| Full text | |
| Author(s): |
Meyer, Diogo
[1]
;
Aguiar, Vitor R. C.
[1]
;
Bitarello, Barbara D.
[1, 2]
;
Brandt, Debora Y. C.
[1, 3]
;
Nunes, Kelly
[1]
Total Authors: 5
|
| Affiliation: | [1] Univ Sao Paulo, Dept Genet & Evolutionary Biol, BR-05508090 Sao Paulo, SP - Brazil
[2] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, Leipzig - Germany
[3] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 - USA
Total Affiliations: 3
|
| Document type: | Review article |
| Source: | IMMUNOGENETICS; v. 70, n. 1, p. 5-27, JAN 2018. |
| Web of Science Citations: | 24 |
| Abstract | |
Several decades of research have convincingly shown that classical human leukocyte antigen (HLA) loci bear signatures of natural selection. Despite this conclusion, many questions remain regarding the type of selective regime acting on these loci, the time frame at which selection acts, and the functional connections between genetic variability and natural selection. In this review, we argue that genomic datasets, in particular those generated by next-generation sequencing (NGS) at the population scale, are transforming our understanding of HLA evolution. We show that genomewide data can be used to perform robust and powerful tests for selection, capable of identifying both positive and balancing selection at HLA genes. Importantly, these tests have shown that natural selection can be identified at both recent and ancient timescales. We discuss how findings from genomewide association studies impact the evolutionary study of HLA genes, and how genomic data can be used to survey adaptive change involving interaction at multiple loci. We discuss the methodological developments which are necessary to correctly interpret genomic analyses involving the HLA region. These developments include adapting the NGS analysis framework so as to deal with the highly polymorphic HLA data, as well as developing tools and theory to search for signatures of selection, quantify differentiation, and measure admixture within the HLA region. Finally, we show that high throughput analysis of molecular phenotypes for HLA genes-namely transcription levels-is now a feasible approach and can add another dimension to the study of genetic variation. (AU) | |
| FAPESP's process: | 12/18010-0 - Balancing selection in the human genome: detection, causes and consequences |
| Grantee: | Diogo Meyer |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 11/12500-2 - Maladaptation as a byproduct of adaptation: a genomic scale study |
| Grantee: | Bárbara Domingues Bitarello |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 14/12123-2 - Expression and eQTL mapping of HLA genes: analyses based on large-scale RNAseq assays |
| Grantee: | Vitor Rezende da Costa Aguiar |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 12/22796-9 - Population differentiation on genes under strong balancing selection: a case study on the HLA genes |
| Grantee: | Débora Yoshihara Caldeira Brandt |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 12/09950-9 - Evolution of HLA genes: population differentiation and signatures of recent selection in native and admixed populations from Brazil |
| Grantee: | Kelly Nunes |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |