Papers by Tomas MARQUES BONET
Gene, Jan 4, 2005
Evolutionary rates are not uniformly distributed across the genome. Knowledge about the biologica... more Evolutionary rates are not uniformly distributed across the genome. Knowledge about the biological causes of this observation is still incomplete, but its exploration has provided valuable insight into the genomical, historical and demographical variables that influence rates of genetic divergence. Recent studies suggest a possible association between chromosomal rearrangements and regions of greater divergence, but evidence is limited and contradictory. Here, we test the hypothesis of a relationship between chromosomal rearrangements and higher rates of molecular evolution by studying the genomic distribution of divergence between 12,000 human-mouse orthologous genes. Our results clearly show that genes located in genomic regions that have been highly rearranged between the two species present higher rates of synonymous (0.7686 vs. 0.7076) and non-synonymous substitution (0.1014 vs. 0.0871), and that synonymous substitution rates are higher in genes close to the breakpoints of indi...
Bioinformatics (Oxford, England), 2005
Whole genome scans analyze large sets of genetic markers, mainly single nucleotide polymorphisms,... more Whole genome scans analyze large sets of genetic markers, mainly single nucleotide polymorphisms, over the entire genome in order to find variants and regions associated with complex traits so these can be further investigated. Analyzing the results of such scans becomes difficult due to multiple testing problems and to the genomic distributions of recombination, linkage disequilibrium and true associations, which generate an extremely complex network of dependences between markers. Here we present Association Cluster Detector (ACD), a simple tool aiming to ease the analysis of the results of whole genome scans. ACD facilitates correction for multiple tests using several standard procedures and implements a sliding-window heuristic method that helps in detecting potentially interesting candidate regions by exploiting the property of non-random distribution of significantly associated markers. The tool can be downloaded from http://www.upf.es/cexs/recerca/bioevo/softanddata.htm
Nature, Jan 12, 2009
It is generally accepted that the extent of phenotypic change between human and great apes is dis... more It is generally accepted that the extent of phenotypic change between human and great apes is dissonant with the rate of molecular change. Between these two groups, proteins are virtually identical, cytogenetically there are few rearrangements that distinguish ape-human chromosomes, and rates of single-base-pair change and retrotransposon activity have slowed particularly within hominid lineages when compared to rodents or monkeys. Studies of gene family evolution indicate that gene loss and gain are enriched within the primate lineage. Here, we perform a systematic analysis of duplication content of four primate genomes (macaque, orang-utan, chimpanzee and human) in an effort to understand the pattern and rates of genomic duplication during hominid evolution. We find that the ancestral branch leading to human and African great apes shows the most significant increase in duplication activity both in terms of base pairs and in terms of events. This duplication acceleration within the...
Trends in genetics : TIG, 2009
Duplicated sequences are substrates for the emergence of new genes and are an important source of... more Duplicated sequences are substrates for the emergence of new genes and are an important source of genetic instability associated with rare and common diseases. Analyses of primate genomes have shown an increase in the proportion of interspersed segmental duplications (SDs) within the genomes of humans and great apes. This contrasts with other mammalian genomes that seem to have their recently duplicated sequences organized in a tandem configuration. In this review, we focus on the mechanistic origin and impact of this difference with respect to evolution, genetic diversity and primate phenotype. Although many genomes will be sequenced in the future, resolution of this aspect of genomic architecture still requires high quality sequences and detailed analyses.
Genome research, 2011
Structural variation has played an important role in the evolutionary restructuring of human and ... more Structural variation has played an important role in the evolutionary restructuring of human and great ape genomes. Recent analyses have suggested that the genomes of chimpanzee and human have been particularly enriched for this form of genetic variation. Here, we set out to assess the extent of structural variation in the gorilla lineage by generating 10-fold genomic sequence coverage from a western lowland gorilla and integrating these data into a physical and cytogenetic framework of structural variation. We discovered and validated over 7665 structural changes within the gorilla lineage, including sequence resolution of inversions, deletions, duplications, and mobile element insertions. A comparison with human and other ape genomes shows that the gorilla genome has been subjected to the highest rate of segmental duplication. We show that both the gorilla and chimpanzee genomes have experienced independent yet convergent patterns of structural mutation that have not occurred in h...
