Germline ecology: managed herds, tolerated flocks, and pest control.

Multicopy sequences evolve adaptations for increasing their copy number within nuclei. The activities of multicopy sequences under constraints imposed by cellular and organismal selection result in a rich intranuclear ecology in germline cells. mtDNA and rDNA are managed as domestic herds subject to selective breeding by the genes of the single-copy genome. Transposable elements lead a peripatetic existence in which they must continually move to new sites to keep ahead of inactivating mutations at old sites and undergo exponential outbreaks when the production of new copies exceeds the rate of inactivation of old copies. Centromeres become populated by repeats that do little harm. Organisms with late sequestration of germ cells tend to evolve more 'junk' in their genomes than organisms with early sequestration of germ cells.

Rhesus macaque social functioning is paternally, but not maternally, inherited by sons: potential implications for autism.

BACKGROUND: Quantitative autistic traits are common, heritable, and continuously distributed across the general human population. Patterns of autistic traits within families suggest that more complex mechanisms than simple Mendelian inheritance-in particular, parent of origin effects-may be involved. The ideal strategy for ascertaining parent of origin effects is by half-sibling analysis, where half-siblings share one, but not both, parents and each individual belongs to a unique combination of paternal and maternal half-siblings. While this family structure is rare in humans, many of our primate relatives, including rhesus macaques, have promiscuous breeding systems that consistently produce paternal and maternal half-siblings for a given index animal. Rhesus macaques, like humans, also exhibit pronounced variation in social functioning. METHODS: Here we assessed differential paternal versus maternal inheritance of social functioning in male rhesus macaque offspring (N = 407) using ethological observations and ratings on a reverse-translated quantitative autistic trait measurement scale. Restricted Maximum Likelihood mixed models with unbounded variance estimates were used to estimate the variance components needed to calculate the genetic contribution of parents as the proportion of phenotypic variance (σ2P) between sons that could uniquely be attributed to their shared genetics (σ2g), expressed as σ2g/σ2P (or the proportion of phenotypic variance attributable to genetic variance), as well as narrow sense heritability (h2). RESULTS: Genetic contributions and heritability estimates were strong and highly significant for sons who shared a father but weak and non-significant for sons who shared a mother. Importantly, these findings were detected using the same scores from the same sons in the same analysis, confirmed when paternal and maternal half-siblings were analyzed separately, and observed with two methodologically distinct behavioral measures. Finally, genetic contributions were similar for full-siblings versus half-siblings that shared only a father, further supporting a selective paternal inheritance effect. LIMITATIONS: These data are correlational by nature. A larger sample that includes female subjects, enables deeper pedigree assessments, and supports molecular genetic analyses is warranted. CONCLUSIONS: Rhesus macaque social functioning may be paternally, but not maternally, inherited by sons. With continued investigation, this approach may yield important insights into sex differences in autism's genetic liability.

Increased Clinical Signs and Mortality in IFNAR(-/-) Mice Immunised with the Bluetongue Virus Outer-Capsid Proteins VP2 or VP5, after Challenge with an Attenuated Heterologous Serotype.

Bluetongue is an economically important disease of domesticated and wild ruminants caused by bluetongue virus (BTV). There are at least 36 different serotypes of BTV (the identity of which is determined by its outer-capsid protein VP2), most of which are transmitted by Culicoides biting midges. IFNAR(-/-) mice immunised with plant-expressed outer-capsid protein VP2 (rVP2) of BTV serotypes -1, -4 or -8, or the smaller outer-capsid protein rVP5 of BTV-10, or mock-immunised with PBS, were subsequently challenged with virulent strains of BTV-4 or BTV-8, or with an attenuated clone of BTV-1 (BTV-1RGC7). The mice that had received rVP2 generated a protective immune response against the homologous BTV serotype, reducing viraemia (as detected by qRT-PCR), the severity of clinical signs and mortality levels. No cross-serotype protection was observed after challenge with the heterologous BTV serotypes. However, the severity of clinical signs, viraemia and fatality levels after challenge with the attenuated strain of BTV-1 were all increased in mice immunised with rVP2 of BTV-4 and BTV-8, or with rVP5 of BTV10. The possibility is discussed that non-neutralising antibodies, reflecting serological relationships between the outer-capsid proteins of these different BTV serotypes, could lead to 'antibody-dependent enhancement of infection' (ADE). Such interactions could affect the epidemiology and emergence of different BTV strains in the field and would therefore be relevant to the design and implementation of vaccination campaigns.

