Anthropology.net

We’ve covered the mitochondrial genome of the Denisova individual 2 years ago, back in March 2010. For those not familiar with the Denisova hominin, this specimen represents an archaic human species present at least 41,000 years ago – coexisting with Neandertals and modern humans in the Altai Mountains of Siberia. The species is represented by a tooth and phalange.

A draft of the genome was released shortly afterwards in December, 2010. Today, after 30-fold coverage of the genome using Illumina GAIIx sequencing platform, the complete genome was released. It is free to download and use on Amazon Web Services… weighing in at 160gb.  I can imagine a lot of interesting comparisons can be made with this dataset and am happy the researchers made it available to the public.  There’s a caveat though, you can use the data but however agree that you cannot publish your findings until the researchers at Max Planck first get a stab at it.

If you don’t follow or subscribe to our sister blog Primatology.net, I want to make you aware of an anthropological post I just put up on the newly published orangutan genome. Click here to read about some of the findings, but to wet your appetite, it involves the estimated divergence of the two orangutan species at 400,000 years ago, the relative stabilitiy of their genomes compared to human and chimpanzee, and lastly the shared similarities between human and orang, and not orang and chimp.

Sumatran Orangutan (Pongo abelii)

For quick access to the primary sources, the full citations to the papers discussed are below this read more link.

Read the rest of this entry »

Every time big anthropology news has come out in the last year or so, I’m too busy and drowned under the sea of books and notes for my upcoming exams to immerse myself in it. This happened with Ardipithecus last fall, and now with the draft of the Neandertal genome coming out tomorrow, I can’t help but feel a bit left out. The complete mitochondrial Neandertal genome was released a little under 2 years ago… and now because of high throughput sequencing technology, the draft genome is now complete.

Currently, Science has put up a special section of their website dedicated to this. The news agencies are having issues with embargoes and what not, they put up articles and then take them down. But the word is out, Green and Pääbo’s project to sequence the Neandertal genome is out and there are some interesting findings:

• The comparison of 3 Neandertal samples to 5 modern human genomes showed that Neandertal genome is closer to some populations of modern humans than others
• About 10 loci had distinctly non-African hallmarks
• There’s an attributable 1-4% Neandertal ancestry to non-African modern human populations

There’s a lot more behind this all than I really have time for, unfortunately. So be sure to check out Razib, John Hawks, etc. for all the goodies.

Ari Löytynoja and Nick Goldman have developed a new method that detects and distinguishes insertions and deletions in genomes. Their work was published in the most recent issue of Science. While Löytynoja and Goldman didn’t explicitly write how their new algorithim, described in, “Phylogeny-Aware Gap Placement Prevents Errors in Sequence Alignment and Evolutionary Analysis,” impacts our understanding of human evolution and how we compare primate genomes, it is an important to understand what they’ve accomplished.

Up until now, people compared and contrasted sequencing similarities of multiple genomes using a tool that does a multiple sequence alignment. A commonly used tool is called CLUSTALW. And I’ve used it a lot. CLUSTAL will take long strings of DNA sequences and align them based upon their shared similarities. When a sequence is the same between the samples, they are matched… When sequences aren’t the same, they are marked as gaps. Every consecutive pairwise match between two or more sequences are given a score, and every gap is given a penalty.

Many different alignments are computed and the one with the best score is presented. Phylogenetic trees are drawn off of these sequence alignments. The problem is that this method disregards judging if a length difference between two sequences is a deletion in one or an insertion in the other sequence. This ultimately and systematically creates errors in comparisons of genetic sequences of different species… check it out for yourself, the image below shows the traditional alignment on the left and the new alignment algorithim on the right:

This is where Löytynoja and Goldman’s new algorithm, PRANK, a phylogeny aware algorithm, shines. The phylogeny-aware approach,

“flags the gaps made in previous alignments and, using evolutionary information from related sequences to indicate whether each gap has been created by an insertion or a deletion, permits their “reuse” for inserted characters without further penalty in the next stage of the progressive alignment. In addition, information from closely related sequences can be used to infer sites as “permanent” insertions that cannot be matched in subsequent alignments, so that distinct insertion events are correctly kept separate even when they occur at exactly the same position. If related sequences indicate that a gap is caused by a deletion, flags are removed and no further free gaps at that position are permitted, and the effect is correctly targeted on insertions only.”

