University of Cambridge > > Theory - Chemistry Research Interest Group > DE NOVO PROTEINS: MYTH OR MYSTERY?


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Organisms differ remarkably in their protein and gene content. Even in newly sequenced genomes for which high quality assemblies from closely related organisms exist, between 10 and 30% of all predicted protein coding genes seem to be new because they lack detectable similarity to any other species. Several case studies demonstrated that these enigmatic orphan genes can contribute to lineage-specific adaptation and are often essential for speciation—but how do they arise in first place?

While some genetic mechanisms, such as creation of new ORFs, frame shifts and exonic exaptations can be well supported by comparative genomic analysis, a particularly puzzling paraoxon still awaits solution: from a biophysical perspective, novel proteins should not fold, therefore not be functional and, accordingly, be immediately eliminated from the genome for their toxicity or their energetic burden at the least.

We try to resolve this issue by using population data and cross-species genome comparisons from sticklebacks and insects. We decipher the genetic origins of de-novo proteins and infer their possible adaptive benefits for development, ecological adaptation and speciation. We currently establish computational and experimental techniques to study the biophysical properties of de novo proteins, reconstruct their likely originating sequences and thus “catch them in the act” of emergence.

This talk is part of the Theory - Chemistry Research Interest Group series.

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