Annual Review of Genomics and Human Genetics, 2009
We summarize the progress in whole-genome sequencing and analyses of primate genomes. These emerg... more We summarize the progress in whole-genome sequencing and analyses of primate genomes. These emerging genome datasets have broadened our understanding of primate genome evolution revealing unexpected and complex patterns of evolutionary change. This includes the characterization of genome structural variation, episodic changes in the repeat landscape, differences in gene expression, new models regarding speciation, and the ephemeral nature of the recombination landscape. The functional characterization of genomic differences important in primate speciation and adaptation remains a significant challenge. Limited access to biological materials, the lack of detailed phenotypic data and the endangered status of many critical primate species have significantly attenuated research into the genetic basis of primate evolution. Nextgeneration sequencing technologies promise to greatly expand the number of available primate genome sequences; however, such draft genome sequences will likely miss critical genetic differences within complex genomic regions unless dedicated efforts are put forward to understand the full spectrum of genetic variation.
Proceedings of the National Academy of Sciences of the United States of America, Jan 30, 2014
The domestication of the horse ∼5.5 kya and the emergence of mounted riding, chariotry, and caval... more The domestication of the horse ∼5.5 kya and the emergence of mounted riding, chariotry, and cavalry dramatically transformed human civilization. However, the genetics underlying horse domestication are difficult to reconstruct, given the near extinction of wild horses. We therefore sequenced two ancient horse genomes from Taymyr, Russia (at 7.4- and 24.3-fold coverage), both predating the earliest archeological evidence of domestication. We compared these genomes with genomes of domesticated horses and the wild Przewalski's horse and found genetic structure within Eurasia in the Late Pleistocene, with the ancient population contributing significantly to the genetic variation of domesticated breeds. We furthermore identified a conservative set of 125 potential domestication targets using four complementary scans for genes that have undergone positive selection. One group of genes is involved in muscular and limb development, articular junctions, and the cardiac system, and may re...
GigaScience, 2014
Background: Domestic cats enjoy an extensive veterinary medical surveillance which has described ... more Background: Domestic cats enjoy an extensive veterinary medical surveillance which has described nearly 250 genetic diseases analogous to human disorders. Feline infectious agents offer powerful natural models of deadly human diseases, which include feline immunodeficiency virus, feline sarcoma virus and feline leukemia virus. A rich veterinary literature of feline disease pathogenesis and the demonstration of a highly conserved ancestral mammal genome organization make the cat genome annotation a highly informative resource that facilitates multifaceted research endeavors. Findings: Here we report a preliminary annotation of the whole genome sequence of Cinnamon, a domestic cat living in Columbia (MO, USA), bisulfite sequencing of Boris, a male cat from St. Petersburg (Russia), and light 30× sequencing of Sylvester, a European wildcat progenitor of cat domestication. The annotation includes 21,865 protein-coding genes identified by a comparative approach, 217 loci of endogenous retrovirus-like elements, repetitive elements which comprise about 55.7% of the whole genome, 99,494 new SNVs, 8,355 new indels, 743,326 evolutionary constrained elements, and 3,182 microRNA homologues. The methylation sites study shows that 10.5% of cat genome cytosines are methylated. An assisted assembly of a European wildcat, Felis silvestris silvestris, was performed; variants between F. silvestris and F. catus genomes were derived and compared to F. catus. Conclusions: The presented genome annotation extends beyond earlier ones by closing gaps of sequence that were unavoidable with previous low-coverage shotgun genome sequencing. The assembly and its annotation offer an important resource for connecting the rich veterinary and natural history of cats to genome discovery.
