THE Y CHRO­MO­SOME IS DIS­AP­PEAR­ING – WILL MEN TOO?

Does That Mean Men Will Too?

In Flight Magazine - - IN THIS ISSUE - { TEXT: DAR­REN GRIF­FIN: PRO­FES­SOR OF GE­NET­ICS, UNI­VER­SITY OF KENT & PETER EL­LIS: LEC­TURER IN MOLEC­U­LAR BIOLOGY AND RE­PRO­DUC­TION, UNI­VER­SITY OF KENT / WWW.THE­CON­VER­SA­TION.COM | IMAGES © IS­TOCK­PHOTO.COM }

THE Y CHRO­MO­SOME MAY BE A SYM­BOL OF MAS­CULIN­ITY, BUT IT IS BE­COM­ING IN­CREAS­INGLY CLEAR THAT IT IS ANY­THING BUT STRONG AND EN­DUR­ING. ALTHOUGH IT CAR­RIES THE ‘MAS­TER SWITCH’ GENE, SRY, WHICH DE­TER­MINES WHETHER AN EM­BRYO WILL DE­VELOP AS MALE (XY) OR FE­MALE (XX), IT CON­TAINS VERY FEW OTHER GENES AND IS THE ONLY CHRO­MO­SOME NOT NEC­ES­SARY FOR LIFE. WOMEN, AF­TER ALL, MAN­AGE JUST FINE WITHOUT ONE.

What’s more, theY chro­mo­some has de­gen­er­ated rapidly, leav­ing fe­males with two per­fectly nor­mal X chro­mo­somes, but males with an X and a shriv­elled Y. If the same rate of de­gen­er­a­tion con­tin­ues, the Y chro­mo­some has just 4.6 mil­lion years left be­fore it dis­ap­pears com­pletely.This may sound like a long time, but it isn’t when you con­sider that life has ex­isted on Earth for 3.5 bil­lion years.

A FUN­DA­MEN­TAL FLAW IN DNA

The Y chro­mo­some hasn’t al­ways been like this. If we rewind the clock to 166 mil­lion years ago, to the very first mam­mals, the story was com­pletely dif­fer­ent.The early “proto-Y” chro­mo­some was orig­i­nally the same size as the X chro­mo­some, and con­tained all the same genes. How­ever,Y chro­mo­somes have a fun­da­men­tal

flaw. Un­like all other chro­mo­somes, which we have two copies of in each of our cells,Y chro­mo­somes are only ever present as a sin­gle copy, passed from fa­thers to their sons.

This means that genes on the Y chro­mo­some can­not un­dergo ge­netic re­com­bi­na­tion – the “shuf­fling” of genes that oc­curs in each gen­er­a­tion which helps to elim­i­nate dam­ag­ing gene mu­ta­tions. De­prived of the ben­e­fits of re­com­bi­na­tion, Y chro­mo­so­mal genes de­gen­er­ate over time and are even­tu­ally lost from the genome.

DES­PER­ATE TIMES CALL FOR DES­PER­ATE MEA­SURES

De­spite this, re­cent re­search has shown that the Y chro­mo­some has de­vel­oped some pretty con­vinc­ing mech­a­nisms to “put the brakes on”, slow­ing the rate of gene loss to a pos­si­ble stand­still.

For ex­am­ple, a re­cent Dan­ish study, pub­lished in PLoS Ge­net­ics, se­quenced por­tions of theY chro­mo­some from 62 dif­fer­ent men and found that it is prone to large-scale struc­tural re­arrange­ments al­low­ing “gene am­pli­fi­ca­tion” – the ac­qui­si­tion of mul­ti­ple copies of genes that pro­mote healthy sperm func­tion and mit­i­gate gene loss.

The study also showed that theY chro­mo­some has de­vel­oped un­usual struc­tures called “palin­dromes” – DNA se­quences that read the same for­wards as back­wards – like the word “kayak” – which pro­tect it from fur­ther degra­da­tion.They recorded a high rate of “gene con­ver­sion events” within the palin­dromic se­quences on the Y chro­mo­some – this is ba­si­cally a “copy and paste” process that al­lows dam­aged genes to be re­paired us­ing an un­dam­aged back-up copy as a tem­plate.

