alone suggests that balancing selection is contributing to the maintenance of genetic variation in mtDNA. Several experimental studies have shown that flies carrying HI and HII differ in key life history traits, such as as metabolic rate, development time, adult longevity and desiccation resistance. Distribution map reproduced with permission from Rodríguez-Trelles et al. [42]

Fig. 2

Replicated lines of D. subobscura were founded with flies carrying either mtDNA haplotype HI or HII in different proportions. This figure shows the mean frequency (±SE) of haplotype HI within lines during the course of experimental evolution. Haplotype I increased in frequency when rare and decreased in frequency when common, providing evidence for overall negative frequency dependent selection (red: homogenous resource environment; blue: heterogeneous resource environment)

Fig. 3

(a) Per generation changes in the frequency of HI during 10 generations of experimental evolution, when HI was started as being either the more common or the rarer haplotype. (b) The estimated strength of frequency dependent selection (S_I) on mtDNA haplotypes over 10 generations, where positive values correspond to negative frequency dependency. Selection on mtDNA haplotypes was overall negatively frequency dependent, although those lines where HI was initially rare and that simultaneously experienced a more heterogeneous resource environment showed little evidence of selection. Given here are mean values (±SE) across lines (red: homogenous environment; blue: heterogeneous environment)