Biology subjects

Johnson, A. D.

Publications and source records attributed to Johnson, A. D..

21 records · Page 2Linked to original sources

bioRxiv2018

Intrinsic cooperativity potentiates parallel cis-regulatory evolution

Convergent evolutionary events in independent lineages provide an opportunity to understand why evolution favors certain outcomes over others. We studied such a case, where a large set of genes--those coding for the ribosomal proteins--gained cis-regulatory sequences for a particular transcription regulator (Mcm1) in independent fungal lineages. We present evidence that these gains occurred because Mcm1 shares a mechanism of transcriptional activation with an ancestral regulator of the ribosomal protein genes, Rap1. Specifically, we show that Mcm1 and Rap1 have the inherent ability to cooperatively activate transcription through contacts with the general transcription factor TFIID. Because the two regulatory proteins share a common interaction partner, the presence of one ancestral cis-regulatory sequence can \"channel\" random mutations into functional sites for the second regulator. At a genomic scale, this type of intrinsic cooperativity can account for a pattern of parallel evolution involving the fixation of hundreds of substitutions.

evolutionary biology↗

bioRxiv2017

Virtual Genome Walking: Generating gene models for the salamander Ambystoma mexicanum

Large repeat rich genomes present challenges for assembly and identification of gene models with short read technologies. Here we present a method we call Virtual Genome Walking which uses an iterative assembly approach to first identify exons from de-novo assembled transcripts and assemble whole genome reads against each exon. This process is iterated allowing the extension of exons. These linked assemblies are refined to generate gene models including upstream and downstream genomic sequence as well as intronic sequence. We test this method using a 20X genomic read set for the axolotl, the genome of which is estimated to be 30 Gb in size. These reads were previously reported to be effectively impossible to assemble. Here we provide almost 1 Gb of assembled sequence describing over 19,000 gene models for the axolotl. Gene models stop assembling either due to localised low coverage in the genomic reads, or the presence of repeats. We validate our observations by comparison with previously published axolotl bacterial artificial chromosome (BAC) sequences. In addition we analysed axolotl intron length, intron-exon structure, repeat content and synteny. These gene-models, sequences and annotations are freely available for download from https://tinyurl.com/y8gydc6n. The software pipeline including a docker image is available from https://github.com/LooseLab/iterassemble. These methods will increase the value of low coverage sequencing of understudied model systems.

bioinformatics↗

bioRxiv2017

Genome-wide Association Study Of Plasma Proteins Identifies Putatively Causal Genes, Proteins, And Pathways For Cardiovascular Disease

Identifying genetic variants associated with circulating protein concentrations (pQTLs) and integrating them with variants from genome-wide association studies (GWAS) may illuminate the proteomes causal role in disease and bridge a GWAS knowledge gap for hitherto unexplained SNP-disease associations. We conducted GWAS of 71 high-value proteins for cardiovascular disease in 6,861 Framingham Heart Study participants followed by external replication. We comprehensively mapped thousands of pQTLs, including functional annotations and clinical-trait associations, and created an integrated plasma-protein-QTL searchable database. We next identified 15 proteins with pQTLs coinciding with coronary heart disease (CHD)-related variants from GWAS or tested causal for CHD by Mendelian randomization; most of these proteins were associated with new-onset cardiovascular disease events in Framingham participants with long-term follow-up. Identifying pQTLs and integrating them with GWAS results yields insights into genes, proteins, and pathways that may be causally associated with disease and can serve as therapeutic targets for treatment and prevention.

epidemiology↗