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October 28, 2008

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Neanderthal DNA partially sequenced

Nov. 16, 2006
Courtesy Lawrence Berkeley National Laboratory
and World Science staff

Sci­en­tists have writ­ten out a small frac­tion of the Ne­an­der­thal ge­net­ic code, us­ing it to map out when the stocky hu­man cousins di­verged from our own spe­cies.

The sci­en­tists al­so con­clud­ed that Ne­an­der­thals mat­ed lit­tle if at all with the fore­bears of mod­ern hu­mans—con­tra­dict­ing an­oth­er re­cent study, and adding a new page to a de­bate that has seen flip-flopping con­clu­sions in re­cent years.

A­nal­y­sis of ge­no­mic DNA from fos­sil­ized Ne­an­der­thal bones in­di­cat­ed that Ho­mo sapi­ens and Ho­mo ne­an­derthalen­sis last shared a com­mon an­ces­tor about 700,000 years ago, sci­en­tists say. The two ho­minids split in­to in­to sep­a­rate spe­cies around 400,000 years ago, they add. (Cour­te­sy LBL)

Ne­an­der­thals are the clos­est hom­i­nid rel­a­tives of mod­ern hu­mans. The two spe­cies co-existed in Eu­rope and west­ern Asia as late as 30,000 years ago. 

Sci­en­tists with the U.S. Energy De­part­ment’s Law­rence Ber­k­e­ley Na­tion­al La­b­o­ra­to­ry in Ber­k­e­ley, Ca­lif., and the Joint Ge­nome In­s­ti­tute in Wal­nut Creek, Ca­lif. se­quenced DNA from Ne­an­der­thal fos­sils. 

The re­sults indicate their genomes were at least 99.5-percent iden­ti­cal to ours, the re­search­ers said. Based on these ear­ly find­ings, the spe­cies shared a com­mon an­ces­tor about 700,000 years ago, wrote the in­ves­t­i­ga­tors in the Nov. 17 is­sue of the re­search jour­nal Sci­ence.

Un­til now, knowl­edge of Ne­an­der­thals came from “lim­ited num­ber of bony re­mains and as­so­ci­at­ed ar­ti­facts that are avail­a­ble in hard-to-ac­cess mu­se­um col­lec­tions and field sites,” said Ed­ward Ru­bin, di­rec­tor of the in­sti­tute and of the laboratory’s Ge­nomics Di­vi­sion, and lead au­thor of the stu­dy.

That will change, he added. “In the near fu­ture, an­thro­pol­o­gists will be able to de­vel­op hy­pothe­ses about our ex­tinct an­ces­tors through the scan­ning of bil­lions of base pairs of DNA se­quences avail­a­ble on the web.” A base pair is a “let­ter” of ge­net­ic code.

In 1856, a par­tial hom­i­nid ske­l­e­ton turned up at the Feld­ho­fer Cave in Ger­ma­ny’s Ne­an­der Val­ley. The ske­l­e­ton would be dubbed Ne­an­der­thal Man. It gen­er­at­ed pub­lic cu­ri­os­i­ty and sci­en­tif­ic de­bate that con­tin­ue today. 

Artist's concept of a Neanderthal. (Courtesy Science)

In the late 1990s, sci­en­tists be­gan using ge­net­ic tech­nol­o­gy to study Ne­an­der­thals. Re­search led by Svan­te Pääbo, now of the Max Planck In­sti­tute for Ev­o­lu­tion­ary An­thro­pol­o­gy in Leip­zig, Ger­ma­ny, found that Ne­an­der­thals were cousins rath­er than an­ces­tors of mod­ern hu­mans. 

In the new work, Ru­bin and col­leagues ex­tracted the DNA in the thigh bone of a 38,000-year-old male Ne­an­der­thal from Vin­dija, Cro­a­tia. They re­cov­ered 65,250 base pairs of Ne­an­der­thal DNA, out of a to­tal of an es­t­i­mat­ed three bil­lion base pairs.

Com­par­ing Ne­an­der­thal to hu­man and chim­pan­zee ge­n­omes showed that in ma­ny places the Ne­an­der­thal code matched chimp DNA but not hu­ma­n, Ru­bin said. “This ena­bled us to cal­cu­late for the first time when in pre-history Ho­mo sapi­ens and Ho­mo ne­an­derthalen­sis [Ne­an­der­thals] co­a­lesced to a sin­gle ge­n­ome,” he added.

The analysis found that the com­mon ge­net­ic an­ces­tor of Ne­an­der­thal and mod­ern hu­mans lived about 706,000 years ago, he con­ti­nued. This would be the time when the two line­ages began to diverge, the re­search­ers said; the fi­nal split, though, came some 330,000 years lat­er.

