When and why are mitochondria paternally inherited?

In contrast with nuclear genes that are passed on through both parents, mitochondrial genes are maternally inherited in most species, most of the time. The genetic conflict stemming from this transmission asymmetry is well-documented, and there is an abundance of population-genetic theory associated with it. While occasional or aberrant paternal inheritance occurs, there are only a few cases where exclusive paternal inheritance of mitochondrial genomes is the evolved state. Why this is remains poorly understood. By examining commonalities between species with exclusive paternal inheritance, we discuss what they may tell us about the evolutionary forces influencing mitochondrial inheritance patterns. We end by discussing recent technological advances that make exploring the causes and consequences of paternal inheritance feasible.

Adaptation in the face of internal conflict: the paradox of the organism revisited.

The paradox of the organism refers to the observation that organisms appear to function as coherent purposeful entities, despite the potential for within-organismal components like selfish genetic elements and cancer cells to erode them from within. While it is commonly accepted that organisms may pursue fitness maximisation and can be thought to hold particular agendas, there is a growing recognition that genes and cells do so as well. This can lead to evolutionary conflicts between an organism and the parts that reside within it. Here, we revisit the paradox of the organism. We first outline its conception and relationship to debates about adaptation in evolutionary biology. Second, we review the ways selfish elements may exploit organisms, and the extent to which this threatens organismal integrity. To this end, we introduce a novel classification scheme that distinguishes between selfish elements that seek to distort transmission versus those that seek to distort phenotypic traits. Our classification scheme also highlights how some selfish elements elude a multi-level selection decomposition using the Price equation. Third, we discuss how the organism can retain its status as the primary fitness-maximising agent in the face of selfish elements. The success of selfish elements is often constrained by their strategy and further limited by a combination of fitness alignment and enforcement mechanisms controlled by the organism. Finally, we argue for the need for quantitative measures of both internal conflicts and organismality.

Spatial cumulant models enable spatially informed treatment strategies and analysis of local interactions in cancer systems.

Theoretical and applied cancer studies that use individual-based models (IBMs) have been limited by the lack of a mathematical formulation that enables rigorous analysis of these models. However, spatial cumulant models (SCMs), which have arisen from theoretical ecology, describe population dynamics generated by a specific family of IBMs, namely spatio-temporal point processes (STPPs). SCMs are spatially resolved population models formulated by a system of differential equations that approximate the dynamics of two STPP-generated summary statistics: first-order spatial cumulants (densities), and second-order spatial cumulants (spatial covariances). We exemplify how SCMs can be used in mathematical oncology by modelling theoretical cancer cell populations comprising interacting growth factor-producing and non-producing cells. To formulate model equations, we use computational tools that enable the generation of STPPs, SCMs and mean-field population models (MFPMs) from user-defined model descriptions (Cornell et al. Nat Commun 10:4716, 2019). To calculate and compare STPP, SCM and MFPM-generated summary statistics, we develop an application-agnostic computational pipeline. Our results demonstrate that SCMs can capture STPP-generated population density dynamics, even when MFPMs fail to do so. From both MFPM and SCM equations, we derive treatment-induced death rates required to achieve non-growing cell populations. When testing these treatment strategies in STPP-generated cell populations, our results demonstrate that SCM-informed strategies outperform MFPM-informed strategies in terms of inhibiting population growths. We thus demonstrate that SCMs provide a new framework in which to study cell-cell interactions, and can be used to describe and perturb STPP-generated cell population dynamics. We, therefore, argue that SCMs can be used to increase IBMs' applicability in cancer research.

Genetic conflicts and the case for licensed anthropomorphizing.

The use of intentional language in biology is controversial. It has been commonly applied by researchers in behavioral ecology, who have not shied away from employing agential thinking or even anthropomorphisms, but has been rarer among researchers from more mechanistic corners of the discipline, such as population genetics. One research area where these traditions come into contact-and occasionally clash-is the study of genetic conflicts, and its history offers a good window to the debate over the use of intentional language in biology. We review this debate, paying particular attention to how this interaction has played out in work on genomic imprinting and sex chromosomes. In light of this, we advocate for a synthesis of the two approaches, a form of licensed anthropomorphizing. Here, agential thinking's creative potential and its ability to identify the fulcrum of evolutionary pressure are combined with the rigidity of formal mathematical modeling.

Meiosis solved the problem of gerrymandering.

