The interplay between DNA methylation and sequence divergence in recent human evolution.

نویسندگان

  • Irene Hernando-Herraez
  • Holger Heyn
  • Marcos Fernandez-Callejo
  • Enrique Vidal
  • Hugo Fernandez-Bellon
  • Javier Prado-Martinez
  • Andrew J Sharp
  • Manel Esteller
  • Tomas Marques-Bonet
چکیده

Despite the increasing knowledge about DNA methylation, the understanding of human epigenome evolution is in its infancy. Using whole genome bisulfite sequencing we identified hundreds of differentially methylated regions (DMRs) in humans compared to non-human primates and estimated that ∼25% of these regions were detectable throughout several human tissues. Human DMRs were enriched for specific histone modifications and the majority were located distal to transcription start sites, highlighting the importance of regions outside the direct regulatory context. We also found a significant excess of endogenous retrovirus elements in human-specific hypomethylated.We reported for the first time a close interplay between inter-species genetic and epigenetic variation in regions of incomplete lineage sorting, transcription factor binding sites and human differentially hypermethylated regions. Specifically, we observed an excess of human-specific substitutions in transcription factor binding sites located within human DMRs, suggesting that alteration of regulatory motifs underlies some human-specific methylation patterns. We also found that the acquisition of DNA hypermethylation in the human lineage is frequently coupled with a rapid evolution at nucleotide level in the neighborhood of these CpG sites. Taken together, our results reveal new insights into the mechanistic basis of human-specific DNA methylation patterns and the interpretation of inter-species non-coding variation.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Sequence-Level Mechanisms of Human Epigenome Evolution

DNA methylation and chromatin states play key roles in development and disease. However, the extent of recent evolutionary divergence in the human epigenome and the influential factors that have shaped it are poorly understood. To determine the links between genome sequence and human epigenome evolution, we examined the divergence of DNA methylation and chromatin states following segmental dupl...

متن کامل

An Evolutionary and Phylogenetic Study of the BMP15 Gene

DNA sequence data contains a wealth of biologically useful information. Recent innovations in DNA sequencing technology have greatly increased our capacity to determine massive amounts of nucleotide sequences. These sequences can be used to specify the characteristics of different regions, interpret the evolutionary relationships between categorized groups, likelihood of performing multiple com...

متن کامل

Epigenetics and evolution.

Epigenetic mechanisms traditionally have been studied in the domains of development and disease, but they may also play important roles in ecological and evolutionary processes. In this article, we revisit historical as well as recent studies that indicate significant impacts of epigenetic processes on evolution. Our main focus is DNA methylation, which is a prevalent chemical modification of g...

متن کامل

DNA methylation and evolution of duplicate genes.

The evolutionary mechanisms underlying duplicate gene maintenance and divergence remain highly debated. Epigenetic modifications, such as DNA methylation, may contribute to duplicate gene evolution by facilitating tissue-specific regulation. However, the role of epigenetic divergence on duplicate gene evolution remains little understood. Here we show, using comprehensive data across 10 diverse ...

متن کامل

Analyses of methylation status of CpG islands in promoters of miR-9 genes family in human gastric adenocarcinoma

In the recent years deregulation for microRNAs expression pattern have emerged as a possible molecular factor for carcinogenesis. It has been reported that the expression of miR-9 was down-regulated in human gastric adenocarcinoma. To figure out the molecular mechanism of this down regulation, the methylation status in promoters of miR-9 family loci were compared in the human gastric adenocarci...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Nucleic acids research

دوره 43 17  شماره 

صفحات  -

تاریخ انتشار 2015