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When they compare the sequenced genomes of two species, say mouse and human, do they compare the entire genomes or just the known coding regions ? Are there sim

When they compare the sequenced genomes of two species, say mouse and human, do they compare the entire genomes or just the known coding regions ? Are there similar regions in mouse and human that we have no clue what they are about ?

08-15 10y ago
What's compared is usually the "homologous regions". That means literally "similar because of common descent", but in practice, it means "similar enough that we think it's homologous". Since parts of genomes can become duplicated, we sometimes have more than one homologous piece in a different species---and then it's typically excluded from the comparison, because we don't know which of the two pieces to compare to. As a practical example, it has been reported that humans and chimpanzees "are 98.6% identical". That's shorthand for "in the detectably homologous parts of their genomes, 98.6% of the nucleotides of chimpanzees and humans are identical". This ignores about 25% of the chimpanzee genome and 20% of the human genome, for which no homologous sequence is known. It also ignores small insertions and deletions, because it's unclear how to define similarity in the presence of those. There are definitely "similar regions" we have no clue about. Comparisons are definitely not restricted to protein coding regions; we typically compare at least whole genes. That includes introns, which sometimes contain regulatory elements, but most of the time nobody knows what, if anything, they do. The same goes for the untranslated regions of genes (5'- and 3'-UTR), which definitely contain regulatory elements, but for the most part aren't understood. And there are probably homologous intergenic regions, too, and we know nothing about their function. I don't remember exact numbers about human-mouse comparisons, but I don't need to to know that we end up comparing incomprehensible stuff: We "understand" 1.5% of the genome---that's the protein coding pieces. That's shallow understanding, but at least something. We could pretend that we also understand any piece of the genome that contains a few scattered regulatory elements. Counting very generously, that might be 15% of the genome. The remainder is completely mysterious. In the human-chimpanzee comparison, ~70% of the genomes are comparable. Clearly, we have no idea what most of that stuff does.

08-15 10y ago

What's compared is usually the "homologous regions". That means literally "similar because of common descent", but in practice, it means "similar enough that we think it's homologous". Since parts of genomes can become duplicated, we sometimes have more than one homologous piece in a different species---and then it's typically excluded from the comparison, because we don't know which of the two pieces to compare to. As a practical example, it has been reported that humans and chimpanzees "are 98.6% identical". That's shorthand for "in the detectably homologous parts of their genomes, 98.6% of the nucleotides of chimpanzees and humans are identical". This ignores about 25% of the chimpanzee genome and 20% of the human genome, for which no homologous sequence is known. It also ignores small insertions and deletions, because it's unclear how to define similarity in the presence of those. There are definitely "similar regions" we have no clue about. Comparisons are definitely not restricted to protein coding regions; we typically compare at least whole genes. That includes introns, which sometimes contain regulatory elements, but most of the time nobody knows what, if anything, they do. The same goes for the untranslated regions of genes (5'- and 3'-UTR), which definitely contain regulatory elements, but for the most part aren't understood. And there are probably homologous intergenic regions, too, and we know nothing about their function. I don't remember exact numbers about human-mouse comparisons, but I don't need to to know that we end up comparing incomprehensible stuff: We "understand" 1.5% of the genome---that's the protein coding pieces. That's shallow understanding, but at least something. We could pretend that we also understand any piece of the genome that contains a few scattered regulatory elements. Counting very generously, that might be 15% of the genome. The remainder is completely mysterious. In the human-chimpanzee comparison, ~70% of the genomes are comparable. Clearly, we have no idea what most of that stuff does.