Comparative genomics is a powerful means for understanding the relationships among genome sequence, structure, and function. Comparisons among the genomes of different species have provided insights into the plasticity of genomes, have contributed to our understanding of the relationship between genomic structure and function, and have helped to elucidate functional elements of the genome. Studies of chromosomal organization and gene order have contributed to our understanding of gene silencing and functional gene clustering, studies of highly conserved genomic elements have led to the identification of regulatory regions and highlighted functional constraints, and studies of genomic regions that have diverged rapidly or maintained large amounts of variation provide insight into the evolution and biology of specific traits.
Comparative genome sequencing
Initially, comparative studies focused on individual genes or loci to understand specific regions, genomic features, and traits. Advances in genomic sequencing have enabled comparisons between whole genomes of species with reference or lower-quality assemblies. Until recently, these studies relied largely on whole-genome sequence data from a few species, primarily those used as model organisms for biomedical research. Improved technology and reduced costs now allow investigators to sequence multiple species chosen to address specific comparative genomics questions. For example, comparisons among multiple distantly-related species can shed light on the evolutionary origins of proteins; comparisons among species within one phylum (e.g., vertebrates) can reveal constrained gene regulatory regions; comparisons among still more closely-related species can reveal rapidly changing genomic regions associated with changes in morphology or other phenotypes. Comparisons of species at different phylogenetic distances can reveal the genomic underpinnings of convergent phenotypes (e.g., loss of limbs in snakes and whales; advent of multicellularity in independent eukaryotic lineages). Comparative genomic analysis can provide information about the genomic basis for evolutionary novelties and elucidate the biology of genomes in addition to resolving species relationships and informing conservation biology. For each of these, the possibility of obtaining data from multiple species enabled the community to address new questions through the development and application of new approaches and analytic methods for comparative genomics.
Although recent advances in technology have enabled more genomes to be sequenced, many of those studies have been motivated by questions that are not primarily related to comparative genomics. For example, many organisms have been sequenced because they are used in specific areas of biomedical research or agriculture.
This funding opportunity focuses on the development of approaches and methods that will increase capacity to use primary data from multiple species to address specific biological questions or sets of related questions; while primary data may be generated and used to answer specific biological questions under this funding opportunity, these should be used as proof of principle for generalizable strategies, methods, and resources that are more widely applicable.
Moving beyond comparative genome sequence
This FOAFOA is not limited to studies of genomic sequence data. Comparisons between organisms at the level of gene regulation or genome organization may also inform many of the general questions above. Therefore, applications that propose to develop approaches that use transcriptomic, epigenomic, gene regulatory network, or other sequence-based, genome-wide functional data types will also be considered.
Awards under this FOAFOA will support development of new comparative genomics research approaches using genomic data types to understands biological systems, networks, and pathways. High priority will be given to applications that propose innovative and promising approaches to genome-wide and multi-species comparisons at the DNA, RNA, regulatory element, pathway, or similar genomic levels; that enable answering novel questions or that significantly improve the state-of-the-art; that integrate genomics and other data types across a diversity of species; that develop new computational methods, tools, and algorithms for using comparative genomics approaches to study biological processes; that fully leverage multiple data types and functional information available from diverse species; or that provide comprehensive comparative genomics resources and tools for the community. Studies of a single species or a small number of species are not encouraged, and will only be considered when the data would address a biologically important gap in knowledge and if this data would, when compared with data from other species, contribute to an understanding of unique genomic features, organizations, or functional mechanisms. Since a major goal of this FOA is to provide access to genomic resources by the research community, awardees will be required to actively disseminate the data and resources supported under these awards.
NHGRI is interested in supporting development of comparative genomics methods and resources with strong justification of biological relevance, particularly relevance to human health and disease, that will enable areas of research including, but not limited to:
- Genome structure and organization across multiple species, particularly in lineages with diverse or unusual genomic architectures
- The relationship between genomic structure and function, especially in non-coding regions of the genome
- Evolutionary patterns and processes across multiple species including but not limited to divergent and convergent patterns of gene modification, gene regulation (including splicing), regulatory element activity, and regulatory networks
- Better understanding of the relationship between changes in DNA sequence, transcriptomic and epigenomic signatures, and phenotype/fitness, given that they do not always have simple correlations;
- The genetic underpinnings and evolution of health-related function in multiple species;
- The comparative population genomics of highly variable regions in multiple species;
- Integration of the genomes from ancient DNA and extant species to elucidate the genetic bases and evolutionary forces underlying speciation, adaptation to diverse environments, and the connections among genes, environments, and phenotypic form and function.
Deadlines: standard dates apply
Filed Under: Funding Opportunities