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.

Paradox lost: Concerted evolution and centromeric instability: Centromeres are hospitable habitats for repeats that evolve adaptations for proliferation within the nucleus sometimes at organismal cost.: Centromeres are hospitable habitats for repeats that evolve adaptations for proliferation within the nucleus sometimes at organismal cost.

Homologous centromeres compete for segregation to the secondary oocyte nucleus at female meiosis I. Centromeric repeats also compete with each other to populate centromeres in mitotic cells of the germline and have become adapted to use the recombinational machinery present at centromeres to promote their own propagation. Repeats are not needed at centromeres, rather centromeres appear to be hospitable habitats for the colonization and proliferation of repeats. This is probably an indirect consequence of two distinctive features of centromeric DNA. Centromeres are subject to breakage by the mechanical forces exerted by microtubules and meiotic crossing-over is suppressed. Centromeric proteins acting in trans are under selection to mitigate the costs of centromeric repeats acting in cis. Collateral costs of mitotic competition at centromeres may help to explain the high rates of aneuploidy observed in early human embryos.

After short interbirth intervals, captive callitrichine monkeys have higher infant mortality.

Life history theory predicts a trade-off between the quantity and quality of offspring. Short interbirth intervals-the time between successive births-may increase the quantity of offspring but harm offspring quality. In contrast, long interbirth intervals may bolster offspring quality while reducing overall reproductive output. Further research is needed to determine whether this relationship holds among primates, which have intensive parental investment. Using Cox proportional hazards models, we examined the effects of interbirth intervals (short, normal, or long) on infant survivorship using a large demographic dataset (n = 15,852) of captive callitrichine monkeys (marmosets, tamarins, and lion tamarins). In seven of the nine species studied, infants born after short interbirth intervals had significantly higher risks of mortality than infants born after longer interbirth intervals. These results suggest that reproduction in callitrichine primates may be limited by physiologic constraints, such that short birth spacing drives higher infant mortality.

Concerted evolution of ribosomal DNA: Somatic peace amid germinal strife: Intranuclear and cellular selection maintain the quality of rRNA.

Most eukaryotes possess many copies of rDNA. Organismal selection alone cannot maintain rRNA function because the effects of mutations in one rDNA are diluted by the presence of many other rDNAs. rRNA quality is maintained by processes that increase homogeneity of rRNA within, and heterogeneity among, germ cells thereby increasing the effectiveness of cellular selection on ribosomal function. A successful rDNA repeat will possess adaptations for spreading within tandem arrays by intranuclear selection. These adaptations reside in the non-coding regions of rDNA. Single-copy genes are predicted to manage processes of intranuclear and cellular selection in the germline to maintain the quality of rRNA expressed in somatic cells of future generations.

A Textual Deconstruction of the RNA World.

RNAs can do many things. They can store information, act in the world, and respond to the world. Because of these capabilities biologists have proposed a primordial 'RNA world' in which RNA, rather than DNA, performed the central role of replicator and repository of adaptive information. Deacon dismisses this hypothesis because replication is not about anything and because the structure of replicating molecules cannot contain information about the environment. I dispute both claims. An RNA and its opposite-sense complement represent each other and, by two rounds of complementation, represent themselves. Although (with some exceptions) nucleic acid sequences do not change in response to their present environment, these sequences embody information about ancestral environments via the selective filtering of alternative sequences in those environments. Nucleic acid sequences are the textual record of what has worked in the past.

Serological Cross-Reactions between Expressed VP2 Proteins from Different Bluetongue Virus Serotypes.

