IDCHPRIMATESDS · Identification and characterization of primate-specific duplications and an assessment of intra-specific patterns of selection and copy-number variation

Periodic Report Summary - IDCHPRIMATESDS (Identification and characterization of primate-specific duplications and an assessment of intra-specific patterns of selection and copy-number variation)

Primate genomes have been found enriched for complex patterns of interspersed segmental duplications. These regions differ in structure and content between closely related primates, so the main goal of this proposal was to characterise the evolution of segmental duplications in the human genome. The proposal had three specific aims: a) Discovery of segmental duplications in non-human primate genomes. b) Assess the level of polymorphism of segmental duplications within species. c) Understand the evolutionary origin and selection on these regions. The main work as a postdoc, took two years of hard job and the coordination of many efforts. The human genome has an unusual pattern of segmental duplications, with many implications to genomic disease. This was the first work to study where this pattern comes from and revealed some unexpected properties regarding the evolution of human segmental duplications. This paper was published in Nature last year being me the first author. The fellowship was properly acknowledged in the paper. I have also been co-author in six other collaborative papers in journals such as Nature Genetics, PLoS Genetics, and Genome Research with contributions estimating of copy number in paralogous regions of the human genome, creating the first copy number variable regions (CNVs) map in chimpanzees or studying the fascinating evolution of IRGM in great apes. I am also part of five Genome Consortia (Neanderthal, Bonobo, Gorilla, Orangutan and Marmoset), being the team leader in the section of duplications and structural variation in four of them. Several high profile papers are being submitted and will be generated in the near future by these Consortia. Finally, I have published two review papers in Trends in Genetics and Annual Review of Human Genetics and Genomics as first author. In total, my Marie Curie International Outgoing Fellowship has been acknowledged in 11 papers in 2 years in journals such as Nature, Nature genetics, Genome Research, Plos Genetics and Trends in Genetics. Several results, specifically linked to the proposal, have been achieved. First and from a scientific point of view, we have shown that most human segmental duplications arose during a narrow window of evolution (7-10 million years ago) within the ancestral lineage of humans and great apes-a timepoint when most other mutational processes were slowing down. This is highly relevant to understand the evolution of our genome and that's the main reason why the paper was accepted in Nature. As a result, we have provided at: http://humanparalogy.gs.washington.edu/primates2009/burst.htm the first validated set of primate segmental references, which is widely used as a reference for any duplication analyses in primates. Second, and as a part of the main paper, I have addressed the question on how polymorphic these regions are within primates. We provided of the first measures trying to establish how different these regions behave compare to other forms of mutations and we found that similarly to single nucleotide polymorphisms, humans are less polymorphic, even for these regions compared to the other great-apes. And finally, my student and I are finishing together a paper on a new method on estimating the strength of natural selection on duplicated gene families. The implication of this research was broad from some basic aspect of evolutionary biology to the fine scale resolution of many loci implicated in genomic disease. The best view of the impact of my research is given by the fact that I was awarded an ERC starting grant for this year to start my own lab in Barcelona.

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