Update on 10,000 genomes and tasmanian devils

September 27, 2010

A while back I wrote about the Genome 10K project, an ambitious initiative from a consortium of mostly US-based researchers to sequence 10,000 vertebrate genomes.  Recently BGI (formerly known as the Beijing Genomics Institute)  embarked on a similar project, aiming to sequence 1000 plant and animal genomes to create a library of digital life, and in May they announced that they would sequence the first 100 vertebrate genomes for the Genome 10K project.   BGI have invested $100m into the digital library project, enabling them to fully fund some genome projects, and partially fund others.

The 100 species to be included in the Genome 10K project are being chosen on the basis of their biology, diversity, specimen availability, and the existence of a scientific community with expertise in the species.  And if your favourite genome is not on their current to-do list, don’t despair, as BGI are calling for proposals for other genomes to sequence.

Last week I went along to a seminar by representatives from BGI at Victoria University.  I was kind of blown away by their the sheer size and scale of their operation – they have a workforce of about 3000 people and billions of dollars in facilities all dedicated to pumping out and assembling DNA sequence, and really seem to be taking over the world when it comes to genomics.

But one genome that BGI hasn’t been sequencing is the tasmanian devil.  Its been a big month for tassie devil news:  first from the fight against devil facial tumour disease,  the news that Cedric, an animal with a putative “resistant” genotype, had died of the disease; and secondly the announcement that the tasmanian devil genome has been sequenced.  The genome was sequenced by the Wellcome Trust Sanger Institute in the UK.  They have  sequenced the genome of a healthy tasmanian devil plus two independent tumour samples, in the hope that they will be able to pinpoint mutations that will improve understanding of the disease and how it spreads.

Genomics tidbits

July 14, 2010

Its been a little quiet round these parts over the past month, as the daily juggle between motherhood, work and blogging usually ends in me dropping the blogging ball.  I do have a couple of posts in the works, but in the meantime here’s a few tidbits from the past week in the genomics world to keep ya’ll occupied…

A new group blog on personal genomics called Genomics Unzipped has hit the blogosphere.  According to their inaugural post, they aim to “provide you with independent analysis of advances in the field of genetics, with a particular focus on implications for the budding industry of personal genomics. We’ll also be discussing ways in which you can make the most of your own genetic data using online resources and techniques developed by researchers”.  Several established bloggers will be contributing to Genomics Unzipped, including Genetic Future‘s Daniel MacArthur, Genomics Law Report‘s Dan Vorhaus, Luke Jostins from Genetic Inference

The genome of Volvox carteria multicellular algae, was published in the latest issue of Science.  The genome is a step forward for US Department of Energy researchers investigating how photosynthetic organisms convert sunlight to energy for potential sources of biofuels.   The researchers compared the genome of V. carteri with that Chlamydomonas reinhardtii, a unicellular algae used extensively for research on potential algal biofuel generation.  There were surprisingly few differences between the two genomes, suggesting that the evolution of multicellularity (there’s a mouthful) is not as complicated as once thought.

Another paper published in Science claiming to have identified genetic signatures of longevity appears to have a few major flaws.  Genetic future and Newsweek have more…

Tuatara holds clues to human evolution

June 16, 2010

ResearchBlogging.orgA while ago I wrote about the value of genome sequences, not just for helping us understand the biology of a particular organism, but also for enabling large-scale comparisons across species that can help spot patterns in genome evolution which wouldn’t otherwise be apparent.  A recent paper in Journal of Heredity by Craig Lowe, David Haussler and colleagues at the University of California provides an excellent example of this in action, using sequences from the tuatara genome to identify the evolutionary origin of parts of the human genome.

Lowe and colleagues were looking for functional elements (like parts of genes and their regulatory regions) in the human genome that originated from retrotransposon insertions.  Retrotransposons are mobile bits of DNA that have a tendency to make copies of themselves and insert themselves in various different places in the genome.  They contain everything needed for this copying, plus often include functional modules like exons of genes, or transcription factor binding sites.  These functional modules may be co-opted for a new function in the new site, a process known as exaptation.  Once a retrotransposon is inserted in a new location it is often inactivated, and then begins to accumulate mutations which render it unrecognisable as a retrotransposon. This makes it difficult to identify exaptation events in any given genome and hence trace the origin of many of the functional elements of that genome.  However, by comparing the genomes of many different species in different lineages it may be possible to identify ancestral versions of these elements, and so trace their evolutionary history.

Lowe and colleagues found a previously unknown retrotransposon in the small part of the tuatara genome that has been sequenced.  This retrotransposon is of a type known as a LINE – Long Interpersed Nucleotide Element – and was named EDGR-LINE  (endangered-LINE).  A search of human genome against this sequence found 18 elements that are likely to be the result of insertion of this retrotransposon into the genome at some point in evolutionary time.  Seventeen of these elements are gene regulatory regions and one is an exon of a gene called ASXL3.  ASXL3 is important for regulation of other genes during development and the additional exon co-opted from EDGR-LINE appears to help control its expression.

These 18 exaptation events likely occurred early in mammalian evolution, but the retrotransposon itself has long since been inactivated in humans so all traces of it have been lost.  The functional elements it contained are able to be identified because they are under strong purifying selection (i.e. have not accumulated many mutations), so can still be aligned with the tuatara sequence.  Its only through this comparison that it is possible to know that these 18 elements originated from the same retrotransposon.