Proceedings of the National Academy of Sciences of the United States of America, Jan 2, 2014
Little is known about the genetic changes that distinguish domestic cat populations from their wi... more Little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors. Here we describe a high-quality domestic cat reference genome assembly and comparative inferences made with other cat breeds, wildcats, and other mammals. Based upon these comparisons, we identified positively selected genes enriched for genes involved in lipid metabolism that underpin adaptations to a hypercarnivorous diet. We also found positive selection signals within genes underlying sensory processes, especially those affecting vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff between functional olfactory and vomeronasal receptor gene repertoires in the cat and dog genomes, with an expansion of the feline chemosensory system for detecting pheromones at the expense of odorant detection. Genomic regions harboring signatures of natural selection that distinguish domestic cats from their wild congeners are enriched in neural crest-related...
Genome research, 2013
DNA methylation patterns are important for establishing cell, tissue, and organism phenotypes, bu... more DNA methylation patterns are important for establishing cell, tissue, and organism phenotypes, but little is known about their contribution to natural human variation. To determine their contribution to variability, we have generated genome-scale DNA methylation profiles of three human populations (Caucasian-American, African-American, and Han Chinese-American) and examined the differentially methylated CpG sites. The distinctly methylated genes identified suggest an influence of DNA methylation on phenotype differences, such as susceptibility to certain diseases and pathogens, and response to drugs and environmental agents. DNA methylation differences can be partially traced back to genetic variation, suggesting that differentially methylated CpG sites serve as evolutionarily established mediators between the genetic code and phenotypic variability. Notably, one-third of the DNA methylation differences were not associated with any genetic variation, suggesting that variation in pop...
Science (New York, N.Y.), Jan 7, 2010
Neandertals, the closest evolutionary relatives of present-day humans, lived in large parts of Eu... more Neandertals, the closest evolutionary relatives of present-day humans, lived in large parts of Europe and western Asia before disappearing 30,000 years ago. We present a draft sequence of the Neandertal genome composed of more than 4 billion nucleotides from three individuals. Comparisons of the Neandertal genome to the genomes of five present-day humans from different parts of the world identify a number of genomic regions that may have been affected by positive selection in ancestral modern humans, including genes involved in metabolism and in cognitive and skeletal development. We show that Neandertals shared more genetic variants with present-day humans in Eurasia than with present-day humans in sub-Saharan Africa, suggesting that gene flow from Neandertals into the ancestors of non-Africans occurred before the divergence of Eurasian groups from each other.
Nature, Jan 23, 2010
Using DNA extracted from a finger bone found in Denisova Cave in southern Siberia, we have sequen... more Using DNA extracted from a finger bone found in Denisova Cave in southern Siberia, we have sequenced the genome of an archaic hominin to about 1.9-fold coverage. This individual is from a group that shares a common origin with Neanderthals. This population was not involved in the putative gene flow from Neanderthals into Eurasians; however, the data suggest that it contributed 4-6% of its genetic material to the genomes of present-day Melanesians. We designate this hominin population 'Denisovans' and suggest that it may have been widespread in Asia during the Late Pleistocene epoch. A tooth found in Denisova Cave carries a mitochondrial genome highly similar to that of the finger bone. This tooth shares no derived morphological features with Neanderthals or modern humans, further indicating that Denisovans have an evolutionary history distinct from Neanderthals and modern humans.
Human Molecular Genetics, 2009
The human genome is a highly dynamic structure that shows a wide range of genetic polymorphic var... more The human genome is a highly dynamic structure that shows a wide range of genetic polymorphic variation. Unlike other types of structural variation, little is known about inversion variants within normal individuals because such events are typically balanced and are difficult to detect and analyze by standard molecular approaches. Using sequence-based, cytogenetic and genotyping approaches, we characterized six large inversion
Nature Genetics, 2010
There is a complex relationship between the evolution of segmental duplications and rearrangement... more There is a complex relationship between the evolution of segmental duplications and rearrangements associated with human disease. We performed a detailed analysis of one region on chromosome 16p12.1 associated with neurocognitive disease and identified one of the largest structural inconsistencies in the human reference assembly. Various genomic analyses show that all examined humans are homozygously inverted relative to the reference
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Papers by Tomas MARQUES BONET