Bluetongue (BT) is a severe and economically important disease of ruminants that is widely distributed around the world, caused by the bluetongue virus (BTV). More than 28 different BTV serotypes have been identified in serum neutralisation tests (SNT), which, along with geographic variants (topotypes) within each serotype, reflect differences in BTV outer-capsid protein VP2. VP2 is the primary target for neutralising antibodies, although the basis for cross-reactions and serological variations between and within BTV serotypes is poorly understood. Recombinant BTV VP2 proteins (rVP2) were expressed in Nicotiana benthamiana, based on sequence data for isolates of thirteen BTV serotypes (primarily from Europe), including three 'novel' serotypes (BTV-25, -26 and -27) and alternative topotypes of four serotypes. Cross-reactions within and between these viruses were explored using rabbit anti-rVP2 sera and post BTV-infection sheep reference-antisera, in I-ELISA (with rVP2 target antigens) and SNT (with reference strains of BTV-1 to -24, -26 and -27). Strong reactions were generally detected with homologous rVP2 proteins or virus strains/serotypes. The sheep antisera were largely serotype-specific in SNT, but more cross-reactive by ELISA. Rabbit antisera were more cross-reactive in SNT, and showed widespread, high titre cross-reactions against homologous and heterologous rVP2 proteins in ELISA. Results were analysed and visualised by antigenic cartography, showing closer relationships in some, but not all cases, between VP2 topotypes within the same serotype, and between serotypes belonging to the same 'VP2 nucleotype'.

Analysis of immune responses to attenuated alcelaphine herpesvirus 1 formulated with and without adjuvant.

The experimental vaccine for bovine malignant catarrhal fever consists of viable attenuated alcelaphine herpesvirus 1 (AlHV-1) derived by extensive culture passage, combined with an oil-in-water adjuvant, delivered intramuscularly. This immunisation strategy was over 80% effective in previous experimental and field trials and protection appeared to be associated with induction of virus-neutralising antibodies. Whether the vaccine virus is required to be viable at the point of immunisation and whether adjuvant is required to induce the appropriate immune responses remains unclear. To address these issues two studies were performed, firstly to analyse immune responses in the presence and absence of adjuvant and secondly, to investigate immune responses to vaccines containing adjuvant plus viable or inactivated AlHV-1. The first study showed that viable attenuated AlHV-1 in the absence of adjuvant induced virus-specific antibodies but the titres of virus-neutralising antibodies were significantly lower than those induced by vaccine containing viable virus and adjuvant, suggesting adjuvant was required for optimal responses. In contrast, the second study found that the vaccine containing inactivated (>99.9%) AlHV-1 induced similar levels of virus-neutralising antibody to the equivalent formulation containing viable AlHV-1. Together these studies suggest that the MCF vaccine acts as an antigen depot for induction of immune responses, requiring adjuvant and a suitable antigen source, which need not be viable virus. These observations may help in directing the development of alternative MCF vaccine formulations for distribution in the absence of an extensive cold chain.

Microstructures amplify carotenoid plumage signals in tanagers.

Brilliantly-colored birds are a model system for research into evolution and sexual selection. Red, orange, and yellow carotenoid-colored plumages have been considered honest signals of condition; however, sex differences in feather pigments and microstructures are not well understood. Here, we show that microstructures, rather than carotenoid pigments, seem to be a major driver of male-female color differences in the social, sexually-dimorphic tanager genus Ramphocelus. We comprehensively quantified feather (i) color (using spectrophotometry), (ii) pigments (using liquid chromatography-mass spectrometry (LC-MS)), and (iii) microstructures (using scanning electron microscopy (SEM) and finite-difference time-domain (FDTD) optical modeling). Males have significantly more saturated color patches than females. However, our exploratory analysis of pigments suggested that males and females have concordant carotenoid pigment profiles across all species (MCMCglmm model, female:male ratio = 0.95). Male, but not female, feathers have elaborate microstructures which amplify color appearance. Oblong, expanded feather barbs in males enhance color saturation (for the same amount of pigment) by increasing the transmission of optical power through the feather. Dihedral barbules (vertically-angled, strap-shaped barbules) in males reduce total reflectance to generate "super black" and "velvet red" plumage. Melanin in females explains some, but not all, of the male-female plumage differences. Our results suggest that a widely cited index of honesty, carotenoid pigments, cannot fully explain male appearance. We propose that males are selected to evolve amplifiers-in this case, microstructures that enhance appearance-that are not necessarily themselves linked to quality.

