Secuencias conservadas en múltiples especies

Nucleotide sequences that are conserved between many different species are called multi-species conserved sequences. For example, there are thousands of DNA segments between humans, rats, and mice that have remained unchanged since the divergence of these three species from their common mammalian ancestor.  While a small proportion of these conserved sequences encode for RNA or proteins, the majority are non-coding DNA sequences, also called conserved non-genic sequences or CNGs. For example, among the conserved sequences of human and mouse genome, only one-third of them produce a functional transcript while remaining two-thirds are CNGs. CNGs are approximately 50 to 200 nucleotides in length and can be found in intergenic regions in the genome, introns within a gene, or untranslated regions of the RNA transcript.  Some of these sequences are extremely conserved across lineages and are therefore called ultra-conserved sequences. There are more than 5000 ultraconserved sequences between human, rat, and mice genomes, each around 100 bases in length.  Conservation of sequences over millions of years across lineages indicates that multi-species conserved sequences must be critical for survival. However, since most conserved sequences do not code for a protein, their function still remains a mystery. Such conserved sequences are speculated to have the following few functions. First, these sequences may act as enhancers or silencers that bind to the transcription machinery and control the level of gene expression. Second, the conserved sequences may get transcribed into long non-coding RNAs that regulate pre-mRNA maturation and stability.  Third, these sequences might allow functional interaction between chromosomes and help define chromosome territories with distinct gene expression patterns within the nucleus.  Rare mutations in multi-species conserved sequences usually represent a critical step in the evolution of new species. For example, the primate genomes encompass highly conserved specific sequences near the neural development genes. Around 6 million years ago, these conserved sequences underwent nucleotide changes at exceptional rates leading to the evolution of the human lineage.  These regions called Human Accelerated Regions or HARs are involved in critical stages of brain development and improved cognitive functions.