Maladaptation as a byproduct of adaptation: a genomic scale study

• Grant number: 11/12500-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2011
• End date: April 30, 2016
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Diogo Meyer
• Grantee: Bárbara Domingues Bitarello
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 12/19563-2 - Detecting genes and genomic regions under balancing selection in the human genome, BE.EP.DR

Abstract

Recent genome scans based on a comparison of non-synonymous and synonymous substitution rates (dN/dS) as well as studies comparing polymorphism and divergence, allow the understanding of the impact of selection throughout the genome. It became clear then that positive selection was common in the human lineage, for coding and noncoding regions. Selection does not act independently on linked loci: its efficiency is directly related to the rate of recombination. Slightly deleterious mutations, when genetically linked to advantageous variants, will be likely to stay longer than expected under the neutral model. In some organisms, there is evidence that genes subject to purifying selection are mainly concentrated in regions of low recombination and that the selective pressure on coding regions interferes with the efficiency of selection in adjacent regions. Since positive selection events were common in our lineage and selection on a gene or region of the genome has the potential to affect adjacent regions, our prediction is that genes selected regions within or close to selected genes will have increased rates of maladaptive evolution. In this project we tested this prediction. Our strategy is to define classes of events with high probability to be deleterious. These include mutations that result in suboptimal synonymous codons and loss of function mutations in transcription or splicing regulatory elements. Having defined which mutations are deleterious, we will then compare their rates of substitution between selected and non-selected loci selected, or between loci that are linked to selected loci and loci that are not. We will make these comparisons using McDonald-Kreitman-like tests, which allow comparisons of polymorphism and divergence. We will use polymorphism data from the 1000 genomes project and divergence data from humans and other mammals. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MEYER, DIOGO; AGUIAR, VITOR R. C.; BITARELLO, BARBARA D.; BRANDT, DEBORA Y. C.; NUNES, KELLY. A genomic perspective on HLA evolution. IMMUNOGENETICS, v. 70, n. 1, p. 5-27, JAN 2018. (12/18010-0, 11/12500-2, 14/12123-2, 12/22796-9, 12/09950-9)

BITARELLO, BARBARA D.; DE FILIPPO, CESARE; TEIXEIRA, JOAO C.; SCHMIDT, JOSHUA M.; KLEINERT, PHILIP; MEYER, DIOGO; ANDRES, AIDA M.. Signatures of Long-Term Balancing Selection in Human Genomes. GENOME BIOLOGY AND EVOLUTION, v. 10, n. 3, p. 939-955, MAR 2018. (11/12500-2, 12/19563-2, 12/18010-0)

LE DUC, DIANA; RENAUD, GABRIEL; KRISHNAN, ARUNKUMAR; ALMEN, MARKUS SALLMAN; HUYNEN, LEON; PROHASKA, SONJA J.; ONGYERTH, MATTHIAS; BITARELLO, BARBARA D.; SCHIOTH, HELGI B.; HOFREITER, MICHAEL; et al. Kiwi genome provides insights into evolution of a nocturnal lifestyle. GENOME BIOLOGY, v. 16, p. 15-pg., 2015-07-23. (11/12500-2)

LE DUC, DIANA; RENAUD, GABRIEL; KRISHNAN, ARUNKUMAR; ALMEN, MARKUS SALLMAN; HUYNEN, LEON; PROHASKA, SONJA J.; ONGYERTH, MATTHIAS; BITARELLO, BARBARA D.; SCHIOTH, HELGI B.; HOFREITER, MICHAEL; et al. Kiwi genome provides insights into evolution of a nocturnal lifestyle. Genome Biology, v. 16, JUL 23 2015. (11/12500-2)

BITARELLO, BARBARA DOMINGUES; FRANCISCO, RODRIGO DOS SANTOS; MEYER, DIOGO. Heterogeneity of Ratios at the Classical HLA Class I Genes over Divergence Time and Across the Allelic Phylogeny. Journal of Molecular Evolution, v. 82, n. 1, p. 38-50, JAN 2016. (11/12500-2, 09/09127-8)

BRANDT, DEBORA Y. C.; AGUIAR, VITOR R. C.; BITARELLO, BARBARA D.; NUNES, KELLY; GOUDET, JEROME; MEYER, DIOGO. Mapping Bias Overestimates Reference Allele Frequencies at the HLA Genes in the 1000 Genomes Project Phase I Data. G3-GENES, GENOMES, GENETICS, v. 5, n. 5, p. 931-941, MAY 1 2015. (12/18010-0, 11/12500-2, 13/12162-5, 14/12123-2, 12/22796-9, 12/09950-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BITARELLO, Bárbara Domingues. Balancing selection in the human genome: biological relevance and deleterious consequence. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) São Paulo.