A host-independent role for Fasciola hepatica transforming growth factor-like molecule in parasite development.

The trematode parasite Fasciola hepatica causes chronic infection in hosts, enabled by an immunosuppressed environment. Both host and parasite factors are known to contribute to this suggesting that avoidance of immunopathology is beneficial to both parties. We have previously characterised a parasite transforming growth factor (TGF)-like molecule, FhTLM, that interacts with host macrophages to prevent antibody-dependent cell cytotoxicity (ADCC). FhTLM is one of many described helminth TGF homologues and multiple helminths are now known to utilise host immune responses as developmental cues. To test whether, or how, F. hepatica uses FhTLM to manipulate host immunity, we initially examined its effects on the CD4 T-cell phenotype. Despite inducing IL-10, there was no induction of FoxP3 within the CD4 T-cell compartment. In addition to inducing IL-10, a wide range of chemokines were elicited from both CD4 T-cells and macrophages. However, no growth or survival advantage was conferred on F. hepatica in our co-culture system when CD4 T-cells, macrophages, or eosinophils were tested. Finally, using RNA interference we were able to verify a host-independent role for FhTLM in parasite growth. Despite the similarities of FhTLM with other described helminth TGF homologues, here we demonstrate species-specific divergence.

The Evolution of Imprinted microRNAs and Their RNA Targets.

Mammalian genomes contain many imprinted microRNAs. When an imprinted miRNA targets an unimprinted mRNA their interaction may have different fitness consequences for the loci encoding the miRNA and mRNA. In one possible outcome, the mRNA sequence evolves to evade regulation by the miRNA by a simple change of target sequence. Such a response is unavailable if the targeted sequence is strongly constrained by other functions. In these cases, the mRNA evolves to accommodate regulation by the imprinted miRNA. These evolutionary dynamics are illustrated using the examples of the imprinted C19MC cluster of miRNAs in primates and C2MC cluster in mice that are paternally expressed in placentas. The 3' UTR of PTEN, a gene with growth-related and metabolic functions, appears to be an important target of miRNAs from both clusters.

On the logic of Fisherian sexual selection.

In Fisher's model of sexual selection, a female preference for a male trait spreads together with the trait because their genetic bases become correlated. This can be interpreted as a "greenbeard" system: a preference gene, by inducing a female to mate with a trait-bearing male, favors itself because the male is disproportionately likely also to carry the preference gene. Here, we use this logic to argue that Fisherian sexual selection in diploids proceeds via two channels: (i) trait-bearing males are disproportionately the product of matings between preference-bearing mothers and trait-bearing fathers, and thus trait and preference genes are correlated "in trans"; (ii) trait and preference genes come into gametic phase disequilibrium, and thus are correlated "in cis." Gametic phase disequilibrium is generated by three distinct mechanisms that we identify. The trans channel does not operate when sexual selection is restricted to the haploid phase, and therefore represents a fundamental difference between haploid and diploid models of sexual selection. We show that the cis and trans channels contribute equally to the spread of the preference when recombination between the preference and trait loci is free, but that the trans channel is substantially more important when linkage is tight.

Embryo Selection and Mate Choice: Can 'Honest Signals' Be Trusted?

When a measure becomes a target, it often ceases to be a good measure - an effect familiar from the declining usefulness of standardized testing in schools. This economic principle also applies to mate choice and, perhaps surprisingly, pregnancy. Just as females screen potential mates under many metrics, human mothers unconsciously screen embryos for quality. 'Examinees' are under intense selection to improve test performance by exaggerating formerly 'honest' signals of quality. Examiners must change their screening criteria to maintain useful information (but cannot abandon old criteria unilaterally). By the resulting 'proxy treadmill', new honest indicators arise while old degraded indicators linger, resulting in trait elaboration and exaggeration. Hormone signals during pregnancy show extreme evolutionary escalation (akin to elaborate mating displays).

