hide
Free keywords:
-
Abstract:
It is widely accepted that new genes emerge from duplication and divergence from prior existing
genes. Improved methods of genome sequencing and comparison have led to the discovery of genes
that show no homologs outside of a given species or lineage. Since convergent gene loss in multiple
lineages or phases of accelerated evolution that led to loss of sequence similarity would be highly
uncommon, it is assumed that "orphan genes" have in fact arisen de novo from non-coding DNA.
Although there is strong evidence from the genomic point of view there is a lack of knowl- edge
regarding structure and function of de novo proteins.
One recent example of a structurally and functionally described de novo protein is Goddard in
Drosophila, which plays an important role during spermatogenesis (Lange et al., 2021). A continuing
problem remains the expression and purification of such proteins. Currently, we focus on how
chaperones (GroEL/GroES) influence the expressability and solubilty of de novo proteins from
Drosophila melanogaster and Homo sapiens in correlation to their disorder level.
We aim to express de novo proteins from different species with the help of chaperones in E. coli and
analyse them functionally for enzymatic activity, foldability, disorder and further elucidate their
structure in silico and experimentally via Cryo-EM and NMR.
Additionally, we use Ancestral reconstruction to investigate the emergence of de novo pro- teins and
how their sequence and structure alternated during the course of evolution. Exploration of naturally
arisen de novo proteins would give insights into early protein evolu- tion and broaden our knowledge of
the sequence space explored by nature on earth.