Gerrymandering, the structuring of voting districts to favour certain politicians and political groups, undermines fair elections and presents a serious challenge to democracy. We introduce a solution to gerrymandering inspired by the biological process of cell division in sexually reproducing organisms, meiosis, in which the boundaries of electorates are frequently redrawn by randomizing algorithms. By demonstrating the deep parallels between meiosis and John Rawls's concept of a 'veil of ignorance', we also show how one of the biggest threats to the integrity of meiosis-selfish genetic elements, genes that promote their own transmission at the expense of organismal fitness-can inspire another potential advantage to frequent random redistricting.

Sewall Wright's criticism of the gene's-eye view of evolution.

The gene's-eye view of evolution has played a central but contentious role in evolutionary biology for the past half-century. By envisioning evolutionary history as a struggle between competing selfish genes, it accelerated the shift from organism-centric to gene-centric explanations that began with the emergence population genetics a century ago. At the forefront of this shift were George C. Williams and Richard Dawkins, who advocated an approach to thinking about evolution first introduced by R. A. Fisher. In this Perspective, I discuss the criticism of the gene's-eye view developed by another architect of population genetics, Sewall Wright, whose "On genic and organismic selection" was published in Evolution in 1980. I start by outlining the history of the gene's-eye view and then show how some long-standing differences in opinion over its value can be traced back to disagreements between Fisher and Wright, especially over Fisher's concept of genetic variance and the importance of epistasis. I end with some reflections on the role of genes and organisms in evolutionary explanations.

Mitochondrial-Y chromosome epistasis in Drosophila melanogaster.

The coordination between mitochondrial and nuclear genes is crucial to eukaryotic organisms. Predicting the nature of these epistatic interactions can be difficult because of the transmission asymmetry of the genes involved. While autosomes and X-linked genes are transmitted through both sexes, genes on the Y chromosome and in the mitochondrial genome are uniparentally transmitted through males and females, respectively. Here, we generate 36 otherwise isogenic Drosophila melanogaster strains differing only in the geographical origin of their mitochondrial genome and Y chromosome, to experimentally examine the effects of the uniparentally inherited parts of the genome, as well as their interaction, in males. We assay longevity and gene expression through RNA-sequencing. We detect an important role for both mitochondrial and Y-linked genes, as well as extensive mitochondrial-Y chromosome epistasis. In particular, genes involved in male reproduction appear to be especially sensitive to such interactions, and variation on the Y chromosome is associated with differences in longevity. Despite these interactions, we find no evidence that the mitochondrial genome and Y chromosome are co-adapted within a geographical region. Overall, our study demonstrates a key role for the uniparentally inherited parts of the genome for male biology, but also that mito-nuclear interactions are complex and not easily predicted from simple transmission asymmetries.

Enforcement is central to the evolution of cooperation.

Cooperation occurs at all levels of life, from genomes, complex cells and multicellular organisms to societies and mutualisms between species. A major question for evolutionary biology is what these diverse systems have in common. Here, we review the full breadth of cooperative systems and find that they frequently rely on enforcement mechanisms that suppress selfish behaviour. We discuss many examples, including the suppression of transposable elements, uniparental inheritance of mitochondria and plastids, anti-cancer mechanisms, reciprocation and punishment in humans and other vertebrates, policing in eusocial insects and partner choice in mutualisms between species. To address a lack of accompanying theory, we develop a series of evolutionary models that show that the enforcement of cooperation is widely predicted. We argue that enforcement is an underappreciated, and often critical, ingredient for cooperation across all scales of biological organization.

Coevolution of Genome Architecture and Social Behavior.

Although social behavior can have a strong genetic component, it can also result in selection on genome structure and function, thereby influencing the evolution of the genome itself. Here we explore the bidirectional links between social behavior and genome architecture by considering variation in social and/or mating behavior among populations (social polymorphisms) and across closely related species. We propose that social behavior can influence genome architecture via associated demographic changes due to social living. We establish guidelines to exploit emerging whole-genome sequences using analytical approaches that examine genome structure and function at different levels (regulatory vs structural variation) from the perspective of both molecular biology and population genetics in an ecological context.

Sexual conflict through mother's curse and father's curse.

