Mixture Density Regression reveals frequent recent adaptation in the human genome

How much genome differences between species reflect neutral or adaptive evolution is a central question in evolutionary genomics. In humans and other mammals, the prevalence of adaptive versus neutral genomic evolution has proven particularly difficult to quantify. The difficulty notably stems from the highly heterogenous organization of mammalian genomes at multiple levels (functional sequence density, recombination, etc.) that complicates the interpretation and distinction of adaptive vs. neutral evolution signals. Here, we introduce Mixture Density Regressions (MDRs) for the study of the determinants of recent adaptation in the human genome. MDRs provide a flexible regression model based on multiple Gaussian distributions. We use MDRs to model the association between recent selection signals and multiple genomic factors likely to affect positive selection, if the latter was common enough in the first place to generate these associations. We find that a MDR model with two Gaussian distributions provides an excellent fit to the genome-wide distribution of a common sweep summary statistic (iHS), with one of the two distributions likely capturing the positively selected component of the genome. We further find several factors associated with recent adaptation, including the recombination rate, the density of regulatory elements in immune cells and testis, GC-content, gene expression in immune cells, the density of mammal-wide conserved elements, and the distance to the nearest virus-interacting gene. These results support that strong positive selection was relatively common in recent human evolution and highlight MDRs as a powerful tool to make sense of signals of recent genomic adaptation.

Genomic adaptation in the CAZyome and specialised metabolism of the plant-associated Streptomyces violaceusniger clade

Streptomycetes are Gram-positive actinobacteria largely represented in the plant root microbiota. The genetic determinants involved in the presence of Streptomyces in the rhizosphere are largely unknown and can rely on the ability to degrade plant-derived compounds such as cell-wall polysaccharides and on the production of specialised metabolites. To address whether Streptomyces strains recruited into root microbiota share genomic specificities related to these two functions, we engaged a comparative genomic analysis using a newly sequenced rhizospheric strain, Streptomyces sp. AgN23 and strains from the phylogenetically related S. violaceusniger clade. This analysis enlightens a shared prominent CAZyome potentially involved in plant polysaccharides degradation and a strong conservation of antimicrobials biosynthetic clusters (rustmicin, mediomycin, niphimycin, nigericin) as well as plant bioactive compounds (nigericin, echosides, elaiophylin). Taken together, our work supports the hypothesis that specific hydrolytic enzymes and specialised metabolites repertoires may play important roles in the development of Streptomyces strains in the rhizosphere.

Decreased recent adaptation at human mendelian disease genes as a possible consequence of interference between advantageous and deleterious variants

Advances in genome sequencing have dramatically improved our understanding of the genetic basis of human diseases, and thousands of human genes have been associated with different diseases. Despite our expanding knowledge of gene-disease associations, and despite the medical importance of disease genes, their recent evolution has not been thoroughly studied across diverse human populations. In particular, recent genomic adaptation at disease genes has not been characterized as well as purifying selection and long-term adaptation. Understanding the relationship between disease and adaptation at the gene level in the human genome is hampered by the fact that we don’t know whether disease genes have experienced more, less, or as much adaptation as non-disease genes during the last ~50,000 years of recent human evolution. Here, we compare the rate of strong recent adaptation in the form of selective sweeps between mendelian, non-infectious disease genes and non-disease genes across 26 distinct human populations from the 1,000 Genomes Project. We find that mendelian disease genes have experienced far less selective sweeps compared to non-disease genes especially in Africa. This sweep deficit at mendelian disease genes is less visible in East Asia or Europe. Investigating further the possible causes of the sweep deficit at disease genes, we find that this deficit is very strong at disease genes with both low recombination rates and with high numbers of associated disease variants, but is almost non-existent at disease genes with higher recombination rates or lower numbers of associated disease variants. Because segregating recessive deleterious variants have the ability to interfere with adaptive ones, these observations strongly suggest that adaptation has been slowed down by the presence of interfering recessive deleterious variants at disease genes. This is further supported by population simulations that show that interference at disease genes is expected to be lower in East Asia and Europe. These results clarify the evolutionary relationship between disease genes and recent genomic adaptation, and suggest that disease genes suffer not only from a higher load of segregating deleterious mutations, but also from a transient inability to adapt as much, and/or as fast as the rest of the genome.

