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Jungreis, I.

Publications and source records attributed to Jungreis, I..

3 recordsLinked to original sources

Elucidation of Codon Usage Signatures across the Domains of Life

Due to the degeneracy of the genetic code, multiple codons are translated into the same amino acid. Despite being synonymous, these codons are not equally used. Selective pressures are thought to drive the choice among synonymous codons within a genome, while GC content, which is generally attributed to mutational drift, is the major determinant of interspecies codon usage bias. Here we find that in addition to the bias caused by GC content, inter-species codon usage signatures can also be detected. More specifically, we show that a single amino acid, arginine, is the major contributor to codon usage bias differences across domains of life. We then exploit this finding, and show that the identified domain-specific codon bias signatures can be used to classify a given sequence into its corresponding domain with high accuracy. Considering that species belonging to the same domain share similar tRNA decoding strategies, we then wondered whether the inclusion of codon autocorrelation patterns might improve the classification performance of our algorithm. However, we find that autocorrelation patterns are not domain-specific, and surprisingly, are unrelated to tRNA reusage, in contrast to the common belief. Instead, our results reveal that codon autocorrelation patterns are a consequence of codon optimality throughout a sequence, where highly expressed genes display autocorrelated optimal codons, whereas lowly expressed genes display autocorrelated non-optimal codons.

evolutionary biology

Evidence for secondary-variant genetic burden and non-random distribution across biological modules in a recessive ciliopathy

The influence of genetic background on driver mutations is well established; however, the mechanisms by which the background interacts with Mendelian loci remains unclear. We performed a systematic secondary-variant burden analysis of two independent Bardet-Biedl syndrome (BBS) cohorts with known recessive biallelic pathogenic mutations in one of 17 BBS genes for each individual. We observed a significant enrichment of trans-acting rare nonsynonymous secondary variants compared to either population controls or to a cohort of individuals with a non-BBS diagnosis and recessive variants in the same gene set. Strikingly, we found a significant over-representation of secondary alleles in chaperonin-encoding genes, a finding corroborated by the observation of epistatic interactions involving this complex in vivo. These data indicate a complex genetic architecture for BBS that informs the biological properties of disease modules and presents a model paradigm for secondary-variant burden analysis in recessive disorders.

genetics

Nearly all new protein-coding predictions in the CHESS database are not protein-coding

In a 2018 paper posted to bioRxiv, Pertea et al. presented the CHESS database, a new catalog of human gene annotations that includes 1,178 new protein-coding predictions. These are based on evidence of transcription in human tissues and homology to earlier annotations in human and other mammals. Here, we reanalyze the evidence used by CHESS, and find that nearly all protein-coding predictions are false positives. We find that 86% overlap transposons marked by RepeatMasker that are known to frequently result in false positive protein-coding predictions. More than half are homologous to only nine Alu-derived primate sequences corresponding to an erroneous and previously withdrawn Pfam protein domain. The entire set shows poor evolutionary conservation and PhyloCSF protein-coding evolutionary signatures indistinguishable from noncoding RNAs, indicating lack of protein-coding constraint. Only four predictions are supported by mass spectrometry evidence, and even those matches are inconclusive. Overall, the new protein-coding predictions are unsupported by any credible experimental or evolutionary evidence of function, result primarily from homology to genes incorrectly classified as protein-coding, and are unlikely to encode functional proteins.

genomics