Songbird genome to aid understanding of learning, memory and more

The zebra finch offers a unique opportunity for us to understand the genetics behind the wiring and re-wiring of our brains when we learn and memorise, as well as many other individual features such as immunity and fertility. It will also reveal the genetics underpinning some of the uniquely fascinating traits of birds such as plumage and song. Teams across the USA, Europe and the Middle East, including seven UK-based research groups, have contributed to this substantial project, which includes funding from the Biotechnology and Biological Sciences Research Council (BBSRC).

Professor Douglas Kell, BBSRC Chief Executive said: "Genome data like these are extremely valuable and it is really important to fulfil the potential of such information. There is considerable excellence in the UK in bioinformatics and we are thinking hard about how best to make these large collections of data and metadata available in the most useful form for researchers. We are committed to this end and BBSRC has considerable expertise amongst our community of researchers and in the BBSRC funded institutes."

Mick Watson, an author on the paper and Head of Bioinformatics at the Institute for Animal Health said: "To understand a genome, we need more than just the DNA sequence itself. Many scientists must work together to define which parts of the DNA are functional, and what they do."

Professor Dave Burt, an author on the paper and head of Avian Genomics at The Roslin Institute, University of Edinburgh said: "The input of many biologists has been crucial to build our knowledge of the zebra finch genome. Having both the zebra finch and chicken genomes sequenced helps us to understand more about the biology and evolution of birds and the comparison of the zebra finch genome with others allowed us to define the genes. At The Roslin Institute we have gone on to use additional information from the chicken and human genomes to identify the function of more than 80% of the defined zebra finch genes."

Mr Watson continued: "When researchers generate data about gene expression, we need powerful computer tools in order to understand what the data tells us."

Two UK based bioinformatics tools -- the Ensembl resource which is co-developed and jointly run by the European Bioinformatics Institute (EMBL-EBI) and the Wellcome Trust Sanger Institute, and the CORNA software developed by the Bioinformatics Group at the Institute for Animal Health, an institute of BBSRC -- were vital for drawing out crucial information from data in this project.

Dr Paul Flicek, an author on the paper and joint head of Ensembl said: "Having a second bird genome helps us to understand vertebrate evolution. Using Ensembl we were able to identify the genes in the zebra finch genome and find the evolutionary relationships between zebra finch genes and those in other species. By doing this we can identify characteristic evolutionary features that are common to birds and mammals, as well as those evolutionary features that distinguish mammals from birds."

Mr Watson concluded: "This broad collaboration has allowed a large group of researchers to work together to share data, knowledge, tools and expertise to produce a meaningful genome sequence that will be invaluable to many areas of research."

The work to produce this genome sequence is funded by the National Human Genome Research Institute (NHGRI) with additional support in the form of grants to some of the researchers from other funding bodies in the USA and Europe, including the Biotechnology and Biological Sciences Research Council (BBSRC) in the UK.

The seven UK groups are at EMBL-EBI and the Wellcome Trust Sanger Institute in Cambridge, the MRC Functional Genomics Unit at the University of Oxford, the Institute for Animal Health (IAH) in Berkshire, University of Kent, University of Sheffield and The Roslin Institute at the University of Edinburgh. BBSRC provides institute strategic research grants to IAH and The Roslin Institute as well as grant funding to the groups at University of Oxford, University of Kent and University of Sheffield.

Insights from the zebra finch genome:

Learning and Memory

Zebra finches and other songbirds have one important thing in common with humans: they learn how to converse with one another, which is very rare in other animals. Chickens (the only other bird we have a genome sequence for) do not demonstrate this kind of vocalisation and so a comparison between the zebra finch and chicken genomes has helped to identify where the genes that are directly involved in vocal learning are located.

It has been known for a while that listening to songs turns genes on or off in certain areas of the brain of a zebra finch. This project has shown that there are also important changes in what the genome actually produces when a young male zebra finch first learns his song from an adult tutor.

Professor Chris Ponting, an author on the paper from the MRC Functional Genomics Unit at the University of Oxford said: "Normally we think of genomes providing a blueprint for making only proteins, but there are indications here that song stimulates the zebra finch to turn off the production of even more exotic molecules called RNAs."

The next stage will be to investigate whether these RNAs play roles in learning and memory for the zebra finch, or even for humans.

Variation and Evolution

Professor Darren Griffin, an author on the paper from the University of Kent said: "One of our key findings was the genetic basis of a lot of the variation between chickens and zebra finches. Clearly the two birds are very different but the evidence we had before suggested their genomes were actually very similar. In fact, we now have a clear idea of why this is not the case."

Professor Griffin continued: "The chicken was a great start for genomic studies because of the agricultural and embryology angle. In evolution chickens are a bit out on a limb and the zebra finch is a much better representative of the majority of birds."

Dr Jon Slate, an author on the paper from University of Sheffield said: "The zebra finch is a useful model for research and the genome information provides the tools we need to find genes responsible for the remarkable diversity of plumage, song and behaviour that we see in birds -- features that have fascinated biologists and ornithologists for centuries.

"Because we work with a well established population of zebra finches at Sheffield, we could look at the inheritance of genes across several generations. This was incredibly useful when we were building the genetic map that formed the scaffolding for this genome sequencing project."

Professor Griffin concluded: "From here, we can use the information and tools that we have developed to study many aspects of bird evolution and ecology. Many birds are among the most threatened species in the world, particularly with impending climate change."

Immunity

Professor Dave Burt, an author on the paper from The Roslin Institute said: "Having the chicken genome sequenced helped to inform us about the zebra finch but it also worked both ways, with the zebra finch genome telling us more about the chicken. At The Roslin Institute we were able to use this link to discover a gene previously thought to be missing in birds, the Colony Stimulating Factor 1 protein (CSF1). This gene is found in mammals and is important in fighting infections, and was identified in the zebra finch and with a bit of detective work we then discovered it in the chicken. This will then help us develop new ways of producing vaccines to prevent disease in birds."

Dr Robert Ekblom, a member of the University of Sheffield team, also identified genes in the zebra finch genome that were related to immunity. By comparing these to their equivalents in other species it will be possible to understand the evolution of immunity -- in particular to parasites.

Fertility

Dr Jon Slate and Professor Tim Birkhead at the University of Sheffield have discovered that there is a genetic component to sperm length and speed in the zebra finch. This means that the genome could be invaluable for research into human fertility. Dr Slate said: "Discovering the genes that explain these differences in fertility is now possible, and it is likely that the same genes will have similar effects in humans as well."