In contrast with autosomes, lineages of sex chromosomes reside for different amounts of time in males and females, and this transmission asymmetry makes them hotspots for sexual conflict. Similarly, the maternal inheritance of the mitochondrial genome (mtDNA) means that mutations that are beneficial in females can spread in a population even if they are deleterious in males, a form of sexual conflict known as Mother's Curse. While both Mother's Curse and sex chromosome induced sexual conflict have been well studied on their own, the interaction between mitochondrial genes and genes on sex chromosomes is poorly understood. Here, we use analytical models and computer simulations to perform a comprehensive examination of how transmission asymmetries of nuclear, mitochondrial, and sex chromosome-linked genes may both cause and resolve sexual conflicts. For example, the accumulation of male-biased Mother's Curse mtDNA mutations will lead to selection in males for compensatory nuclear modifier loci that alleviate the effect. We show how the Y chromosome, being strictly paternally transmitted provides a particularly safe harbor for such modifiers. This analytical framework also allows us to discover a novel kind of sexual conflict, by which Y chromosome-autosome epistasis may result in the spread of male beneficial but female deleterious mutations in a population. We christen this phenomenon Father's Curse. Extending this analytical framework to ZW sex chromosome systems, where males are the heterogametic sex, we also show how W-autosome epistasis can lead to a novel kind of nuclear Mother's Curse. Overall, this study provides a comprehensive framework to understand how genetic transmission asymmetries may both cause and resolve sexual conflicts.

The effect of camelina sativa oil and fish intakes on fatty acid compositions of blood lipid fractions.

BACKGROUND AND AIMS: Blood lipid fractions serve as objective biomarkers of dietary fat intake. It is unclear which fatty acid pool most accurately reflects the dietary intakes of different n-3 PUFAs. We aimed to investigate the effect of fish and camelina sativa oil (CSO) intakes on fatty acid composition of erythrocyte membranes (EM), plasma phospholipids (PL), cholesteryl esters (CE) and triglycerides (TG). We also aimed to identify the most appropriate blood lipid fraction for assessing n-3 PUFA intake. METHODS AND RESULTS: Altogether 79 volunteers with impaired glucose metabolism were randomly assigned either to CSO, fatty fish, lean fish or control groups for 12 weeks. Fatty acid compositions of lipid pools were measured by gas chromatography. The proportion of alpha-linolenic acid (ALA) increased in all lipid pools in the CSO group (false discovery rate (FDR) p < 0.001 for all). Similarly, the proportions of EPA and DHA increased in all lipid fractions in the fatty fish group (FDR p < 0.001 for EM, PL and CE; FDR p = 0.005 for TG; FDR p < 0.001 for EM, PL, CE; FDR p < 0.007 for TG, respectively). Changes in the dietary intakes of ALA, EPA and DHA correlated with the changes in their proportions in all lipid pools (r = 0.3-0.5, p < 0.05). CONCLUSION: There is no difference in the ability of blood lipid fractions in reflecting the dietary intake of different n-3 PUFAs over a time period of 12 weeks in subjects with high baseline omega-3 index. This trial was registered in Clinicaltrials.gov (NCT01768429).

Selfish genetic elements.

Selfish genetic elements (historically also referred to as selfish genes, ultra-selfish genes, selfish DNA, parasitic DNA, genomic outlaws) are genetic segments that can enhance their own transmission at the expense of other genes in the genome, even if this has no or a negative effect on organismal fitness. [1-6] Genomes have traditionally been viewed as cohesive units, with genes acting together to improve the fitness of the organism. However, when genes have some control over their own transmission, the rules can change, and so just like all social groups, genomes are vulnerable to selfish behaviour by their parts. Early observations of selfish genetic elements were made almost a century ago, but the topic did not get widespread attention until several decades later. Inspired by the gene-centred views of evolution popularized by George Williams[7] and Richard Dawkins,[8] two papers were published back-to-back in Nature in 1980-by Leslie Orgel and Francis Crick[9] and Ford Doolittle and Carmen Sapienza[10] respectively-introducing the concept of selfish genetic elements (at the time called "selfish DNA") to the wider scientific community. Both papers emphasized that genes can spread in a population regardless of their effect on organismal fitness as long as they have a transmission advantage. Selfish genetic elements have now been described in most groups of organisms, and they demonstrate a remarkable diversity in the ways by which they promote their own transmission.[11] Though long dismissed as genetic curiosities, with little relevance for evolution, they are now recognized to affect a wide swath of biological processes, ranging from genome size and architecture to speciation.[12].

Alterations in fatty acid metabolism in response to obesity surgery combined with dietary counseling.