Data-driven, participatory characterization of traditional farmer varieties discloses teff (Eragrostis tef) adaptive and breeding potential under current and future climates

In smallholder farming systems, traditional farmer varieties of neglected and underutilized crops species (NUS) support the livelihoods of millions of growers and consumers. NUS combine cultural and agronomic value with local adaptation, and call for transdisciplinary methods to evaluate their breeding potential. Here, we combined farmers' traditional knowledge, genomics, and climate science to characterize 366 Ethiopian teff (Eragrostis tef) farmer varieties and breeding materials. We found that teff genetic diversity in Ethiopia could be organized in six genetic clusters associated to climate variation on the landscape. A participatory evaluation conducted in collaboration with local farmers could consistently identify best performing varieties and inform a genome wide association study to identify candidate genes for farmers' appreciation, phenology, yield, and local adaptation. By modelling the genomic adaptation of teff to current and projected climates, we identified an area around lake Tana where teff cropping will be most vulnerable to climate change. Our results show that transdisciplinary approaches may efficiently propel untapped NUS farmer varieties into modern breeding to foster more resilient and sustainable cropping systems

Bringing Disciplines and People Together to Characterize the Plastic and Genetic Responses of Molluscs to Environmental Change

Molluscs are remarkably diverse and are found across nearly all ecosystems, meaning that members of this ancient animal phylum provide a powerful means to study genomic-phenotype connections in a climate change framework. Recent advances in genomic sequencing technologies and genome assembly approaches finally allow the relatively cheap and tractable assembly of high-quality mollusc genome resources. After a brief review of these issues and advances, we use a case-study approach to provide some concrete examples of phenotypic plasticity and genomic adaptation in molluscs in response to environmental factors expected to be influenced by climate change. Our goal is to use molluscs as a “common currency” to demonstrate how organismal and evolutionary biologists can use natural systems to make phenotype-genotype connections in the context of changing environments. In parallel, we emphasize the critical need to collaborate and integrate findings across taxa and disciplines in order to use new data and information to advance our understanding of mollusc biology in the context of global environmental change. We end with a brief synthetic summary of the papers inspired by the 2021 SICB Symposium “Genomic Perspectives in Comparative Physiology of Molluscs: Integration across Disciplines”.

Effectiveness of experimental and commercial pertussis vaccines in the elimination of Bordetella pertussis isolates with different genetic profiles in murine model

The aim of this study was to compare the elimination of Bordetella pertussis clinical isolates, representing different genotypes in relation to alleles encoding virulence factors (MLST—multi-locus antigen sequence typing), MLVA type (multi-locus variable-number tandem repeat analysis) and PFGE group (pulsed-field gel electrophoresis) from the lungs of naive mice or mice were immunised with the commercial whole-cell pertussis vaccine, the acellular pertussis vaccine and the experimental whole-cell pertussis vaccine. Molecular data indicate that the resurgence of pertussis in populations with high vaccine coverage is associated with genomic adaptation of B. pertussis, to vaccine selection pressure. Pertactin-negative B. pertussis isolates were suspected to contribute to the reduced vaccine effectiveness. It was shown that one of the isolates used is PRN deficient. The mice were intranasally challenged with bacterial suspension containing approximately 5 × 10 7 CFU/ml B. pertussis. The immunogenicity of the tested vaccines against PT (pertussis toxin), PRN (pertactin), FHA (filamentous haemagglutinin) and FIM (fimbriae types 2 and 3) was examined. The commercial whole-cell and acellular pertussis vaccines induced an immunity effective at eliminating the genetically different B. pertussis isolates from the lungs. However, the elimination of the PRN-deficient isolate from the lungs of mice vaccinated with commercial vaccines was delayed as compared to the PRN ( +) isolate, suggesting phenotypic differences with the circulating isolates and vaccine strains. The most effective vaccine was the experimental vaccine with the composition identical to that of the strains used for infection.