Nowick Lab

We submitted our manuscript on our study of functional relationships between KRAB-ZNF genes and transposable elements (TEs) to bioRxiv: “Regulatory networks of KRAB zinc finger genes and transposable elements changed during human brain evolution and disease”. In this work, Yao and Arnaud discovered that gene expression as well as regulation of TEs differs in the human brain compared to other primates. It also has changed in individuals with Alzheimer’s disease. To perform this comparative assessment of TE:KRAB-ZNF relationships, Yao developed an R package, called TEKRABber, which is publicly available on Bioconductor.

You have submitted your preprint entitled mtDNA “Nomenclutter” and its Consequences on the Interpretation of Genetic Data” to PCIEvolBiol, the Peer Community In for Evolutionary Biology. Baja and Vanessa describe very clearly the history of the nomenclature of human mitochondrial haplogroups, its inconsistencies, and what can go wrong if not properly applied in human population genetics studies.

We are happy to announce that we could finally hire Anne as our new technician. We are getting up to speed with our experiments 🙂

We have a new PhD student, Marula Mathew, who is strengthening the wetlab site of our team. Welcome Marula!

Laura Schmidt joined our team to work on gene regulatory factors with human specific changes. She will use primate iPSC to comparatively investigate how such factors might have contributed to unique pathways and expression patterns during human brain development.

On February 24th 2022 we gave a talk about our work for the general public at the Urania in Berlin. More than 100 people joined online and about 50 people had been in the auditorium. The talk is now available online and also here.

Title and abstract of our talk (in German):

Evolution des menschlichen Gehirns: Wie aus genetischen Änderungen kognitive Leistungen werden

Im Lauf der Evolution wurden menschliche Gehirne immer leistungsfähiger. Doch welche genetischen Änderungen führten dazu? Und wie testet man, ob und wie eine genetische Änderung kognitive Fähigkeiten ändert? Katja Nowick und Jeong-Eun Lee berichten, wie ihre Arbeitsgruppe mit bioinformatischen Methoden Gensequenzen findet, die spezifisch bei Menschen sind und für die Evolution unseres Gehirns relevant. Sie berichten, wie sie derartige Gensequenzen im Labor auf ihre Funktion hin testen.

Yao-Chung has developed an R package called TEKRABber to compare relationships between transposable elements (TEs) and genes between species. It is now available from Bioconductor:https://bioconductor.org/packages/3.15/bioc/html/TEKRABber.html.

Using RNA-Seq data, the package is normalizing expression values for genes and TEs across species and calculates correlations between TEs and genes. These correlations can then be compared between species to detect potential evolutionary differences in TE regulation and/or TEs influence on gene expression.

The name of the package derived from the idea that TEs are often repressed by KRAB-ZNF proteins.

Finally: After waiting for more than four years, we can start our first work in our brand new wetlab!

Because evolutionary changes in gene regulatory factors (GRFs), such as  transcription factors, can have a big impact on changing the phenotype between species, we set out to test all human GRFs proteins for positive selection within primates. Using information from 27 publicly available primate genomes we especially focused on the human lineage. From more than 3,000 human GRFs, we revealed with high confidence five GRFs that have been positively selected on the human lineage and one GRF that has been positively selected on the great ape lineage. Since each positively selected GRF contains several sites with evidence for positive selection, we suggest that these GRFs participated pleiotropically to phenotypic adaptations in humans.

Positive Selection in Gene Regulatory Factors Suggests Adaptive Pleiotropic Changes During Human Evolution

Vladimir M. Jovanovic, Melanie Sarfert, Carlos S. Reyna-Blanco, Henrike Indrischek, Dulce I. Valdivia, Ekaterina Shelest, and Katja Nowick

In an international collaboration we investigated the evolution of tissue-specific genes in the Lacerta viridis complex (European green lizard). We had sequenced and analyzed the genomes of three species/lineages and detected gene flow between the Adriatic lineage and L. viridis, suggesting that the evolutionary history of the L. viridis complex is likely shaped by gene flow. Genes highly expressed in the ovaries experienced accelerated evolution presumably contributing to establishing reproductive isolation in the Lacerta viridis complex. In addition, we built co-expression networks and found that genes that are strongly co-expressed in the brain also show accelerated evolution, potentially pointing to the evolution of behavioral differences between the species. Such accelerated evolution of tissue-specific genes might allow for speciation amidst gene flow in European green lizards.

Accelerated evolution of tissue-specific genes mediates divergence amidst gene flow in European green lizards

Sree Rohit Raj Kolora, Deisy Morselli Gysi, Stefan Schaffer, Annegret Grimm-Seyfarth, Márton Szabolcs, Rui Faria, Klaus Henle, Peter F Stadler, Martin Schlegel, Katja Nowick