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“Junk DNA” key to human evolution?

Sept. 4, 2008
Courtesy Yale University
and World Science staff

Of the three bil­lion ge­net­ic let­ters that spell the hu­man ge­nome, sci­en­tists have iden­ti­fied a hand­ful that they say may have con­tri­but­ed to the ev­o­lu­tion­ary changes that en­abled peo­ple to use tools and walk up­right.

Of the three bil­lion ge­net­ic let­ters that spell the hu­man ge­nome, sci­en­tists have iden­ti­fied a hand­ful that they say may have con­tri­but­ed to the ev­o­lu­tion­ary changes that en­abled peo­ple to use tools and walk up­right. (Art­work cour­tesy NA­SA)


The find­ings sug­gest our ev­o­lu­tion may have been driv­en not only by changes in genes, but in ar­eas of the ge­nome once thought of as “junk DNA,” the re­search­ers said. 

The re­sults come from a com­par­a­tive anal­y­sis of the hu­man, chim­pan­zee, rhe­sus ma­caque and oth­er ge­nomes re­ported in the Sept. 5 issue of the re­search jour­nal Sci­ence.  The scientists noted al­tera­t­ions in this DNA that ac­ti­vat­ed genes in pri­mor­di­al thumb and big toe in a mouse em­bryo. 

“Our study iden­ti­fies a po­ten­tial ge­net­ic con­trib­u­tor to fun­da­men­tal mor­pho­log­i­cal [struc­tur­al] dif­fer­ences be­tween hu­mans and apes,” said Yale Uni­ver­s­ity ge­net­icist James Noo­nan,  the sen­ior au­thor.

Re­search­ers have long sus­pected changes in gene ac­tiva­t­ion con­tri­but­ed to hu­man ev­o­lu­tion. But this was long dif­fi­cult to study be­cause the ge­net­ic se­quences that con­trol this ac­tiva­t­ion were mostly un­iden­ti­fied. 

In re­cent years, sci­en­tists have found many of these con­trol re­gions lie with­in so-called “junk DNA”—gene se­quences whose func­tion had been un­clear be­cause they don’t di­rectly code for the pro­duc­tion of mo­le­cules, as oth­er DNA does. Re­search­ers dis­cov­ered that these non-coding re­gions, far from be­ing junk, con­tain thou­sands of bits of code that serve as ge­net­ic switches to turn oth­er genes on or off.

Underlining their im­por­tance, many of these non-coding se­quences have re­mained si­m­i­lar even across dis­tantly re­lat­ed ver­te­brate spe­cies. Re­cent stud­ies al­so sug­gest some of these “con­served non-coding se­quences” con­trol the genes for hu­man de­vel­op­ment. Noo­nand and col­la­bo­ra­tors searched the vast non-coding re­gions of the hu­man ge­nome to iden­ti­fy gene se­quences of this type whose func­tion may have changed dur­ing the ev­o­lu­tion of hu­mans from our ape-like an­ces­tors.

The re­search­ers looked for se­quences with more “let­ters,” or base pairs, in hu­mans than in oth­er pri­ma­tes. The fastest-evolving se­quence they iden­ti­fied, termed HAC­NS1, is highly con­served but was found to have ac­cu­mu­lat­ed changes in 16 base pairs, or “letters,” since hu­mans and chim­pan­zees branched apart some six mil­lion years ago. This was es­pe­cially sur­pris­ing, as the hu­man and chim­pan­zee ge­nomes are ex­tremely si­m­i­lar over­all, Noo­nan said.

Us­ing mouse em­bry­os, Noo­nan and his col­la­bo­ra­tors ex­am­ined how HAC­NS1 and re­lat­ed se­quences in chim­pan­zee and rhe­sus mon­key gov­erned gene ac­tiva­t­ion dur­ing de­vel­op­ment. The hu­man se­quence ac­ti­vat­ed genes in the de­vel­op­ing mouse limbs, in con­trast to the chim­pan­zee and rhe­sus se­quences. 

Most in­tri­guing, the hu­man se­quence drove gene act­i­vation at the base of the pri­mor­di­al thumb in the fore­limb and the great toe in the hind limb, they found. The re­sults pro­vid­ed tan­ta­liz­ing, but re­search­ers say pre­lim­i­nary, ev­i­dence that the changes may have con­tri­but­ed to adapta­t­ions in the hu­man an­kle, foot, thumb and wrist—ad­van­tages that un­der­lie our ev­o­lu­tion­ary suc­cess.

How­ev­er, Noo­nan stressed that it is still un­known wheth­er HAC­NS1 causes changes in gene ex­pres­sion in hu­man limb de­vel­op­ment or wheth­er HAC­NS1 would cre­ate hu­man-like limb de­vel­op­ment if in­tro­duced di­rectly in­to the ge­nome of a mouse. “The long-term goal is to find many se­quences like this and use the mouse to mod­el their ef­fects on the ev­o­lu­tion of hu­man de­vel­op­ment,” Noo­nan said.


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Of the three billion genetic letters that spell the human genome, scientists have identified a handful that they say may have contributed to the evolutionary changes that enabled people to use tools and walk upright. The findings suggest our evolution may have been driven not only by changes in genes, but in areas of the genome once thought of as “junk DNA,” the researchers said. The results come from a comparative analysis of the human, chimpanzee, rhesus macaque and other genomes reported in the research journal Science. The researchers said they identified alterations in this DNA that activated genes in primordial thumb and big toe in a developing mouse embryo. “Our study identifies a potential genetic contributor to fundamental morphological differences [differences in form] between humans and apes,” said Yale University geneticist James Noonan, senior author of the study. Researchers have long suspected changes in gene activation contributed to human evolution. But this was long difficult to study because the genetic sequences that control this activation were mostly unidentified. In recent years, scientists have found many of these control regions lie within so-called “junk DNA”—gene sequences whose function had been unclear because they don’t directly code for the production of molecules, as other DNA does. Researchers discovered that these non-coding regions, far from being junk, contain thousands of sequences that act as genetic switches to turn other genes on or off. As an indication of their biological importance, many of these non-coding sequences have remained similar even across distantly related vertebrate species. Recent studies also suggest some of these “conserved non-coding sequences” control the genes for human development. Noonand and collaborators searched the vast non-coding regions of the human genome to identify gene regulatory sequences whose function may have changed during the evolution of humans from our ape-like ancestors. The researchers looked for sequences with more “letters,” or base pairs, in humans than in other primates. The fastest-evolving sequence they identified, termed HACNS1, is highly conserved among vertebrate species but has accumulated variations in 16 base pairs since the divergence of humans and chimpanzees some six million years ago. This was especially surprising, as the human and chimpanzee genomes are extremely similar overall, Noonan said. Using mouse embryos, Noonan and his collaborators examined how HACNS1 and related sequences in chimpanzee and rhesus monkey governed gene activation during development. The human sequence activated genes in the developing mouse limbs, in contrast to the chimpanzee and rhesus sequences. Most intriguing for human evolution, the human sequence drove expression at the base of the primordial thumb in the forelimb and the great toe in the hind limb, they found. The results provided tantalizing, but researchers say preliminary, evidence that the changes may have contributed to adaptations in the human ankle, foot, thumb and wrist—advantages that underlie our evolutionary success. However, Noonan stressed that it is still unknown whether HACNS1 causes changes in gene expression in human limb development or whether HACNS1 would create human-like limb development if introduced directly into the genome of a mouse. “The long-term goal is to find many sequences like this and use the mouse to model their effects on the evolution of human development,” Noonan said.