Summary of the project

Recent studies have revealed that there are thousands of small non-canonical ORFs that show signatures of translation and produce microproteins (Ruiz-Orera et al., 2018; Mudge et al., 2022). Microproteins are proteins shorter than 100 amino acids, which have remained undetected by gene annotation programs because of their small size. The comparison of the sequences of these ORFs, and the transcripts containing them, across different species have shown that many of them evolutionary young, having emerged de novo from previously non-coding genomic regions. So many of them could be involved species- and lineage-specific adaptations.

The aim of the study will be to obtain a catalogue of microproteins expressed in different mammalian species using ribosome profiling data (Ribo-Seq), and to investigate their properties, including age and expression tissue. Ribo-Seq reads correspond to ribosome-protected RNA fragment that are being translated. We will be using a pipeline already developed in the lab to identify small translated ORFs from Ribo-Seq reads. Ribo-Seq data is available for several tissues (testis, brain, heart, liver) and species, including human, chimpanzee, macaque, mouse, rat, opossum, platypus and chicken.

We will identify microproteins that are only translated in certain tissues and which could have driven tissue-specific adaptations. We will also investigate how well conserved the microproteins are across species using homology searches and available genomic synteny maps. This will provide information on the evolutionary age of the microproteins. We will investigate the properties of microproteins of different age to better understand how they evolve over time. We expect to discover new microproteins that have emerged very recently, for example in the human branch, as well as widely conserved microproteins which have remained unannotated.

The work will take place at the Research Programme on Biomedical Informatics (grib.upf.edu), under the supervision of Mar Albà (group leader of the Evolutionary Genomics group) and Cova Vara (postdoctoral researcher).

References

Ruiz-Orera J, Verdaguer-Grau P, Villanueva-Cañas JL, Messeguer X, Albà MM. Translation of neutrally evolving peptides provides a basis for de novo gene evolution. Nature Ecology and Evolution 2018 May;2(5):890-896.

Mudge JM, Ruiz-Orera J, Prensner JR et al. Standardized annotation of translated open reading frames. Nature Biotechnoly 2022 Jul;40(7):994-999.

Sandmann CL, Schulz JF, Ruiz-Orera J et al. Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames. Mol Cell. 2023 Mar 16;83(6):994-1011.e18.

Skills required

R and Python programming