Complex life exists only with a continuous and rich supply of energy from oxidative phosphorylation in mitochondria. The biochemical machinery that enables the majority of energy production in eukaryotes is encoded by both mitochondrial and nuclear genes so the products of these genomes must interact closely to achieve coordinated function of core respiratory processes. It follows that selection for efficient respiration will lead to selection on optimal combinations of mitochondrial and nuclear genotypes, facilitating mitonuclear coadaptation. In this essay, we outline the modes by which mitochondrial and nuclear genomes coevolve within natural populations, and discuss the implications of mitonuclear coadaptation for diverse fields of study in the biological sciences. We identify six themes in the study of mitonuclear interactions, developed through decades of research, which provide a roadmap for both ecological and biomedical studies seeking to elucidate the contribution of intergenomic coevolution to the genetics of natural populations.

Yellow, orange, and red coloration is a fundamental aspect of avian diversity and serves as an important signal in mate choice and aggressive interactions. This coloration is often produced through the deposition of diet-derived carotenoid pigments, yet the mechanisms of carotenoid uptake and transport are not wellunderstood. The white recessive breed of the common canary (Serinus canaria), which carries an autosomal recessive mutation that renders its plumage pure white, provides a unique opportunity to investigate mechanisms of carotenoid coloration. We carried out detailed genomic and biochemical analyses comparing the white recessive with yellow and red breeds of canaries. Biochemical analysis revealed that carotenoids are absent or at very low concentrations in feathers and several tissues of white recessive canaries, consistent with a genetic defect in carotenoid uptake. Using a combination of genetic mapping approaches, we show that the white recessive allele is due to a splice donor site mutation in the scavenger receptor B1 (SCARB1; also known as SR-B1) gene. This mutation results in abnormal splicing, with the most abundant transcript lacking exon 4. Through functional assays, we further demonstrate that wild-type SCARB1 promotes cellular uptake of carotenoids but that this function is lost in the predominant mutant isoform in white recessive canaries. Our results indicate that SCARB1 is an essential mediator of the expression of carotenoid-based coloration in birds, and suggest a potential link between visual displays and lipid metabolism.coloration | carotenoids | lipid metabolism | Serinus canaria T he yellow, orange, and red coloration of the feathers, skin, and beaks of birds is most commonly produced through the deposition of carotenoid pigments (1). Carotenoid coloration of birds has been a focus of study in the fields of behavior, evolution, and physiology because it plays a key role in mate assessment in many species. In addition, it is frequently an indicator of individual quality, and can signal species identity (2-4). Birds cannot synthesize carotenoids de novo and must acquire them through their diet (1), potentially linking coloration to the acquisition of pigments from the environment (3). Thus, key hypotheses related to honest signaling and sexual selection have been shaped by and are currently being tested in carotenoidornament systems (5, 6). Ultimately, the information content and evolutionary trajectories of carotenoid ornaments are a function of the physiological mechanisms underlying color expression, yet our understanding of these mechanisms is limited.The expression of carotenoid coloration in birds involves four distinct physiological steps: uptake in the gut, transport in circulatory and lymphatic systems, metabolism either at the site of deposition or in the liver, and deposition in the integument (7). Recent progress has been made in understanding how carotenoids are metabolized to novel forms. In 2016, two studies independently identified a key carotenoid metabolism enzyme,...

The rate of hybridization among taxa is a central consideration in any discussion of speciation, but rates of hybridization are difficult to estimate in most wild populations of animals. We used a successful citizen science dataset, eBird, to estimate the rates of hybridization for wild birds in the United States. We calculated the frequency at which hybrid individuals belonging to different species, families, and orders of birds were observed. Between 1 January 2010 and 31 December 2018, a total of 334,770,194 species records were reported to eBird within the United States. Of this total, 212,875 or 0.064% were reported as hybrids. This estimate is higher than the rate of hybridization (0.00167%) reported by Mayr based on impressions from a career studying museum specimens. However, if the 10 most influential hybrid species are removed from the eBird dataset, the rate of hybridization decreases substantially to about 0.009%. We conclude that the rate of hybridization for individuals in most bird species is extremely low, even though the potential for birds to produce fertile offspring through hybrid crosses is high. These findings indicate that there is strong prezygotic selection working in most avian species.

Carotenoid coloration is widely recognized as a signal of individual condition in various animals, but despite decades of study, the mechanisms that link carotenoid coloration to condition remain unresolved. Most birds with red feathers convert yellow dietary carotenoids to red carotenoids in an oxidation process requiring the gene encoding the putative cytochrome P450 enzyme CYP2J19. Here, we tested the hypothesis that the process of carotenoid oxidation and feather pigmentation is functionally linked to mitochondrial performance. Consistent with this hypothesis, we observed high levels of red ketolated carotenoids associated with the hepatic mitochondria of moulting wild house finches ( Haemorhous mexicanus ), and upon fractionation, we found the highest concentration of ketolated carotenoids in the inner mitochondrial membrane. We further found that the redness of growing feathers was positively related to the performance of liver mitochondria. Structural modelling of CYP2J19 supports a direct role of this protein in carotenoid ketolation that may be functionally linked to cellular respiration. These observations suggest that feather coloration serves as a signal of core functionality through inexorable links to cellular respiration in the mitochondria.

The mitonuclear compatibility species concept defines a species as a population that is genetically isolated from other populations by uniquely coadapted mitochondrial (mt) and nuclear genes. A key prediction of this hypothesis is that the mt genotype of each species will be functionally distinct and that introgression of mt genomes will be prevented by mitonuclear incompatibilities that arise when heterospecific mt and nuclear genes attempt to cofunction to enable aerobic respiration. It has been proposed, therefore, that the observation of rampant introgression of mt genotypes from one species to another constitutes a strong refutation of the mitonuclear speciation. The displacement of a mt genotype from a nuclear background with which it co-evolved to a foreign nuclear background will necessarily lead to fitness loss due to mitonuclear incompatibilities. Here I consider two potential benefits of mt introgression between species that may, in some cases, overcome fitness losses arising from mitonuclear incompatibilities. First, the introgressed mt genotype may be better adapted to the local environment than the native mt genotype such that higher fitness is achieved through improved adaptation via introgression. Second, if the mitochondria of the recipient taxa carry a high mutational load, then introgression of a foreign, less corrupt mt genome may enable the recipient taxa to escape its mutational load and gain a fitness advantage. Under both scenarios, fitness gains from novel mt genotypes could theoretically compensate for the fitness that is lost via mitonuclear incompatibility. I also consider the role of endosymbionts in non-adaptive rampant introgression of mt genomes. I conclude that rampant introgression is not necessarily evidence against the idea of tight mitonuclear coadaptation or the mitonuclear compatibility species concept. Rampant mt introgression will typically lead to erasure of species but in some cases could lead to hybrid speciation.