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Three articles published on 11 November in Nature present important advances in understanding the evolution of birds and mammals, made possible by new methods for comparing the genomes of hundreds of species.
Comparative genomics uses genomic data to study evolutionary relationships between species and to identify DNA sequences with essential functions preserved in many species. This approach requires aligning the genome sequences so that corresponding locations in different genomes can be compared, but this becomes increasingly difficult as the number of genomes grows.
Researchers from the UC Santa Cruz Genomics Institute developed a powerful new genome alignment method that made new studies possible, including the largest ever genomic alignment of more than 600 vertebrate genomes. The findings provide a detailed insight into how species relate to each other on a genetic level.
“We are literally lining up the DNA sequences to see the corresponding positions in each genome, so that we can look at the individual elements of the genome and see in detail what has changed and what has remained unchanged over evolutionary time,” explained Benedict Paten, professor associate of biomolecular engineering at UC Santa Cruz and corresponding author of two of the new articles.
Identifying the DNA sequences that are preserved, remaining unchanged over millions of years of evolution, allows scientists to identify elements of the genome that control important functions in a wide range of species. “It tells you that something is important there – it hasn’t changed because it can’t – and now we can see it in higher resolution than ever,” Paten explained.
The previous generation of alignment tools relied on comparing everything to a single reference genome, resulting in a problem called “reference bias”. Paten and co-author Glenn Hickey originally developed a non-referencing alignment program called Cactus, which was state-of-the-art at the time, but only worked on a small scale. UCSC graduate student Joel Armstrong (now at Google) then extended it to create a powerful new program called Progressive Cactus, which can work for hundreds and even thousands of genomes.
“Most of the previous alignment methods were limited by the reference bias, so if human is the reference, they could tell you a lot about the relationship of the human genome to the mouse genome and a lot about the relationship of the human genome to the dog genome, but not much about the relationship of the mouse genome to the dog genome, “Armstrong explained. “What we’ve done with Progressive Cactus is figure out how to avoid limiting reference bias while remaining efficient and accurate enough to handle the massive scale of today’s genome sequencing projects.”
Armstrong is the lead author of all three articles and the first author of the article describing Progressive Cactus and presenting the results of an alignment of 605 genomes representing hundreds of millions of years of vertebrate evolution. This unprecedented alignment combines two smaller alignments, one for 242 placental mammals and another for 363 birds. The other two articles focus separately on mammalian and bird genome alignments.
This international collaborative effort was coordinated by an organizational group led by co-authors Guojie Zhang at the University of Copenhagen and China National GeneBank, Elinor Karlsson at the Broad Institute of Harvard and MIT, and Paten at UCSC. The genomic data used in these analyzes were generated by two large consortia: the 10,000 Bird Genomes (B10K) project for avian genomes and the Zoonomy project for mammalian genomes.
For years, scientists have been making plans to sequence and analyze the genomes of tens of thousands of animals. Co-author David Haussler, director of the UCSC Genomics Institute, helped kickstart the Genome 10K project in 2009. Related efforts include the Vertebrate Genome Project and the Earth BioGenome Project, and all of these projects are now catching on.
“These are very forward-looking documents, because the methods we have developed will scale for alignments of thousands of genomes,” Paten said. “As sequencing technology becomes cheaper and faster, people are sequencing hundreds of new species, and this opens up new possibilities for understanding the evolutionary relationships and genetic basis of biology. There is a colossal amount of information in these genomes. “.
Source of the story:
Materials provided by University of California – Santa Cruz. Original written by Tim Stephens. Note: The content can be changed by style and length.
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