ALBERT

Description: Birds can be classified into altricial and precocial. The hatchlings of altricial birds are almost naked, whereas those of precocial birds are covered with natal down. This regulatory divergence is thought to reflect environmental adaptation, but the molecular basis of the divergence is unclear. To address this issue, we chose the altricial zebra finch and the precocial chicken as the model animals. We noted that zebra finch hatchlings show natal down growth suppressed anterior dorsal (AD) skin but partially down-covered posterior dorsal (PD) skin. Comparing the transcriptomes of AD and PD skins, we found that the feather growth promoter SHH (sonic hedgehog) was expressed higher in PD skin than in AD skin. Moreover, the data suggested that the FGF (fibroblast growth factor)/Mitogen-activated protein kinase (MAPK) signaling pathway is involved in natal down growth suppression and that FGF16 is a candidate upstream signaling suppressor. Ectopic expression of FGF16 on chicken leg skin showed downregulation of SHH , upregulation of the feather growth suppressor FGF10 , and suppression of feather bud elongation, similar to the phenotype found in zebra finch embryonic AD skin. Therefore, we propose that FGF16 -related signals suppress natal down elongation and cause the naked AD skin in zebra finch. Our study provides insights into the regulatory divergence in natal down formation between precocial and altricial birds.

Description: The cadherin–catenin complex (CCC) mediates cell–cell adhesion in bilaterian animals by linking extracellular cadherin-based adhesions to the actin cytoskeleton. However, it is unknown whether the basic organization of the complex is conserved across all metazoans. We tested whether protein interactions and actin-binding properties of the CCC are conserved in a nonbilaterian animal, the sea anemone Nematostella vectensis . We demonstrated that N. vectensis has a complete repertoire of cadherin–catenin proteins, including two classical cadherins, one α-catenin, and one β-catenin. Using size-exclusion chromatography and multi-angle light scattering, we showed that α-catenin and β-catenin formed a heterodimer that bound N. vectensis Cadherin-1 and -2. Nematostella vectensis α-catenin bound F-actin with equivalent affinity as either a monomer or an α/β-catenin heterodimer, and its affinity for F-actin was, in part, regulated by a novel insert between the N- and C-terminal domains. Nematostella vectensis α-catenin inhibited Arp2/3 complex-mediated nucleation of actin filaments, a regulatory property previously thought to be unique to mammalian αE-catenin. Thus, despite significant differences in sequence, the key interactions of the CCC are conserved between bilaterians and cnidarians, indicating that the core function of the CCC as a link between cell adhesions and the actin cytoskeleton is ancestral in the eumetazoans.

Description: Nucleotide insertions/deletions are ubiquitous in eukaryotic genomes, and the resulting hemizygous (unpaired) DNA has significant, heritable effects on adjacent DNA. However, little is known about the genetic behavior of insertion DNA. Here, we describe a binary transgenic system to study the behavior of insertion DNA during meiosis. Transgenic Arabidopsis lines were generated to carry two different defective reporter genes on nonhomologous chromosomes, designated as "recipient" and "donor" lines. Double hemizygous plants (harboring unpaired DNA) were produced by crossing between the recipient and the donor, and double homozygous lines (harboring paired DNA) via self-pollination. The transfer of the donor’s unmutated sequence to the recipient generated a functional β-glucuronidase gene, which could be visualized by histochemical staining and corroborated by polymerase chain reaction amplification and sequencing. More than 673 million seedlings were screened, and the results showed that meiotic ectopic recombination in the hemizygous lines occurred at a frequency 〉6.49-fold higher than that in the homozygous lines. Gene conversion might have been exclusively or predominantly responsible for the gene correction events. The direct measurement of ectopic recombination events provided evidence that an insertion, in the absence of an allelic counterpart, could scan the entire genome for homologous counterparts with which to pair. Furthermore, the unpaired (hemizygous) architectures could accelerate ectopic recombination between itself and interchromosomal counterparts. We suggest that the ectopic recombination accelerated by hemizygous architectures may be a general mechanism for interchromosomal recombination through ubiquitously dispersed repeat sequences in plants, ultimately contributing to genetic renovation and eukaryotic evolution.

Description: Adaptation of a complex trait often requires the accumulation of many modifications to finely tune its underpinning molecular components to novel environmental requirements. The investigation of cis -acting regulatory modifications can be used to pinpoint molecular systems partaking in such complex adaptations. Here, we identify cis -acting modifications with the help of an interspecific crossing scheme designed to distinguish modifications derived in each of the two sister species, Arabidopsis halleri and A. lyrata . Allele-specific expression levels were assessed in three environmental conditions chosen to reflect interspecific ecological differences: cold exposure, dehydration, and standard conditions. The functions described by Gene Ontology categories enriched in cis -acting mutations are markedly different in A. halleri and A. lyrata , suggesting that polygenic adaptation reshaped distinct polygenic molecular functions in the two species. In the A. halleri lineage, an excess of cis -acting changes affecting metal transport and homeostasis was observed, confirming that the well-known heavy metal tolerance of this species is the result of polygenic selection. In A. lyrata , we find a marked excess of cis -acting changes among genes showing a transcriptional response to cold stress in the outgroup species A. thaliana . The adaptive relevance of these changes will have to be validated. We finally observed that polygenic molecular functions enriched in derived cis -acting changes are more constrained at the amino acid level. Using the distribution of cis -acting variation to tackle the polygenic basis of adaptation thus reveals the contribution of mutations of small effect to Darwinian adaptation.

