Hybrid speciation driven by multilocus introgression of ecological traits

Hybridization allows adaptations to be shared among lineages and may trigger the evolution of new species1,2. However, convincing examples of homoploid hybrid speciation remain rare because it is challenging to demonstrate that hybridization was crucial in generating reproductive isolation3. Here we combine population genomic analysis with quantitative trait locus mapping of species-specific traits to examine a case of hybrid speciation in Heliconius butterflies. We show that Heliconius elevatus is a hybrid species that is sympatric with both parents and has persisted as an independently evolving lineage for at least 180,000 years. This is despite pervasive and ongoing gene flow with one parent, Heliconius pardalinus, which homogenizes 99% of their genomes. The remaining 1% introgressed from the other parent, Heliconius melpomene, and is scattered widely across the H. elevatus genome in islands of divergence from H. pardalinus. These islands contain multiple traits that are under disruptive selection, including colour pattern, wing shape, host plant preference, sex pheromones and mate choice. Collectively, these traits place H. elevatus on its own adaptive peak and permit coexistence with both parents. Our results show that speciation was driven by introgression of ecological traits, and that speciation with gene flow is possible with a multilocus genetic architecture

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Development of auditory sensitivity in the inferior colliculus of the tammar wallaby (Macropus eugenii)

The Australian tammar wallaby, a macropod marsupial, is now the subject of established investigations into the development of the visual and somatosensory systems (e.g., Waite et al., 1991, 1994; Mark and Marotte, 1992). Recently, we have commenced studies of the development of the auditory system. The particular advantage of the marsupial preparation is that much of its development occurs both slowly and ex utero, the young being carried and suckled in a pouch, so that access is available at very early stages of development. We have now established the timetable for the first appearance and the properties of the scalp-recorded, auditory brainstem response (ABR) in developing wallabies, in several cases monitoring the ABR in longitudinal studies (Cone-Wesson, Hill and Liu, in prep.). Following its first appearance as a simple biphasic wave, in a preparation at around 120 days of pouch life, the ABR progressively becomes more complex, with an increased number of distinct peaks, as the animal matures. A likely reason for the elaboration of the ABR with development is the progressive onset of function in auditory brainstem nuclei, which are candidates as generators of discrete evoked potentials that may sum in the form of the ABR. The present study is concerned with the development of function in the prominent auditory centre, the inferior colliculus (IC). In marsupials, this major midbrain structure receives afferent connections from the more-peripheral auditory nuclei (Aitkin, 1986). The development of the IC has been studied in several mammalian species, rat (Altman and Bayer, 1981), cat (Aitkin and Reynolds, 1975; Moore, 1980), bat (M#x00F6;ller et al., 1978) and rhesus monkey (Cooper and Rakic, 1981), however, little information is available on development of the IC in marsupials (Aitkin et al., 1995)

Oxidation of peptidyl 3,4-Dihydroxyphenylalanine analogues: Implications for the biosynthesis of tunichromes and related oligopeptides

The o-diphenolic amino acid l-3,4-dihydroxyphenylalanine (dopa), the enamine α, β-dehydro-3,4-dihydroxyphenylalanine (Δ-dopa), and/or hydroxylated derivatives thereof, are integrated into the primary sequence of many scleroproteins and polyphenolic oligopeptides such as the celenamides, tunichromes, and halocyamines. After oxidation of N-acetyldopa ethyl ester, a low mol wt analogue of peptidyl dopa, the resultant o-quinone tautomerized to (Z)-α, β-dehydro-3,4-dihydroxyphenylalanine ethyl ester. We have characterized this Δ-dopa derivative and an acetate 1,4-addition product formed during the synthesis. Tautomerization of peptidyl dopa quinone to A-dopa may be involved in the biosynthesis of A-dopa-containing oligopeptides

Pain, frailty and comorbidity on older men: the CHAMP study.

Intrusive pain is likely to have a serious impact on older people with limited ability to respond to additional stressors. Frailty is conceptualised as a functional and biological pattern of decline accumulating across multiple physiological systems, resulting in a decreased capacity to respond to additional stressors. We explored the relationship between intrusive pain, frailty and comorbid burden in 1705 community-dwelling men aged 70 or more who participated in the baseline phase of the CHAMP study, a large epidemiological study of healthy ageing based in Sydney, Australia. 9.4% of men in the study were frail (according to the commonly-used Cardiovascular Health Study frailty criteria).Using a combination of self-report and clinical measures, we found an association between frailty and intrusive pain that remained after accounting for demographic characteristics, number of comorbidities, self-reported depressed mood and arthritis (adjusted odds ratio 1.7 (95% confidence interval (CI) 1.1-2.7), p=0.0149). The finding that adjusting for depressed mood, but not a history of arthritis, attenuated the relationship between frailty and intrusive pain points to a key role for central mechanisms. Additionally, men with the highest overall health burden (frail plus high comorbid burden) were most likely to report intrusive pain (adjusted odds ratio 3.0 (95% CI 1.6-5.5), p=0.0004). These findings provide support for the concept that intrusive pain is an important challenge for older men with limited capacity to respond to additional physical stressors. To our knowledge, this is the first study to explore specifically the relationship between pain and frailty