Ru­bin and his col­leagues said they also shed new light on the long-stand­ing ques­tion of wheth­er Ne­an­der­thals and hu­mans mat­ed dur­ing the thou­sands of years the two spe­cies co­hab­i­tated parts of Eu­rope. Some sci­en­tists have sug­gested that rath­er than die out, Ne­an­der­thals as a spe­cies were bred out of ex­ist­ence by the over­whelm­ing pop­u­la­tions of Ho­mo sapi­ens.

Sa­id Ru­bin, “While una­ble to de­fin­i­tive­ly con­clude that in­ter­breed­ing be­tween the two spe­cies of hu­mans did not oc­cur, anal­y­sis... sug­gests the low like­li­hood of it hav­ing oc­curred at any apprecia­ble lev­el.”

Past Ne­an­der­thal gene stud­ies were based on so-called mi­to­chon­dri­al DNA, ge­net­ic ma­te­ri­al that lies out­side the cell nu­cle­us, Ru­bin said. This type tends to stay better-pre­served, he added, but pro­vides lim­it­ed in­for­ma­tion be­cause the vast ma­jor­i­ty of the ge­nome is in the nu­cle­us. His stu­dy fo­cused on this “nu­cl­ear” DNA.

“If you want to un­der­stand how traits like lan­guage and cog­ni­tion are en­cod­ed, you have to study nu­cle­ar DNA,” said James Noo­nan of the Berke­ley Lab and Joint Ge­nome In­sti­tute, a mem­ber of the re­search team.

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Scientists have written out a tiny fraction of the Neanderthal genetic code, using it to map out when the stocky human cousins diverged from our own species. The scientists also concluded that Neanderthals mated little if at all with the forebears of modern humans, contradicting a recent study and adding another page to a debate that has seen flip-flopping conclusions in recent years. Neanderthals are the closest hominid relatives of modern humans. The two species co-existed in Europe and western Asia as late as 30,000 years ago. Scientists with the U.S. Department of Energy’s Lawrence Berkeley National Laboratory and the Joint Genome Institute have sequenced genomic DNA from fossilized Neanderthal bones. Their results show that the genomes of modern humans and Neanderthals are at least 99.5-percent identical, the researchers said. Based on these early results, Homo sapiens and Homo neanderthalensis last shared a common ancestor approximately 700,000 years ago, wrote the researchers in the Nov. 17 issue of the journal Science. Until now, scientists’ knowledge of Neanderthals was drawn from “limited number of bony remains and associated artifacts that are available in hard to access museum collections and field sites,” said Edward Rubin, director of the Joint Genome Institute and of the Berkeley Lab’s Genomics Division, lead author of the study. That will change, he added. “In the near future, anthropologists will be able to develop hypotheses about our extinct ancestors through the scanning of billions of base pairs of DNA sequences available on the web.” A base pair is a “letter” of genetic code. In the summer of 1856, a partial skeleton of a hominid was found at the Feldhofer Cave in the Neander Valley of Germany. This skeleton would eventually be dubbed the “Neanderthal” man and its discovery generated enormous public curiosity and scientific debate that have continued for the past 150 years. Starting around 1997, scientists began applying genetic technology to the study of Neanderthals. Research led by Svante Pääbo, currently of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, established that Neanderthals were cousins rather than ancestors of modern humans. For the results reported in their Science paper, Rubin and Noonan and their colleagues extracted all the DNA in the thigh bone of a 38,000-year-old male Neanderthal from Vindija, Croatia. They recovered 65,250 base pairs of Neanderthal DNA, out of a total of an estimated 3 billion base pairs. Comparing Neanderthal to human and chimpanzee genomes showed that at multiple locations the Neanderthal DNA sequences matched chimpanzee DNA but not human, Rubin said. “This enabled us to calculate for the first time when in pre-history Homo sapiens and Homo neanderthalensis coalesced to a single genome,” Rubin said. Comparative genomics in this study indicated that the common genetic ancestor of Neanderthal and modern humans lived about 706,000 years ago. The ancestors of all humans and Neanderthals split into two separate species some 330,000 years later. Rubin and his colleagues were also able to shed new light on the long-standing question of whether Neanderthals and humans mated during the thousands of years the two species cohabitated parts of Europe. Some scientists have suggested that rather than die out, Neanderthals as a species were bred out of existence by the overwhelming populations of Homo sapiens. Said Rubin, “While unable to definitively conclude that interbreeding between the two species of humans did not occur, analysis of the nuclear DNA from the Neanderthal suggests the low likelihood of it having occurred at any appreciable level.”