Description: Phylogenetic networks are a generalization of evolutionary trees that can be used to represent reticulate processes such as hybridization and recombination. Here, we introduce a new approach called TriLoNet (Trinet Level- one Network algorithm) to construct such networks directly from sequence alignments which works by piecing together smaller phylogenetic networks. More specifically, using a bottom up approach similar to Neighbor-Joining, TriLoNet constructs level-1 networks (networks that are somewhat more general than trees) from smaller level-1 networks on three taxa. In simulations, we show that TriLoNet compares well with Lev1athan, a method for reconstructing level-1 networks from three-leaved trees. In particular, in simulations we find that Lev1athan tends to generate networks that overestimate the number of reticulate events as compared with those generated by TriLoNet. We also illustrate TriLoNet’s applicability using simulated and real sequence data involving recombination, demonstrating that it has the potential to reconstruct informative reticulate evolutionary histories. TriLoNet has been implemented in JAVA and is freely available at https://www.uea.ac.uk/computing/TriLoNet .

Description: The growing number of sequenced genomes allows us now to address a key question in genetics and evolutionary biology: which genomic changes underlie particular phenotypic changes between species? Previously, we developed a computational framework called Forward Genomics that associates phenotypic to genomic differences by focusing on phenotypes that are independently lost in different lineages. However, our previous implementation had three main limitations. Here, we present two new Forward Genomics methods that overcome these limitations by (1) directly controlling for phylogenetic relatedness, (2) controlling for differences in evolutionary rates, and (3) computing a statistical significance. We demonstrate on large-scale simulated data and on real data that both new methods substantially improve the sensitivity to detect associations between phenotypic and genomic differences. We applied these new methods to detect genomic differences involved in the loss of vision in the blind mole rat and the cape golden mole, two independent subterranean mammals. Forward Genomics identified several genes that are enriched in functions related to eye development and the perception of light, as well as genes involved in the circadian rhythm. These new Forward Genomics methods represent a significant advance in our ability to discover the genomic basis underlying phenotypic differences between species. Source code: https://github.com/hillerlab/ForwardGenomics/

Description: Phylogenetic trees are pervasively used to depict evolutionary relationships. Increasingly, researchers need to visualize large trees and compare multiple large trees inferred for the same set of taxa (reflecting uncertainty in the tree inference or genuine discordance among the loci analyzed). Existing tree visualization tools are however not well suited to these tasks. In particular, side-by-side comparison of trees can prove challenging beyond a few dozen taxa. Here, we introduce Phylo.io , a web application to visualize and compare phylogenetic trees side-by-side. Its distinctive features are: highlighting of similarities and differences between two trees, automatic identification of the best matching rooting and leaf order, scalability to large trees, high usability, multiplatform support via standard HTML5 implementation, and possibility to store and share visualizations. The tool can be freely accessed at http://phylo.io and can easily be embedded in other web servers. The code for the associated JavaScript library is available at https://github.com/DessimozLab/phylo-io under an MIT open source license.

Description: When viruses spread, outbreaks can be spawned in previously unaffected regions. Depending on the time and mode of introduction, each regional outbreak can have its own epidemic dynamics. The migration and phylodynamic processes are often intertwined and need to be taken into account when analyzing temporally and spatially structured virus data. In this article, we present a fully probabilistic approach for the joint reconstruction of phylodynamic history in structured populations (such as geographic structure) based on a multitype birth–death process. This approach can be used to quantify the spread of a pathogen in a structured population. Changes in epidemic dynamics through time within subpopulations are incorporated through piecewise constant changes in transmission parameters. We analyze a global human influenza H3N2 virus data set from a geographically structured host population to demonstrate how seasonal dynamics can be inferred simultaneously with the phylogeny and migration process. Our results suggest that the main migration path among the northern, tropical, and southern region represented in the sample analyzed here is the one leading from the tropics to the northern region. Furthermore, the time-dependent transmission dynamics between and within two HIV risk groups, heterosexuals and injecting drug users, in the Latvian HIV epidemic are investigated. Our analyses confirm that the Latvian HIV epidemic peaking around 2001 was mainly driven by the injecting drug user risk group.

Description: Ribosomal proteins (r-proteins) are increasingly used as an alternative to ribosomal rRNA for prokaryotic systematics. However, their routine use is difficult because r-proteins are often not or wrongly annotated in complete genome sequences, and there is currently no dedicated exhaustive database of r-proteins. RiboDB aims at fulfilling this gap. This weekly updated comprehensive database allows the fast and easy retrieval of r-protein sequences from publicly available complete prokaryotic genome sequences. The current version of RiboDB contains 90 r-proteins from 3,750 prokaryotic complete genomes encompassing 38 phyla/major classes and 1,759 different species. RiboDB is accessible at http://ribodb.univ-lyon1.fr and through ACNUC interfaces.