Biochemical constraints on genes involved in early embryonic development.

Sandeep Venkataram is a graduate student in the Petrov lab.

Post author Sandeep Venkataram is a graduate student in the Petrov lab.

Chemical reactions form the foundation of life, yet such elementary activities are rarely considered when trying to understand higher-level processes, such as embryonic development. Nevertheless, as recently shown by Artieri and Fraser (MBE 2014), limitations on the kinetics of gene expression strongly constrain the length of highly expressed transcripts during early embryonic development of fruit flies. Furthermore, this phenomenon appears to be a general feature of fruit fly development as it is evolutionarily conserved across a number of species.

The long and short of mRNA transcription

It has long been known that only a portion of the mRNA molecules are used to produce functional proteins – multicellular species contain many long ‘introns’, which must first be transcribed, then spliced out before translation can occur. Introns can be very long, causing transcription of some mRNA molecules to take significant amounts of time: for example, one 2.3 million bp transcript in humans takes over half a day to be produced. This creates a problem as incompletely transcribed mRNA molecules are degraded when DNA is replicated at the beginning of cell division, and the process must begin anew once division is completed. Together, this implies that cell divisions need to be spaced out long enough apart from each other to produce all of the transcripts necessary for the growth of the cell before the next division occurs.

Studies of fruit fly development have shown that zygotes undergo “syncytial division” at the beginning of development, where the DNA within the zygotic nuclei divide every ~10 minutes for 9 cycles, followed by 4 additional progressively lengthening divisions. While most mRNA in the cell at this time are supplied by the mother (maternal mRNA), this also represents the phase during which the zygote begins producing its own mRNA. The extremely rapid cell divisions led Artieri and Fraser to hypothesize that long mRNA molecules transcribed from the zygotic genome may be underrepresented during these early stages of development. Maternal mRNAs, on the other hand, would be unaffected as they are already present in the cell and do not have to be transcribed.

Transcript length vs. developmental timing

The authors classified embryonically expressed genes as “maternal” or “zygotic” depending on whether or not the gene was present as maternal mRNA in unfertilized embryos using published data. They then obtained multiple developmental mRNA expression timecourses and found that long zygotically expressed genes took longer to reach maximal expression levels than short genes – consistent with their inability to be fully transcribed during early development (Figure 1). Furthermore, they were able to use total RNA expression data to detect the presence of incomplete transcripts, indicating that delay was not due to later transcriptional activation, but rather the incomplete production of transcripts.

Modified from Artieri and Fraser 2014 Figure 2B . Long zygotic genes are underexpressed early in the syncytial division phase relative to short genes, but catch up in expression by the end of the syncytial phase while maternally derived transcripts show no such changes.

Figure 1. Long zygotic genes are underexpressed early in the syncytial division phase relative to short genes, but catch up in expression by the end of the syncytial phase while maternally derived transcripts show no such changes. [Modified from Artieri and Fraser 2014 Figure 2B . ]

Using a published set of developmental mRNA expression timecourses from additional Drosophila species, Artieri and Fraser show that these patterns are consistent across all species examined. Finally, they also observed that the introns present in highly expressed zygotic genes appear to be highly evolutionarily constrained in terms of their lengths when compared to either genes maternally deposited or zygotically expressed during later timepoints. This suggests that natural selection has played a role in limiting the expansion of introns in early expressed zygotic genes, allowing them to escape ‘intron delay’.


In summary, Artieri and Fraser have found evidence that a significant fraction of zygotically expressed transcripts in fruit flies are delayed from reaching their maximal levels of expression due to the rapid cell cycles taking place at the beginning of development. This suggests a simple mechanism for developmental timing of zygotic gene expression: genes that are required early must be short, while genes whose expression is needed at a later time can delay their expression via the presence of long introns. While some evidence for the use of intron length as a regulatory mechanism has recently emerged (Takashima et al. 2011), future experiments will be required to determine how widespread is the effect of selection to maintain long lengths and delayed expression.


Carlo G. Artieri and Hunter B. Fraser Transcript Length Mediates Developmental Timing of Gene Expression Across Drosophila. (2014) Molecular Biology and Evolution doi:10.1093/molbev/msu226

Takashima Y, Ohtsuka T, González A, Miyachi H, Kageyama R. Intronic delay is essential for oscillatory expression in the segmentation clock. Proc Natl Acad Sci U S A. 2011;108:3300-3305.

Paper author Carlo Artieri is a postdoctoral fellow in the Fraser lab.

Paper author Carlo Artieri is a postdoctoral fellow in the Fraser lab.


The fruit fly and its microbiome


Philipp Messer is a research associate in the Petrov lab

This post was written by Philipp Messer.

Although fruit flies are one of the most important model organisms in genetics, evolution, and immunology, surprisingly little is known about their associated microorganisms (their microbiome). This is even the more surprising if you consider that the microbiome can strongly affect quantitative traits in flies, for example their growth rate and cold tolerance. Furthermore, the natural environment of fruit flies – rotting fruit – is very rich in microorganisms.

All organisms interact with associated microbes

Because microbes can influence the phenotype of organisms, we expect such interactions to be subject to natural selection. Genes involved in pathogen defense are indeed amongst the fastest evolving genes. But interactions with microbes do not always just lead to an evolutionary arms race between microbes and their hosts, they can also facilitate major evolutionary innovations. Prominent examples of such innovations are the light organ of the bobtail squid that arose through a symbiotic relationship between squids and bioluminescent bacteria, or cellulose digestion in termites which relies on microbes in their guts. Hence, to improve our understanding of the evolution of fruit flies, we need to better understand how they interact and coevolve with their associated microorganisms.

In their paper “Host species and environmental effects on bacterial communities associated with Drosophila in the laboratory and in the natural environment”, Fabian Staubach and his colleagues at Stanford and the Max Planck Institute for Evolutionary Biology in Plön shed light on some of the major questions regarding Drosophila associated microbes. Beyond finding out which bacteria are present in flies, they assess the relative roles of host species and environmental effects on bacterial communities, detect candidate natural pathogens, and find interesting results regarding lab-of-origin-effects on the fly microbial community.

The microbiome of fruitflies

We need more studies like this

These results are not only highly relevant for everyone working with Drosophila, but are also a strong reminder that we cannot understand any model organism without taking its associated microbiota into account. We therefore need more microbiome studies like that of Staubach et al to identify the microbes that coevolve with their hosts and understand how the genomes of hosts and microbes interact in the evolutionary process. I would not be surprised if interactions between microbes and their hosts turn out to be among the biggest selective forces in many organisms.

The paper is a fun and easy read and can be found at here. Fabian was a postdoc in the Petrov lab from 2010 to 2013 and has just moved to the University of Freiburg in Germany to start his own group, where he plans to follow his interest to deepen our understanding of the role of microbes in adaptation.

Citation: Staubach F, Baines JF, Künzel S, Bik EM, Petrov DA (2013) Host Species and Environmental Effects on Bacterial Communities Associated with Drosophila in the Laboratory and in the Natural Environment. PLoS ONE 8(8): e70749. doi:10.1371/journal.pone.0070749


Fabian Staubach studies the microbiome of fruitflies.