De Novo Evolution: New Proteins From Scratch

The journal article "De novo emergence of adaptive membrane proteins from thymine-rich genomic sequences" by Vakirlis et al. (2020) explores a fascinating concept in evolution: the birth of entirely new protein-coding genes from previously non-coding DNA. This research challenges the traditional neo-Darwinian view where genes arise solely through mutations in existing (exon) ones.

The study focuses on budding yeast, a well-studied organism. Recent discoveries suggest that snippets of RNA, normally non-coding, can sometimes be translated into proteins. This "accidental" protein production exposes a vast pool of potential new functionalities. Vakirlis et al. investigate how these "de novo emerging" coding sequences impact the fitness of yeast.

Fitness and the Unexpected Advantage of New Genes

The researchers disrupted these emerging sequences in the yeast genome. Surprisingly, these disruptions had little effect on the yeast's fitness in lab settings or natural populations. This implies that most newly formed genes are initially neutral – they neither harm nor benefit the organism. This challenges the positive selective tenet of neo-Darwinism.

However, the story takes a turn when the scientists overexpressed these de novo sequences. Overexpression essentially cranks up the production of the newly formed protein. Interestingly, this overexpression resulted in more frequent fitness benefits compared to overexpressing established genes. This suggests that while most new genes are initially neutral, some hold the potential to be advantageous when produced in higher quantities.

Thymine's Role in Building New Membrane Proteins

The study delves deeper, focusing on a specific type of protein: transmembrane proteins. These proteins span the cell membrane, playing crucial roles in communication, transport, and other cellular functions. Vakirlis et al. discovered that de novo emerging sequences enriched for genes encoding potential transmembrane domains.

Intriguingly, they found that intergenic regions (stretches of DNA between genes aka Junk DNA) rich in the nucleotide thymine (T) frequently harbored the potential to code for transmembrane domains. Thymine pairs with adenine (A) in DNA, and strings of Ts and As are more likely to code for hydrophobic amino acids, a key characteristic for membrane-spanning regions of proteins.

A New Model for Protein Evolution

Based on their findings, Vakirlis et al. propose a novel evolutionary model:

1. Thymine-rich intergenic regions hold the potential to code for transmembrane domains.

2. These regions are occasionally translated into polypeptides due to pervasive translation of non-coding transcripts.

3. The resulting polypeptides, if they contain transmembrane domains, might interact with the cell membrane in unexpected ways.

4. Over time, a previously non-coding sequence evolves into a functional de novo emerged transmembrane protein gene.

This model highlights the potential of thymine-rich regions as a breeding ground for new membrane proteins. It suggests a distinct pathway for protein evolution, where entirely new functionalities can arise from scratch, independent of existing genes and random mutations.

Looking Forward: Broader Implications and Future Research

The research by Vakirlis et al. opens doors to exciting new avenues in evolutionary biology. Here are some key takeaways and areas for future exploration:

• Evolutionary innovation: This study demonstrates a mechanism for the birth of entirely new protein functions, potentially accelerating adaptation apart from neo-Darwinism.

• Beyond yeast: Investigating if this model applies to other organisms, particularly multicellular ones with more complex genomes, would be crucial.

• Functional characterization: Understanding the specific functions of these de novo emerged proteins would provide deeper insights into their evolutionary significance.

• Regulation of de novo emergence: Are there mechanisms controlling the translation of these intergenic regions? Can we influence this process?

By exploring these questions, researchers can gain a richer understanding of how life evolves and create new functionalities. The ability to potentially nudge the process of de novo emergence could have significant implications for biotechnology and synthetic biology.

 Challenging Neo-Darwinism: New Genes From Scratch

The study "De novo emergence” proposes a novel mechanism for gene birth that challenges tenets of neo-Darwinism. Here's a breakdown:

• Neo-Darwinism: This theory emphasizes the role of mutations in existing protein coding genes and subsequent selection for beneficial traits. It suggests new genes arise through gradual modifications of existing ones.

• De novo Gene Birth: This study explores how entirely new protein-coding genes can emerge from scratch (de novo) in previously non-coding regions of the genome.

• Thymine-Rich Sequences: The research focuses on thymine-rich regions. Thymine (T) is one of the DNA building blocks, and these regions may possess a hidden potential to encode functional membrane proteins.

• The "TM-First" Model: The study proposes that under certain conditions, these thymine-rich regions might be translated into proteins with membrane-spanning domains. These domains allow proteins to interact with the cell's fatty barrier.

The Challenge: This "TM-first" model suggests the possibility of entirely new genes emerging with a pre-defined function (membrane interaction) without relying solely on mutations of existing genes. This challenges the neo-Darwinian view that new functionalities arise solely through gradual tinkering with existing ones.