Drs David Miller and David Iles from the University of Leeds, in collaboration with Dr Martin Brinkworth at the University of Bradford, have found that sperm writes a DNA signature that can only be recognised by an egg from the same species. This enables fertilisation and may even explain how a species develops its own unique genetic identity.
Dr Iles says, "What we have discovered is a previously unrecognised DNA packaging 'signature' in mammalian sperm that may be essential for successful fertilisation of the egg and development of the embryo. We think it may also be ancient in origin."
Without the right 'key', successful fertilisation either cannot occur, or if it does, development will not proceed normally. Notably, disturbances in human sperm DNA packaging are known to cause male infertility and pregnancy failures.
This 'lock and key' mechanism has other profound implications. Not only does it explain why some otherwise healthy men produce sperm that is sterile, but it also explains how different species evolve and retain their own identity.
Says Dr Miller, "Up until now, Doctors have struggled to understand idiopathic male infertility. Our latest research offers a plausible explanation for why some sperm malfunction or fail to function correctly."
If the DNA carried by a sperm cell was unwound and stretched out, it would actually measure more than a metre in length. In order to fit all this DNA into the microscopic space within the head of the sperm cell, the DNA needs to be very tightly coiled, or packaged. The Leeds study showed that in human and mouse sperm, not all of the DNA is packaged in the same way. Whilst most of the paternal DNA is compressed in an extremely compact fashion, some is packaged less tightly.
"There is a definite pattern to the way DNA is packaged in sperm cells and we can see that this pattern is the same in unrelated fertile men. It is different in the sperm of infertile men. This implies that there is a significance to the packaging of DNA that has a direct relevance to male fertility," says Dr Iles.
Detailed analyses of the DNA in the 'open', less tightly packaged conformation, showed this DNA carries much of the information critical for activating genes essential for directing the development of the embryo. Further investigations showed the same conformation to exist in the sperm of several unrelated human donors and remarkably, highly similar packaging patterns to exist in the sperm of mice.
DNA regions in the 'open' conformation may therefore be more vulnerable to damaging toxins, such as those in cigarette smoke and certain anti-cancer drugs, than those that are tightly packaged. As Dr Brinkworth says, "this might mean that anything capable of causing genetic damage to sperm could have particular significance for the development of the embryo".
The findings also help explain why inter-species breeding is so rarely successful.
Where the locks and keys of two species do not match, however similar their DNA is, no viable offspring can be born. Occasionally, for example, with horses and donkeys, offspring are produced - but because the sperm and egg signatures are incompatible, their development as embryos is abnormal and any offspring are almost always infertile.
The research team believes that the same mechanism must also have played a role during human evolution. In the ancient history of mankind, Neanderthals co-existed with modern humans over many thousands of years. Sexual encounters between these two closely related species cannot be ruled out, yet there is no evidence in our DNA of a legacy from such couplings. It is possible that if offspring were produced, they either did not survive long or if they did, they were unable to breed.
Darren Tomlinson, Michelle Peckham, Megan Wright, BBSRC (Jun 2018), £150,443
Simon Walker, Royal Society (Jun 2018), £337,601
Tom Thirkell, N8 Agrifood (Jun 2018), £14,870
Stephen Muench with Glaxo SmithKline & UCB Celltech, BBSRC Industrial Partnership Award (Apr 2018), £480,225
Steve Clapcote, BBSRC (Apr 2018), £443,072
Helen Miller, Innovate UK (Apr 2018), £999,960
Elisabetta Groppelli, David Rowlands & Stanley Lemon (University of North Carolina), Medical Research Foundation Fellowship (Apr 2018), £293,494
Nikesh Patel, Medical Research Foundation fellowship (Apr 2018), £290,976
Graham Askew with colleagues in Hull and Liverpool, BBSRC (Apr 2018), £150,498
Andrew Macdonald, Neil Ranson & Richard Foster, Kidney Research UK (Apr 2018), £82,821
Jessica Kwok & Ralf Richter, Leverhulme Trust (Apr 2018), £298,273
Julie Aspden, Royal Society (Apr 2018), £20,000
Liz Duncan, Royal Society (Mar 2018), £14,602
Alex O'Neill & Ryan Seipke, BBSRC (Feb 2018), £45,489
Jim Deuchars, Royal Society (Feb 2018), £16,300
Stefan Kepinski & Netta Cohen, Leverhulme Trust (Feb 2018), £320,387
Lisa Collins, BBSRC (Feb 2018), £49,950
Alison Baker, BBSRC (Feb 2018), £30,000
Lars Jeuken, BBSRC (Feb 2018), £30,000
Nikita Gamper, BBSRC (Feb 2018), £30,000
Scott Bowen, Leducq Foundation Grant (Feb 2018), £28,470
Jessica Kwok and Ronaldo Ichiyama, International Spinal Research Trust (Feb 2018), £94,450
Alex O'Neill, Oxford Drug Design (Jan 2018), £86,098
Dave Lewis and Colleagues in South Africa, HEFCE Global Challenge Research (Jan 2018), £48,000
Sarah Calaghan, Ed White, John Colyer, Isuru Jayasinghe, BHF (Jan 2018), £128,308
Christine Foyer and Alison Baker, HEFCE GCRF Grant (Jan 2018), £71,158
Alison Baker, Yun Yung Gong and Lindsay Stringer and ICRISAT India, HEFCE GCRF Grant (Jan 2018), £27,000
Graham Askew, Simon Walker, BBSRC (Jan 2018), £699,781
Jennifer Tomlinson, Royal Society (Jan 2018), £512,801
Alison Dunn, NERC (Dec 2017), £18,000
Jennifer Tomlinson, Royal Society-Research Fellows Enhancement Award (Dec 2017), £94,681
Helen Miller, AB AGri Grant (Dec 2017), £73,600
Simon Walker, Royal Society Enhancement Award (Dec 2017), £10,000
Carrie Ferguson, Bryan Taylor, Harry Rossiter, The Physiological Society (Dec 2017), £7,392
Ralf Richter, Royal Society (Dec 2017), £6,000
Christine Foyer, British Council Newton Fund (Dec 2017), £49,840
Adrian Whitehouse and colleagues in School of Chemistry and University of Liverpool, MRC (Nov 2017), £622,319
Michelle Peckham, Neil Ransom, MRC (Nov 2017), £495,159
Dave Lewis, British Council India (Nov 2017), £22,540
Hannah Dugdale, Royal Society (Nov 2017), £15,000
Elton Zeqiraj, Royal Society (Nov 2017), £15,000
Shaunna Burke, Cancer Research UK Innovation Grant (Nov 2017), £20,000
Alex O'Neill and colleagues in Chemistry, BBSRC (Nov 2017), £431,865
Jessica Kwok, Wings for Life (Nov 2017), £87,365
Tom Bennett, BBSRC (Oct 2017), £523,679
Neil Ranson, Darren Tomlinson, BBSRC (Oct 2017), £494,318
Nikita Gamper, BBSRC (Oct 2017), £490,426
Amanda Bretman and colleagues from UEA, NERC (Oct 2017), £430,886
Juan Fontana, Rosetrees Trust consumables grant (Oct 2017), £22,500
Helen Miller, DSM Nutritional Products AG (Sep 2017), £69,988
Neil Ranson, Juan Fontana, Mark Harris, Michelle Peckham, Ralf Richter, Peter Stockley, Patricija Van Oosten-Hawle and colleagues in Engineering, FMH and MAPS, Wellcome Trust Equipment Call (Sep 2017), £418,000
Jamie Johnston, Physiological Society (Sep 2017), £10,000
Frank Sobott, