Conflicting and ambiguous names of overlapping ORFs in the SARS-CoV-2 genome: A homology-based resolution.

At least six small alternative-frame open reading frames (ORFs) overlapping well-characterized SARS-CoV-2 genes have been hypothesized to encode accessory proteins. Researchers have used different names for the same ORF or the same name for different ORFs, resulting in erroneous homological and functional inferences. We propose standard names for these ORFs and their shorter isoforms, developed in consultation with the Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. We recommend calling the 39 codon Spike-overlapping ORF ORF2b; the 41, 57, and 22 codon ORF3a-overlapping ORFs ORF3c, ORF3d, and ORF3b; the 33 codon ORF3d isoform ORF3d-2; and the 97 and 73 codon Nucleocapsid-overlapping ORFs ORF9b and ORF9c. Finally, we document conflicting usage of the name ORF3b in 32 studies, and consequent erroneous inferences, stressing the importance of reserving identical names for homologs. We recommend that authors referring to these ORFs provide lengths and coordinates to minimize ambiguity caused by prior usage of alternative names

DDRprot: a database of DNA damage response-related proteins

The DNA Damage Response (DDR) signalling network is an essential system that protects the genome’s integrity. The DDRprot database presented here is a resource that integrates manually curated information on the human DDR network and its sub-pathways. For each particular DDR protein, we present detailed information about its function. If involved in post-translational modifications (PTMs) with each other, we depict the position of the modified residue/s in the three-dimensional structures, when resolved structures are available for the proteins. All this information is linked to the original publication from where it was obtained. Phylogenetic information is also shown, including time of emergence and conservation across 47 selected species, family trees and sequence alignments of homologues. The DDRprot database can be queried by different criteria: pathways, species, evolutionary age or involvement in (PTM). Sequence searches using hidden Markov models can be also used.E.A.-L. was supported by the European Commission grant [FP7-REGPOT-2012-2013-1; A.A. was partially supported by the Spanish Ministry of Science and Innovation grant [PS09/02111].Peer reviewe

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Investigating trade-offs in sexual populations with gene flow

Understanding the processes underlying trade-offs between environments, where adaptation to one results in decreased fitness in another, is important in understanding evolutionary processes across a wide range of organisms. The molecular basis of this evolutionary phenomenon is a key question in biology generally. Unravelling the basis of trade-offs has application in understanding the maintenance of sexual reproduction in most eukaryotic lineages in spite of apparent costs. In this chapter, we discuss the evolutionary problem of sexual reproduction, and its relationship with trade-offs, working from August Weismann’s suggestion that sex improves the efficiency of natural selection. We argue that microbial experimental evolution is an important way in which claims about trade-offs and sex can be tested and that these experiments need to be developed to better represent real world ecological and evolutionary problems. We review experiments, including from our laboratory, which bear on the question of the benefits of sex in complex environments. We also argue for the necessity of a genomic rather than merely genetic perspective on these questions

Differentially regulated genes under different growth conditions.

<p>(A) Example of a transcriptionally and translationally upregulated gene in LB compared to BHI control. The novel gene XECs170 is highlighted in pink. The transcription of XECs170 is increased 2.7-fold and translation 9.8-fold. (B) Summary of differentially regulated genes in LB compared to BHI control. For all three gene categories, downregulation dominates. (C) Example of a transcriptionally and translationally downregulated gene in BHI COS compared to BHI control. Transcription of XECs197 is 5.5-fold and translation is 129-fold reduced at the stress condition. (D) Summary of differentially regulated genes in BHI COS compared to BHI control. Downregulation at the translational level clearly dominates for all gene categories.</p

Three novel genes with RIBOseq signals as examples.

<p>In the lower part, the corresponding section of the genome is shown with the novel gene highlighted in pink. In the upper part, the strand-specifically mapped RIBOseq reads are displayed, whereby each black line represents a sequenced read.</p