EDGR-LINE was also found in the lizard, frog, and coelecanth, but no traces of it remain in mammals, crocodylia and birds.  EDGR-LINE appears to be more slowly evolving in tuatara than in lizards, so is closest to the mammalian ancestral version of EDGR-LINE and hence more informative for identifying elements in the human genome. In fact, 10 of the 18 elements could only be identified by comparison with tuatara and not with these other species.

Evolution of the EDGR-LINE in vertebrates. The EDGR-LINE appears to have been introduced in the common ancestor of tetrapods and lobe-finned fish, and lineages where the LINE was active are shown with green. The LINE is not noticeable in mammals, crocodylia, aves, or testudines, so it has already been inactivated at least twice in evolution.

This is not the only example of genomic information from a rare species shedding light on the evolutionary history of human genome.  The genome of the threatened desert tortoise Gopherus agassizii also harbours an ancient LINE that has enabled functional elements of the human genome to be identified.  Lowe and colleagues speculate that this may be due to the very nature of endangered species, and ran simulations to show that theoretically, mobile elements like LINEs are active for longer and evolve more slowly in small populations.   This effect comes about because of the relationship between population size and selection – selection is more efficient in large populations so is more likely to remove genetic variants which are mildly harmful (or deleterious) to the organism, and to fix mutations which are beneficial.  The smaller the population, the more likely it is that deleterious genetic variants will become fixed in that population and beneficial mutations will be removed.  Insertion of mobile elements into new places in the genome is almost always deleterious, as it messes with existing genes and their regulatory regions.  Thus small populations will be more likely to accumulate additional copies of the mobile elements, and less likely to accumulate mutations which would remove or inactivate them.  I should point out here that tuatara are not actually classified as endangered (as the paper claims), but they have had a historically low population size, with probably a severe population bottleneck during the oligocene inundation of the New Zealand land mass.  In addition, we now know that even large tuatara populations can have a small effective population size, as few individuals actually contribute to mating at any one time.

Lowe and colleagues point out that without the tuatara, we would not have been able to identify these particular functional elements in the human genome, and that we never know what additional information about human evolution we might glean from threatened species in the future.  This underscores the importance of projects like the Genome10K initiative to sequence 10,000 vertebrate genomes.  Of course I would add that we should preserve these species for their intrinsic worth not just because of what they can tell us about human evolution, but this paper does highlight the unexpected ways that genomic data from diverse species can help us understand evolution.

Lowe, C., Bejerano, G., Salama, S., & Haussler, D. (2010). Endangered Species Hold Clues to Human Evolution Journal of Heredity DOI: 10.1093/jhered/esq016

Cloning extinct species #2: Should we bother?

May 10, 2010

Two weeks ago I posted about how, theoretically at least, one could go about bringing an extinct species back to life by cloning.  Its clear that for long-extinct species like the mammoth, where only degraded remains are available, cloning is still a very long way off and in fact may not ever be possible.  But for species that have only recently gone extinct, or are on the verge of extinction, correct preservation of tissues could see clones created (in fact this has already happened in the case of the pyrenean ibex).  But should we bother going down this path? Read the rest of this entry »

Cloning extinct species #1: A how-to guide

April 30, 2010
 Fancy seeing herds of mammoths running across the tundra, moa crashing through the undergrowth, or perhaps a tasmanian tiger lurking in the Aussie bush? Well in the near future these images might not just be the stuff of far-fetched Hollywood movie plots.  Advances in molecular biology and genomics mean that the ability to clone extinct species is getting closer. In theory, at least.  In this post I’m going to look at how one would go about bringing back to life their favourite extinct species, and in a later post I’ll discuss whether we should bother. Read the rest of this entry »

Songbird genome published

April 1, 2010

The genome of the zebra finch was published in Nature today and is free to access here. This is the second bird species to have its genome published – the other one being the chicken.  The zebra finch is a member of the Order Passeriformes (the songbirds) and is something of a model organism in neurophysiology.  Not surprisingly its genome has a number of interesting features associated with song and vocal communication.  I hope to have some time to write more about the songbird genome later but in the meantime here’s a summary from Nature:

The genome of the zebra finch — a songbird and a model for the study of vertebrate brain, behaviour and evolution — has been sequenced. Its comparison with the chicken genome, the only other bird genome available, shows that genes with neural function and implicated in cognitive processing of song have been rapidly evolving in the finch lineage. The study also shows that vocal communication engages much of the zebra finch brain transcriptome and identifies a potential integrator of microRNA signals linked to vocal communication.

Male zebra finch (photo from Wikimedia Commons)

So what is a gene, exactly?

December 13, 2009

Ever wondered just what a “gene” is, exactly? Well turns out that even geneticists are wondering the same thing these days, as they learn more about the genome and find that the concept of what comprises a gene is becoming more and more vague.

This months BioScience journal has an interesting (open-access) article on how the definition of a gene is changing. 

With the discovery that nearly all of the genome is transcribed, the definition of a “gene” needs another revision.

The article describes how the old definitions based around protein function (genes are units of DNA that code for proteins) have had to be expanded with the discovery that a large portion of the genome is transcribed into RNAs that don’t go on to make proteins, but have an important functional role themselves.

Citation:  Hopkins, K (2009). The Evolving Definition of a Gene. BioScience 59(11):928-931. doi: 10.1525/bio.2009.59.11.3