The meanings of 'function' in biology and the problematic case of de novo gene emergence

Keeling, Diane Marie; Garza, Patricia; Nartey, Charisse Michelle; Carvunis, Anne‐Ruxandra

doi:10.7554/elife.47014

Cited by 65 publications

(63 citation statements)

References 45 publications

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“…A recent conceptualisation for defining de novo gene functionalisation [31] describes five levels of functional analysis. Our previous work on gdrd [30] addressed the gene's expression (a conserved, male-specific pattern across Drosophila species) and began to investigate the protein's evolutionary implications (conserved in most fly species except for D. willistoni) and capacities predicted to have one major α-helix with disordered termini).…”

Section: Introductionmentioning

confidence: 99%

Structural and functional characterization of a putativede novogene inDrosophila

Lange

Patel

Heames

et al. 2021

Preprint

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Comparative genomic studies have repeatedly shown that new protein-coding genes can emerge de novo from non-coding DNA. Still unknown is how and when the structures of encoded de novo proteins emerge and evolve. Combining biochemical, genetic and evolutionary analyses, we elucidate the function and structure of goddard, a gene which appears to have evolved de novo at least 50 million years ago within the Drosophila genus.Previous studies found that goddard is required for male fertility. Here, we show that Goddard protein localizes to elongating sperm axonemes and that in its absence, elongated spermatids fail to undergo individualization. Combining modelling, NMR and CD data, we show that Goddard protein contains a large central α-helix, but is otherwise partially disordered. We find similar results for Goddard’s orthologs from divergent fly species and their reconstructed ancestral sequences. Accordingly, Goddard’s structure appears to have been maintained with only minor changes over millions of years.

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Section: Introductionmentioning

confidence: 99%

Structural and functional characterization of a putativede novogene inDrosophila

Lange

Patel

Heames

et al. 2021

Preprint

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“…The question of what counts as “function” in a biological context is not straightforward. An interdisciplinary group of researchers have recently discussed the issue in relation specifically to de novo gene origin ( Keeling et al, 2019 ) and proposed five categories of meanings of function, pertaining to expression, capacities, interactions, physiology, and evolution. As they helpfully note, “Separating these meanings from one another enables communicating with increased precision about what the findings are, thereby helping to [avoid] fallacious logical shortcuts such as ‘this protein is expressed therefore it is functional therefore it is under selection.”’ Interestingly, they had limited success in actually applying their categorisation, with most instances in a test set of article abstracts not uniformly assigned to a category by different team members.…”

Section: Introductionmentioning

confidence: 99%

Are Antisense Proteins in Prokaryotes Functional?

Ardern

Neuhaus

Scherer

2020

Front. Mol. Biosci.

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Many prokaryotic RNAs are transcribed from loci outside of annotated protein coding genes. Across bacterial species hundreds of short open reading frames antisense to annotated genes show evidence of both transcription and translation, for instance in ribosome profiling data. Determining the functional fraction of these protein products awaits further research, including insights from studies of molecular interactions and detailed evolutionary analysis. There are multiple lines of evidence, however, that many of these newly discovered proteins are of use to the organism. Condition-specific phenotypes have been characterized for a few. These proteins should be added to genome annotations, and the methods for predicting them standardized. Evolutionary analysis of these typically young sequences also may provide important insights into gene evolution. This research should be prioritized for its exciting potential to uncover large numbers of novel proteins with extremely diverse potential practical uses, including applications in synthetic biology and responding to pathogens.

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“…However, having clear definitions and concepts about function are also highly relevant in scientific practice. [23] Microbiologist Jonathan L. Klassen recently argued for the importance of using clear definitions when using the term 'function' in microbiome research. [16] Besides discussing classical notions from philosophy, this raises important conceptual ques-tions about how we should think about microbiome function.…”

Section: What Does 'Function' Mean?mentioning

confidence: 99%

Microbiome Structure and Function: A New Framework for Interpreting Data

Greslehner

2020

BioEssays

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I suggest a distinction between different notions of 'structure' and 'function' for interpreting the overwhelming amount of data on microbiome structure and function: sequence data, biochemical agents, interaction networks, taxonomic communities, and their dynamics can be linked to potential or actual biochemical activities, causal roles, and selected effects, respectively. This conceptual clarification has important methodological consequences for how to interpret existing data and approach open questions in contemporary microbiome research practice. In particular, the field will have to start thinking about notions of function more directly.

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The meanings of 'function' in biology and the problematic case of de novo gene emergence

Cited by 65 publications

References 45 publications

Structural and functional characterization of a putativede novogene inDrosophila

Structural and functional characterization of a putativede novogene inDrosophila

Are Antisense Proteins in Prokaryotes Functional?

Microbiome Structure and Function: A New Framework for Interpreting Data

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