Evidence for Variable Selective Pressures at a Large Secondary Structure of the Human Mitochondrial DNA Control Region

• Tipo: Artigo em Revista Científica Internacional
• Data: 2008

Autores

Filipe Pereira (Autor) Outra; Pedro Soares (Autor) Outra; Joao Carneiro (Autor) Outra; Luisa Pereira (Autor) Outra; Martin B Richards (Autor) Outra; David C Samuels (Autor) Outra; Antonio Amorim (Autor) FCUP

Revista

Título: Molecular Biology and Evolution

Vol. 25

Páginas: 2759-2770

ISSN: 0737-4038

Editora: Oxford University Press

Indexação

ISI Web of Knowledge - 42 Citações

ISI Web of Science

Scopus - 43 Citações

Pubmed / Medline

Classificação Científica

FOS: Ciências exactas e naturais > Ciências biológicas

CORDIS: Ciências Naturais

Outras Informações

ID Authenticus: P-003-TPB

DOI: 10.1093/molbev/msn225

Abstract (EN): A combined effect of functional constraints and random mutational events is responsible for the sequence evolution of the human mitochondrial DNA (mtDNA) control region. Most studies targeting this noncoding segment usually focus on its primary sequence information disregarding other informative levels such as secondary or tertiary DNA conformations. In this work, we combined the most recent developments in DNA folding calculations with a phylogenetic comparative approach in order to investigate the formation of intrastrand secondary structures in the human mtDNA control region. Our most striking results are those regarding a new cloverleaf-like secondary structure predicted for a 93-bp stretch of the control region 5'-peripheral domain. Randomized sequences indicated that this structure has a more negative folding energy than the average of random sequences with the same nucleotide composition. In addition, a sliding window scan across the complete mitochondrial genome revealed that it stands out as having one of the highest folding potential. Moreover, we detected several lines of evidence of both negative and positive selection on this structure with high levels of conservation at the structure-relevant stem regions and the occurrence of compensatory base changes in the primate lineage. In the light of previous data, we discuss the possible involvement of this structure in mtDNA replication and/or transcription. We conclude that maintenance of this structure is responsible for the observed heterogeneity in the rate of substitution among sites in part of the human hypervariable region I and that it is a hot spot for the 3' end of human mtDNA deletions.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12