Neanderthal and unknown human ancestor DNA found in the "dark heart" of chromosomes

Genes get shuffled and re-dealt with every new generation, meaning many are relatively recent. But while exploring the "dark heart" of the human genome, geneticists have now found some of the most ancient pieces of DNA, inherited from Neanderthals and an as-yet-unknown human relative, which may be affecting our sense of smell to this day.

Although the human genome was fully sequenced in 2003, we still don't understand what everything in there does. One particular dark spot is the centromere – the skinny bit in the middle of the chromosome's X or Y shape – which is full of repeating sequences.

This difficult-to-decipher region could be hiding some of the most ancient sections of human DNA, giving new evolutionary clues to where specific traits came from. That's because the centromere stays more intact through the generations, as opposed to DNA further down the "arms" of the chromosomes which is split and shuffled when forming sperm or eggs.

Researchers from the University of California Davis, the University of California Santa Cruz and Berkeley Lab set out to map the haplotypes – clusters of genes that are usually inherited as a group – located in the centromere. To find out if it was even possible to identify these, they examined the genome of fruit flies, in search of changes to a single DNA letter. Sure enough, they managed to spot these centromeric haplotypes (cenhaps) in fruit fly DNA.

Next, they brought the search over to the human genome, scouring through the 1000 Genomes Project, which is an open database of different genomes designed to showcase human genetic variation. The team examined the centromere sequences in this data, and found haplotypes in the hearts of all the chromosomes on show.

And they uncovered some fascinating clues hiding in there, with some haplotypes dating back half a million years. One of the oldest lineages was found to be absent on the genomes of people descended from a more recent emigration of humans out of Africa.

The centromere of chromosome 11 was particularly interesting. Non-African genomes were found to house very different haplotypes of Neanderthal DNA, which appeared to have diverged as long as a million years ago. And it seems that these Neanderthals are still influencing our senses of smell and taste today – about 34 of our 400 genes related to odorant receptors were found within the chromosome 11 cenhap. Exactly what effects the differences in these genes may have is still unclear, but the link is there.

Perhaps more mysterious is what was found in the centromere of chromosome 12. The team discovered gene sequences that seem to be inherited from even older, more primitive human relatives that remain unknown to science. While we have plenty of evidence of interbreeding between hominin species like modern humans, Neanderthals and Denisovans, there are others that we apparently haven't discovered yet, like the "ghost species" that turned up during studies into human saliva proteins.

Further research will help fill out our understanding of human evolutionary history, as well as diseases like cancer that spring from cell division gone wrong.

The study was published in the journal eLife.

Source: UC Davis