BACKGROUND: The effects of obesity surgery on serum and adipose tissue fatty acid (FA) profile and FA metabolism may modify the risk of obesity-related diseases. METHODS: We measured serum (n=122) and adipose tissue (n=24) FA composition and adipose tissue mRNA expression of genes regulating FA metabolism (n=100) in participants of the Kuopio Obesity Surgery Study (KOBS, age 47.2±8.7 years, BMI 44.6±6.0, 40 men, 82 women) before and one year after obesity surgery. As part of the surgery protocol, all the subjects were instructed to add sources of unsaturated fatty acids, such as rapeseed oil and fatty fish, into their diet. The results were compared with changes in serum FA composition in 122 subjects from the Finnish Diabetes Prevention study (DPS) (age 54.3±7.1 years, BMI 32.2±4.6, 28 men, 94 women). RESULTS: The proportion of saturated FAs decreased and the proportion of n-3 and n-6 FAs increased in serum triglycerides after obesity surgery (all P<0.002). Weight loss predicted changes in quantitative amounts of saturated FAs, monounsaturated FAs, n-3 and n-6 FAs in triglycerides (P<0.002 for all). Moreover, the changes in adipose tissue FAs reflected the changes in serum FAs, and some of the changes were associated with mRNA expression of elongases and desaturases in adipose tissue (all P<0.05). In line with this the estimated activity of elongase (18:1 n-7/16:1 n-7) increased significantly after obesity surgery in all lipid fractions (all P<4 × 10-7) and the increase in the estimated activity of D5D in triglycerides was associated with higher weight loss (r=0.415, P<2 × 10-6). Changes in serum FA profile were similar after obesity surgery and lifestyle intervention, except for the change in the absolute amounts of n-3 FAs between the two studies (P=0.044). CONCLUSIONS: Beneficial changes in serum and adipose tissue FAs after obesity surgery could be associated with changes in endogenous metabolism and diet.

Confirmation of a Campylobacteriosis Outbreak Associated with Chicken Liver Pâté Using PFGE and WGS.

In May 2012, an outbreak of campylobacteriosis occurred in southern Sweden at a wedding reception affecting 44 persons. A total of 17 cases were notified (13 were culture positive for Campylobacter spp.). Epidemiological investigation suspected chicken liver pâté as the source of infection. The liver pâté had been deliberately undercooked, lightly fried to keep the right texture and mixed with spices. Campylobacter isolates from six cases as well as three Campylobacter isolates from chicken flocks previously raised by the producer delivering the liver were subtyped using pulsed-field gel electrophoresis and whole-genome sequencing. Indistinguishable PFGE profiles were identified among five human and one chicken C. jejuni isolates as well among the two C. coli isolates, one from a human case and one from a chicken. WGS supported the PFGE findings; the six C. jejuni isolates belonged to one cluster. All these six isolates were of MLST type ST 50 (ST-CC 21). This study highlights the importance of a combination of strict biosecurity at the flock-level as well as adequate cooking of chicken liver to prevent transmission of Campylobacter to humans.

Plasma polyunsaturated fatty acids are directly associated with cognition in overweight children but not in normal weight children.

AIM: Polyunsaturated fatty acids are essential nutrients for the normal development of the brain. We investigated the associations between plasma polyunsaturated fatty acids and cognition in normal weight and overweight children. METHODS: The study recruited 386 normal weight children and 58 overweight children aged six to eight years and blood samples were drawn after a 12-hour fast. We assessed plasma polyunsaturated fatty acids using gas chromatography, cognition using Raven's Coloured Progressive Matrices, and overweight and obesity using the age-specific and sex-specific cut-offs from the International Obesity Task Force. The data were analysed by linear regression analyses adjusted for age and sex. RESULTS: Higher proportions of eicosapentaenoic acid in plasma triacylglycerols (ß = 0.311, p = 0.020, p = 0.029 for interaction) and docosahexaenoic acid in plasma triacylglycerols (ß = 0.281, p = 0.038, p = 0.049 for interaction) were both associated with higher Raven's scores in overweight children but not in normal weight children. Higher eicosapentaenoic acid to arachidonic acid ratios in triacylglycerols (ß = 0.317, p = 0.019) and phospholipids (ß = 0.273, p = 0.046) were directly associated with the Raven's score in overweight children but not in normal weight children. CONCLUSION: These findings suggest that increasing the consumption of fish and other sources of eicosapentaenoic acid and docosahexaenoic acid may improve cognition among overweight children.

Transposable element evolution in the allotetraploid Capsella bursa-pastoris.

