Researchers have determined that there are hundreds of biological differences between the sexes when it comes to gene expression in the cerebral cortex of humans and other primates.  These findings, published June 20th in the open-access journal PloS Genetics, indicate that some of these differences arose a very long time ago and have been preserved through evolution.  These conserved differences constitute a signature of sex differences in the brain.

Many more obvious gender differences have been preserved throughout primate evolution; examples include average body size and weight, and genitalia design.  This study, believed to be the first of its kind, focuses on gene expression within the cerebral cortex.  The cerebral cortex is involved in many of the more complex functions in both humans and other primates, including memory, attentiveness, thought processes and language.

The researchers measured gene expression in the brains of male and female primates from three species: humans, macaques, and marmosets.  To measure activity of specific genes, the products of genes (RNA) obtained from the brain of each animal were hybridized to microarrays containing thousands of DNA clones coding for thousands of genes.  The authors also investigated DNA sequence differences among primates for genes showing different levels of expression between the sexes.

“Knowledge about gender differences is important for many reasons.  For example, this information may be used in the future to calculate medical dosages, as well as for other treatments of diseases or damage to the brain,” says team leader Professor Elena Jazin, at Uppsala University, Sweden.

In addition to the results mentioned above, the researchers also report on evolutionary speeds in genes that have been identified as male or female-oriented.  This could provide clues about the power of natural selection processes during the evolution of primates.

Lead author Björn Reinius notes that the study does not determine whether these differences in gene expression are in any way functionally significant.  Such questions remain to be answered by future studies.

What makes a human different from a chimp?  Researchers from the European Molecular Biology Laboratory’s European Bioinformatics Institute [EMBL-EBI] have come one important step closer to answering such evolutionary questions correctly.  In the current issue of Science they uncover systematic errors in existing methods that compare genetic sequences of different species to learn about their evolutionary relationships.  They present a new computational tool that avoids these errors and provides accurate insights into the evolution of DNA and protein sequences.  The results challenge our understanding of how evolution happens and suggest that sequence turnover is much more common than assumed.

“Evolution is happening so slowly that we cannot study it by simply watching it.  That’s why we learn about the relationships between species and the course and mechanism of evolution by comparing genetic sequences,” says Nick Goldman, group leader at EMBL-EBI.

The four letter code that constitutes the DNA of all living things changes over time; for example individual or several letters can be copied incorrectly [substitution], lost [deletion] or gained [insertion].  Such changes can lead to functional and structural changes in genes and proteins and ultimately to the formation of new species.  Reconstructing the history of these mutation events reveals the course of evolution.

A comparison of multiple sequences starts with their alignment.  Characters in different sequences that share common ancestry are matched and gains and losses of characters are marked as gaps.  Since this procedure is computationally heavy, multiple alignments are often built progressively from several pairwise alignments.  It is impossible, however, to judge if a length difference between two sequences is a deletion in one or an insertion in the other sequence.  For correct alignment of multiple sequences, distinguishing between these two events is crucial.  Existing methods, that fail to do that, lead to a flawed understanding of the course of evolution.

“Our new method gets around these errors by taking into account what we already know about evolutionary relationships,” says Ari Löytynoja, who developed the tool in Goldman’s lab.  “Say we are comparing the DNA of human and chimp and can’t tell if a deletion or an insertion happened.  To solve this our tool automatically invokes information about the corresponding sequences in closely related species, such as gorilla or macaque.  If they show the same gap as the chimp, this suggests an insertion in humans.”

Findings achieved with the new technique suggest that insertions are much more common than assumed, while the frequency of deletions has been overestimated by existing methods.  A likely reason for these systematic errors of other techniques is that they were originally developed for structural matching of protein sequences.  The focus of molecular biology is shifting, however, and understanding functional changes in genomes requires specifically designed methods that consider sequences’ histories.  Such approaches will likely reveal further bugs in our understanding of evolution in future and might challenge the conventional picture of sequence evolution.