Look­ing to other species (Y chro­mo­somes ex­ist in mam­mals and some other species), a grow­ing body of ev­i­dence indicates that Y-chro­mo­some gene am­pli­fi­ca­tion is a gen­eral prin­ci­ple across the board. These am­pli­fied genes play crit­i­cal roles in sperm pro­duc­tion and (at least in ro­dents) in reg­u­lat­ing off­spring sex ra­tio. Writ­ing in the jour­nal Molec­u­lar Biology and Evo­lu­tion re­cently, re­searchers give ev­i­dence that this in­crease in gene copy num­ber in mice is a re­sult of nat­u­ral se­lec­tion.

WILL IT STAY OR WILL IT GO?

On the ques­tion of whether the Y chro­mo­some will ac­tu­ally dis­ap­pear, the sci­en­tific com­mu­nity, like the UK dur­ing the Brexit de­bate, is cur­rently di­vided into the “leavers” and the “re­main­ers”. The lat­ter group ar­gues that its de­fence mech­a­nisms do a great job and have res­cued theY chro­mo­some. But the leavers say that all they are do­ing is al­low­ing the Y chro­mo­some to cling on by its fin­ger­nails, be­fore even­tu­ally drop­ping off the cliff.The de­bate there­fore con­tin­ues.

A lead­ing pro­po­nent of the leave ar­gu­ment, Jenny Graves from La Trobe Uni­ver­sity in Aus­tralia, claims that, if you take a long-term per­spec­tive, the Y chro­mo­somes are in­evitably doomed – even if they some­times hold on a bit longer than ex­pected. In a 2016 paper, she points out that Ja­panese spiny rats and mole voles have lost their Y chro­mo­somes en­tirely, and ar­gues that the pro­cesses of genes be­ing lost or cre­ated on the Y chro­mo­some in­evitably lead to fer­til­ity prob­lems. This in turn can ul­ti­mately drive the for­ma­tion of en­tirely new species.

THE DEMISE OF MEN?

As we ar­gue in a chap­ter in a new e-book (www.springer.com/ us/book/9783319704968), even if the Y chro­mo­some in hu­mans does dis­ap­pear, it does not nec­es­sar­ily mean that males them­selves are on their way out. Even in the species that have ac­tu­ally lost their Y chro­mo­somes com­pletely, males and fe­males are both still nec­es­sary for re­pro­duc­tion.

In these cases, the SRY “mas­ter switch” gene that de­ter­mines ge­netic male­ness has moved to a dif­fer­ent chro­mo­some, mean­ing that these species pro­duce males without need­ing a Y chro­mo­some. How­ever, the new sex-de­ter­min­ing chro­mo­some – the one that SRY moves on to – should then star t the process of de­gen­er­a­tion all over again due to the same lack of re­com­bi­na­tion that doomed their pre­vi­ousY chro­mo­some.

How­ever, the in­ter­est­ing thing about hu­mans is that, while the Y chro­mo­some is needed for nor­mal hu­man re­pro­duc­tion, many of the genes it car­ries are not nec­es­sary if you use as­sisted re­pro­duc­tion tech­niques.This means that ge­netic en­gi­neer­ing may soon be able to re­place the gene func­tion of theY chro­mo­some, al­low­ing same-sex fe­male cou­ples or in­fer­tile men to con­ceive. But even if it be­came pos­si­ble for ev­ery­body to con­ceive in this way, it seems highly un­likely that fer­tile hu­mans would just stop re­pro­duc­ing nat­u­rally.

Although this is an in­ter­est­ing and hotly de­bated area of ge­netic re­search, there is lit­tle need to worry. We don’t even know whether the Y chro­mo­some will dis­ap­pear at all. And, as we’ve shown, even if it does, we will most likely con­tinue to need men so that nor­mal re­pro­duc­tion can con­tinue.

In­deed, the prospect of a “farm an­i­mal”-type sys­tem where a few “lucky” males are se­lected to fa­ther the ma­jor­ity of our chil­dren is cer­tainly not on the hori­zon. In any event, there will be far more press­ing con­cerns over

the next 4.6 mil­lion years.

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