Biology subjects

Lebherz, M. K.

Publications and source records attributed to Lebherz, M. K..

3 recordsLinked to original sources

bioRxiv2024

De novo ORFs are more likely to shrink than to elongate during neutral evolution.

For protein coding genes to emerge de novo from a non-genic DNA, the DNA sequence must gain an open reading frame (ORF) and the ability to be transcribed. The newborn de novo gene can further evolve to accumulate changes in its sequence. Consequently, it can also elongate or shrink with time. Existing literature shows that older de novo genes have longer ORF, but it is not clear if they elongated with time or remained of the same length since their inception. To address this question we developed mathematical model of ORF elongation as a Markov-jump process, and show that ORFs tend to keep their length in short evolutionary timescales. We also show that if change occurs it is likely to be a truncation. Our genomics and transcriptomics data analyses of seven Drosophila melanogaster populations is also in agreement with the models prediction. We conclude that selection could facilitate ORF length extension that may explain why longer ORFs were observed in old de novo genes in studies analysing longer evolutionary time scales. SignificanceNew protein coding genes can emerge from non-genic DNA through a process called de novo gene emergence. Genes thus emerged usually have a small open reading frame (ORF). However, studies show that de novo genes with an older evolutionary origin have longer ORF than younger genes. To understand how ORF length evolves, we use a combination of mathematical modeling and population level genome data analysis. We find that in the absence of evolutionary selection, ORFs tend to become shorter than becoming longer. Therefore, long ORFs are probably selected by evolution to be retained in the genome.

evolutionary biology↗

bioRxiv2023

DNA Transposons favour de novo transcript emergence through enrichment of transcription factor binding motifs

De novo genes emerge from non-coding regions of genomes via succession of mutations. Among others, such mutations activate transcription and create a new open reading frame (ORF). Although the mechanisms underlying ORFs emergence are well documented, relatively little is known about the mechanisms enabling new transcription events. Yet, in many species a continuum between absent and very prominent transcription has been reported for essentially all regions of the genome. In this study we searched for de novo transcripts by using newly assembled genomes and transcriptomes of seven inbred lines of Drosophila melanogaster, originating from six European and one African population. This setup allowed us to detect line specific de novo transcripts, and compare them to their homologous non-transcribed regions in other lines, as well as genic and intergenic control sequences. We studied the association with transposable elements and the enrichment of transcription factor motifs upstream of de novo emerged transcripts and compared them with regulatory elements. We found that de novo transcripts overlap with TEs more often than expected by chance. The emergence of new transcripts correlates with high CpG islands and regions of TEs activity. Moreover, upstream regions of de novo transcripts are highly enriched with regulatory motifs. Such motifs abound in new transcripts overlapping with TEs, particularly DNA TEs, and are more conserved upstream de novo transcripts than upstream their non-transcribed homologs. Overall, our study demonstrates that TEs insertion is important for transcript emergence, partly by introducing new regulatory motifs from DNA TE families.

genomics↗

bioRxiv2022

Population genomics reveals mechanisms and dynamics of de novo proto-gene emergence in Drosophila melanogaster

Scientific AbstractNovel genes are essential for evolutionary innovations and differ substantially even between closely related species. Recently, multiple studies across many taxa have suggested that some novel genes arise de novo, i.e. from previously non-coding DNA. In order to characterise the underlying mutations that allowed de novo gene emergence and their order of occurrence, homologous regions must be detected within non-coding sequences in closely related sister genomes. So far, most studies do not detect non-coding homologs of de novo genes due to inconsistent data and long evolutionary distances separating genomes. Here we overcome these issues by searching for proto-genes, the not-yet fixed precursors of de novo genes that emerged within a single species. We sequenced and assembled genomes with long-read technology and the corresponding transcriptomes from inbred lines of Drosophila melanogaster, derived from seven geographically diverse populations. We found line-specific proto-genes in abundance but few proto-genes shared by lines, suggesting a rapid turnover. Gain and loss of transcription is more frequent than the creation of Open Reading Frames (ORFs), e.g. by forming new START- and STOP-codons. Consequently, the gain of ORFs becomes rate limiting and is frequently the initial step in proto-gene emergence. Furthermore, Transposable Elements (TEs) are major drivers for intra genomic duplications of proto-genes, yet TE insertions are less important for the emergence of proto-genes. However, highly mutable genomic regions around TEs provide new features that enable gene birth. In conclusion, proto-genes have a high birth-death rate, are rapidly purged, but surviving proto-genes spread neutrally through populations and within genomes.

genomics↗