The immune system of vertebrate animals consists of two components: the innate immune response, a constitutive system ready to respond to a pathogen, and the adaptive immune response, a system of immunological memory that responds to previously encountered pathogens. In a study led by Dr. Anlong Xu of Sun Yat-sen University, scientists searched the amphioxus genome for genes that may be relevant to immunity in order to gain an understanding of what the immune system repertoire of the vertebrate ancestor may have looked like. “Our chordate ancestors had a remarkably elaborate innate immune system, but this system was somehow reduced in the vertebrate lineage, which is unusual to our conventional thinking of the immune system,” explains Xu. Furthermore, Xu notes that this work helps to describe a global picture of innate immunity and uncover the evolutionary footsteps underlying the evolution of human immune pathways.

Scientists funded by the Biotechnology and Biological Sciences Research Council (BBSRC) have discovered how evolution may have lumbered humans with allergy problems. The team from the Randall Division of Cell & Molecular Biophysics, King’s College London are working on a molecule vital to a chicken’s immune system which represents the evolutionary ancestor of the human antibodies that cause allergic reactions. Crucially, they have discovered that the chicken molecule behaves quite differently from its human counterpart, which throws light on the origin and cause of allergic reactions in humans and gives hope for new strategies for treatment. The work is published today (13 June) in The Journal of Biological Chemistry.

Researcher, Dr Alex Taylor said: “This molecule is like a living fossil – finding out that it has an ancient past is like turning up a coelacanth in your garden pond. By studying this molecule, we can track the evolution of allergic reactions back to at least 160 million years ago and by looking at the differences between the ancient and the modern antibodies we can begin to understand how to design better drugs to stop allergic reactions in their tracks.”

The chicken molecule, an antibody called IgY, looks remarkably similar to the human antibody IgE. IgE is known to be involved in allergic reactions and humans also have a counterpart antibody called IgG that helps to destroy invading viruses and bacteria. Scientists know that both IgE and IgG were present in mammals around 160 million years ago because the corresponding genes are found in the recently published platypus genome. However, in chickens there is no equivalent to IgG and so IgY performs both functions.

Lead researcher, Dr. Rosy Calvert said: “Although these antibodies all started from a common ancestor, for some reason humans have ended up with two rather specialised antibodies, whereas chickens only have one that has a much more general function.

“We know that part of the problem with IgE in humans is that it binds extremely tightly to white blood cells causing an over-reaction of the immune system and so we wanted to find out whether IgY does the same thing.”

By examining how tightly IgY binds to white blood cells the researchers have found that it behaves in a much more similar way to the human IgG, which is not involved in allergic reactions and binds much less tightly.

Professor Brian Sutton, head of the laboratory where the work was done said: “It might be that there was a nasty bug or parasite around at the time that meant that humans needed a really dramatic immune response and so there was pressure to evolve a tight binding antibody like IgE. The problem is that now we’ve ended up with an antibody that can tend to be a little over enthusiastic and causes us problems with apparently innocuous substances like pollen and peanuts, which can cause life-threatening allergic conditions.”

The next stage of the work is to examine in very fine detail the interaction between the antibodies and the surface of the white blood cell. This is with a view to designing drugs that could alter this interaction and therefore ‘loosen’ the binding of IgE, making it more like its chicken counterpart.

Nautiloids are the sole surviving family of externally-shelled cephalopods that thrived in the tropical oceans 450–150 million years ago. However, in the intervening years their modern soft bodied relatives dumped the shell and developed complex central nervous systems; which makes Nautilus ideally suited to discover the ‘evolutionary pathways that led to the development of the complex coleoid [soft bodied cephalopod] brains’ say Robyn Crook and Jennifer Basil. Knowing that the simple Nautilus brain lacks the structures required for memory in more sophisticated cephalopods, Crook and Basil decided to test the living fossil’s memory.

Training Nautilus pompilus to associate the smell of food with a blue light, the cephalopods eventually learned to respond to a flash of blue light by extending their tentacles. Then the scientists tested the cephalopods memories with a flash of light 3min, 30min, 1h, 6h, 12h and 24h after training. Amazingly, Nautilus remembered their training for up to an hour before the memory was lost, but then the memory returned 6h later, lasting up to 24h. Nautilus has both short and long term memory, just like modern cephalopods, despite lacking the same brain structures.

Crook and Basil are optimistic that the unsophisticated Nautilus brain could teach us how modern cephalopod brains evolved.