Mar Albà Research Group

We have investigated de novo gene evolution in baker’s yeast by comparing the transcriptomes of 11 different yeast species and using ribosome profiling data to identify putatively translated ORFs. The results have now been published in Nature Communications, you can read the paper here:
Uncovering de novo gene birth in yeast using deep transcriptomics.

We have also written a Behind the Paper post in Nature Research Ecology and Evolution Community: Identifying recently evolved genes in yeast.
You can also read a comment about this article at Faculty Opinions.

A great collaboration between different labs at the PRBB!

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A new issue in Experimental Cell Research is dedicated to different aspects of an extensive group of proteins known as micropeptides, many of which still remain hidden in genomes. These peptides are translated from open reading frames shorter than 100 amino acids that are present in transcripts that are currently annotated as non-coding or in the 5′UTR of protein-coding genes. We have written a short piece about our favorite subject, how small ORFs in lncRNAs can evolve into new functional proteins.

You can read it all here: The hidden world of non-canonical ORFs

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Our new paper “Translation of neutrally evolving peptides provides a basis for de novo gene evolution” has been published in Nature Ecology and Evolution on March 19 2018.

During the course of evolution, some genes are gained and others are lost. A well-established mechanism for the emergence of new genes is gene duplication. However, there is increasing evidence that some genes have not originated by gene duplication but de novo from previously non-coding regions of the genome. 

The two processes can be distinguished using sequence comparisons of closely related species. In gene duplication, the new gene retains sequence similarity to the other gene copy. In contrast, genes evolved de novo show no sequence similarity to other genes. In both cases, new genes initially appear by accident. A fraction of these genes will turn out to be beneficial and be subsequently maintained by natural selection.

My interest in new genes started more than fifteen years ago. At that time, I was building a database of herpesvirus protein families at University College London. When I tried to cluster the proteins into families, some would just not cluster. These proteins had unique sequences, they did not resemble any other viral or host protein, yet they performed essential functions. Improbable as it seemed, they had to have originated from DNA sequences other than genes.

Back in Barcelona I teamed up with Jose Castresana to study gene evolution in mammals. In a paper published in 2005 we described many human and mouse proteins that lacked homologues in non-mammalian species. Following the current thinking at the time we proposed that many of them could have been generated by very rapid evolution after gene duplication. However, we also argued that it was possible that some of them had evolved de novo. The reason was that the coding sequences of the young genes were unusually small and this is something one expects for randomly occurring open reading frames but not for functional gene duplicates. Then, Macarena Toll-Riera joined the lab as a PhD student and we decided to revisit this question. With more genomes at hand, the hypothesis of de novo gene birth gained strength. The results were published in 2009 in a paper entitled Origin of primate orphan genes: a comparative genomics approach.

Things became exciting again when Nicholas Ingolia and co-workers reported, in 2011, widespread translation of the mouse transcriptome, including many transcripts previously believed to be non-coding. Jorge Ruiz-Orera, a new PhD in the lab, examined ribosome profiling data from different species and found clear support for the pervasive translation of the transcriptome.

In the present study we have found that an important fraction of the translated peptides show no evolutionary conservation and evolve under no constraints. These peptides can be “tested” for new functions and eventually become new functional proteins, providing a basis for de novo gene evolution. More details of this study can be found here and in the Nature Ecology and Evolution community blog.

Mar Albà

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The Youth Mobile (YoMo) festival is organized by GSMA Mobile World Congress to promote STEAM areas (Science, Technology, Engineering, Art and Mathematics) among young people. The different Centers of the PRBB could be found in the stand BioJuniors. Several members from our group were there on March 1st; they explained how automatic classification algorithms can distinguish between different dog breeds.

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When one thinks about hibernation images of grizzly bears waking up after a long period of inaction come to mind. However, this is a more common physiological adaptation than usually thought, and many mammals hibernate, including diverse species of rats, bats, squirrels and hedgehogs. Some years ago, hibernation was also discovered in lemurs, the closest group to humans known to hibernate. The type of lemurs that hibernate are fat-tailed dwarf lemurs, which use this adaptation to endure the dry season in Madagascar.

Just before hibernation, in the so called fattening period, dwarf lemurs accumulate fat in their tails, which become very thick. This is the fuel that will allow them to survive during the several months they will spent buried in holes.

We wanted to know more about the molecular changes that took place during hibernation in lemurs. Sheena Faherty and collaborators from Duke University visited Madagascar and collected small amounts of fat tissue from the tails of the lemurs, before, during and after the hibernation period. We reconstructed the complete transcriptome from the RNA in the samples and investigated changes in gene expression during hibernation. We could detect a switch from fat storage to fat degradation, as well as inhibition of mitochondrial functions and increased protection against oxidative stress. Until recently, we knew very little about dwarf lemurs at the molecular level. Challenging as this project was, it was a joy to dive into a complete new world.

Mar Albà

The results of this study have been published in Faherty SL*, Villanueva-Cañas JL*, Blanco MB, Albà MM, Yoder AD. Transcriptomics in the wild: Hibernation physiology in free-ranging dwarf lemurs. Molecular Ecology, 29 January 2018.
link to Article

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