Retrotransposon gag-like 1 (RTL1) and the molecular evolution of self-targeting imprinted microRNAs.

BACKGROUND: Transcription of the antisense strand of RTL1 produces a sense mRNA that is targeted for degradation by antisense microRNAs transcribed from the sense strand. Translation of the mRNA produces a retrotransposon-derived protein that is implicated in placental development. The sense and antisense transcripts are oppositely imprinted: sense mRNAs are expressed from the paternally-derived chromosome, antisense microRNAs from the maternally-derived chromosome. RESULTS: Two microRNAs at the RTL1 locus, miR-431 and the rodent-specific miR-434, are derived from within tandem repeats. We present an evolutionary model for the establishment of a new self-targeting microRNA derived from within a tandem repeat that inhibits production of RTL1 protein when maternally-derived in heterozygotes but not when paternally-derived. CONCLUSIONS: The interaction of sense and antisense transcripts can be interpreted as a form of communication between maternally-derived and paternally-derived RTL1 alleles that possesses many of the features of a greenbeard effect. This interaction is evolutionary stable, unlike a typical greenbeard effect, because of the necessary complementarity between microRNAs and mRNA transcribed from opposite strands of the same double helix. We conjecture that microRNAs and mRNA cooperate to reduce demands on mothers when an allele is paired with itself in homozygous offspring. REVIEWERS: This article was reviewed by Eugene Berezikov and Bernard Crespi.

A comparative study of litter size and sex composition in a large dataset of callitrichine monkeys.

In many birds and mammals, the size and sex composition of litters can have important downstream effects for individual offspring. Primates are model organisms for questions of cooperation and conflict, but the factors shaping interactions among same-age siblings have been less-studied in primates because most species bear single young. However, callitrichines (marmosets, tamarins, and lion tamarins) frequently bear litters of two or more, thereby providing the opportunity to ask whether variation in the size and sex composition of litters affects development, survival, and reproduction. To investigate these questions, we compiled a large dataset of nine species of callitrichines (n = 27,080 individuals; Callithrix geoffroyi, Callithrix jacchus, Cebuella pygmaea, Saguinus imperator, Saguinus oedipus, Leontopithecus chrysomelas, Leontopithecus chrysopygus, Leontopithecus rosalia, and Callimico goeldii) from zoo and laboratory populations spanning 80 years (1938-2018). Through this comparative approach, we found several lines of evidence that litter size and sex composition may impact fitness. Singletons have higher survivorship than litter-born peers and they significantly outperform litter-born individuals on two measures of reproductive performance. Further, for some species, individuals born in a mixed-sex litter outperform isosexually-born individuals (i.e., those born in all-male or all-female litters), suggesting that same-sex competition may limit reproductive performance. We also document several interesting demographic trends. All but one species (C. pygmaea) has a male-biased birth sex ratio with higher survivorship from birth to sexual maturity among females (although this was significant in only two species). Isosexual litters occurred at the expected frequency (with one exception: C. pygmaea), unlike other animals, where isosexual litters are typically overrepresented. Taken together, our results indicate a modest negative effect of same-age sibling competition on reproductive output in captive callitrichines. This study also serves to illustrate the value of zoo and laboratory records for biological inquiry.

Cooperation and conflict in human pregnancy.

For many humans living today, obstetric care begins early in pregnancy, and most babies are born in hospitals. These are precautionary measures. Medical complications during the brief nine months of pregnancy are such a common part of human experience that we rarely ask ourselves why gestation does not always proceed as smoothly and reliably as the lifelong beating of our heart or filtration of blood by our kidneys. The birth of a healthy child is central to reproductive fitness and must have been subject to strong natural selection. Why then should placentas be less reliable organs than hearts or kidneys? Why should maternal hearts and kidneys be more subject to catastrophic failures during pregnancy than at other times? A crucial contrast distinguishes obstetrics from cardiology and nephrology. The coordinated activities of heart and kidneys take place within an individual comprised of genetically largely identical cells, whereas pregnancy involves an interaction between genetically-distinct individuals whose cooperation is obviated by evolutionary conflicts of interest.