Löytynoja explains,

“Say we are comparing the DNA of human and chimp and can’t tell if a deletion or an insertion happened. To solve this our tool automatically invokes information about the corresponding sequences in closely related species, such as gorilla or macaque. If they show the same gap as the chimp, this suggests an insertion in humans.”

In their sample set, they compared sequences of primates to primates, primates to rodents, and primates to all mammals, they were able to identify that insertions are far more common in primate evolution than deletions. Furthermore, the frequency of deletions have been exaggerated because of the inability of previous tools to effectively detect them… which makes me wonder if primates, relatively recent in evolutionary times has been under a relaxed, diversifying level of positively selection? Like some sort of explosion of adaptive radiation of the taxon… I haven’t completely thought this thru, just something that popped into my mind while writing this.

Loytynoja, A., Goldman, N. (2008). Phylogeny-Aware Gap Placement Prevents Errors in Sequence Alignment and Evolutionary Analysis. Science, 320(5883), 1632-1635. DOI: 10.1126/science.1158395

Two similar papers published the latest issues of Nature and Genome Research do high-resolution analyses of the structure of the human genome. They differ in methodology, but have some cool conclusions. The Nature paper, “Mapping and sequencing of structural variation from eight human genomes,” created libraries of 4 African, 2 Asian, and 2 European genomes. From these libraries they created thousands of clones to figure out if there are structural variations in genomes of these eight individuals from diverse geographic ancestry.

The Genome Research paper, “Scanning the human genome at kilobase resolution,” used ditag genome scanning (DGS) to analyze the human genome in high resolution. This method is really similar to serial analysis of gene expression (SAGE), in that genome is fragmented, each tag is ligated with a marker, and a sequencing technique (454 in this particular study) is used ultimately to determine the origin of the fragment in genome. The authors of this paper report that their method was strong enough to provides a kilobase resolution for studying genome structure. DGS is also highly specific and can cover a lot of the genome. Downstream applications of DGS are to validate assembled genomes but also to compare genome similarity and variation in normal populations.

Both methods are able to identify genomic abnormalities like insertions, inversions, deletions, and translocations, much better than current technologies. But why is this all important to anthropology? The Nature paper shows how they were able to find 525 new insertion sequences that are not present in the human reference genome. These new insertion sequences are shown to be variable in copy number between individuals, which ultimately make for 525 new ancestry inherited markers. Furthermore, when the authors of the Nature paper sequenced their clones they were able to find an additional 261 structural variants which reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome.

One last point, most ancestry inherited markers have been SNPs, but more recent research on the human genome has shown, however, that larger-scale differences like the copy number variations (CNVs) and others screened in these two papers, may account for a great deal of genetic variation among individuals.

Got race?

Kidd, J.M., Cooper, G.M., Donahue, W.F., Hayden, H.S., Sampas, N., Graves, T., Hansen, N., Teague, B., Alkan, C., Antonacci, F., Haugen, E., Zerr, T., Yamada, N.A., Tsang, P., Newman, T.L., Tüzün, E., Cheng, Z., Ebling, H.M., Tusneem, N., David, R., Gillett, W., Phelps, K.A., Weaver, M., Saranga, D., Brand, A., Tao, W., Gustafson, E., McKernan, K., Chen, L., Malig, M., Smith, J.D., Korn, J.M., McCarroll, S.A., Altshuler, D.A., Peiffer, D.A., Dorschner, M., Stamatoyannopoulos, J., Schwartz, D., Nickerson, D.A., Mullikin, J.C., Wilson, R.K., Bruhn, L., Olson, M.V., Kaul, R., Smith, D.R., Eichler, E.E. (2008). Mapping and sequencing of structural variation from eight human genomes. Nature, 453(7191), 56-64. DOI: 10.1038/nature06862

Chen, J., Kim, Y.C., Jung, Y., Xuan, Z., Dworkin, G., Zhang, Y., Zhang, M.Q., Wang, S.M. (2008). Scanning the human genome at kilobase resolution. Genome Research DOI: 10.1101/gr.068304.107