PREMISE OF THE STUDY: Shifts in ploidy affect the evolutionary dynamics of genomes in a myriad of ways. Population genetic theory predicts that transposable element (TE) proliferation may follow because the genomewide efficacy of selection should be reduced and the increase in gene copies may mask the deleterious effects of TE insertions. Moreover, in allopolyploids, TEs may further accumulate because of hybrid breakdown of TE silencing. However, to date the evidence of TE proliferation following an increase in ploidy is mixed, and the relative importance of relaxed selection vs. silencing breakdown remains unclear. METHODS: We used high-coverage whole-genome sequence data to evaluate the abundance, genomic distribution, and population frequencies of TEs in the self-fertilizing recent allotetraploid Capsella bursa-pastoris (Brassicaceae). We then compared the C. bursa-pastoris TE profile with that of its two parental diploid species, outcrossing C. grandiflora and self-fertilizing C. orientalis. KEY RESULTS: We found no evidence that C. bursa-pastoris has experienced a large genomewide proliferation of TEs relative to its parental species. However, when centromeric regions are excluded, we found evidence of significantly higher abundance of retrotransposons in C. bursa-pastoris along the gene-rich chromosome arms compared with C. grandiflora and C. orientalis. CONCLUSIONS: The lack of a genomewide effect of allopolyploidy on TE abundance, combined with the increases TE abundance in gene-rich regions, suggests that relaxed selection rather than hybrid breakdown of host silencing explains the TE accumulation in C. bursa-pastoris.

Selfish genetic elements and the gene's-eye view of evolution.

During the last few decades, we have seen an explosion in the influx of details about the biology of selfish genetic elements. Ever since the early days of the field, the gene's-eye view of Richard Dawkins, George Williams, and others, has been instrumental to make sense of new empirical observations and to the generation of new hypotheses. However, the close association between selfish genetic elements and the gene's-eye view has not been without critics and several other conceptual frameworks have been suggested. In particular, proponents of multilevel selection models have used selfish genetic elements to criticize the gene's-eye view. In this paper, I first trace the intertwined histories of the study of selfish genetic elements and the gene's-eye view and then discuss how their association holds up when compared with other proposed frameworks. Next, using examples from transposable elements and the major transitions, I argue that different models highlight separate aspects of the evolution of selfish genetic elements and that the productive way forward is to maintain a plurality of perspectives. Finally, I discuss how the empirical study of selfish genetic elements has implications for other conceptual issues associated with the gene's-eye view, such as agential thinking, adaptationism, and the role of fitness maximizing models in evolution.

Association of plasma fatty acid composition with plasma irisin levels in normal weight and overweight/obese children.

BACKGROUND: Irisin has been suggested to protect against overweight. There are no previous data on the association of plasma fatty acid (FA) composition with plasma irisin. OBJECTIVES: We studied the association of FA composition with plasma irisin in normal weight and overweight/obese children. METHODS: This cross-sectional study included pre-pubertal children (388 normal weight children and 55 overweight/obese children); 6-9 years of age, taking part in the Physical Activity and Nutrition in Children Study. After an overnight fast, we measured plasma FA composition by gas chromatography and plasma irisin levels by enzyme-linked immunosorbent assay. RESULTS: Higher proportion of total monounsaturated fatty acids in plasma cholesteryl esters (CEs) (ß = 0.139, P = 0.003) and phospholipids (PLs) (ß = 0.147, P = 0.002) and lower proportion of total polyunsaturated fatty acids in plasma CE (ß = -0.130, P = 0.006) and PL (ß = -0.165, P < 0.001) were associated with higher plasma irisin level in the whole study group. The association of plasma FA composition with plasma irisin level was stronger among overweight/obese children compared to normal weight children. Higher proportion of γ-linolenic acid (ß = 0.324, P = 0.017) and lower proportion of linoleic acid (ß = -0.397, P = 0.005) in plasma CE were related to higher plasma irisin level among overweight/obese children, indicating the direct association of estimated D6D activity in plasma CE (ß = 0.343, P = 0.011) with plasma irisin. Furthermore, higher proportion of oleic acid in plasma CE (ß = 0.345, P = 0.012) and PL (ß = 0.292, P = 0.033) and higher proportion of adrenic acid (ß = 0.366, P = 0.008) and docosapentaenoic acid (ß = 0.351, P = 0.010) in plasma PL were associated with higher plasma irisin level among overweight/obese children. CONCLUSION: Metabolically unfavourable plasma FA profile was associated with higher plasma irisin level especially in overweight/obese children, suggesting that excess body fat might modulate these relationships.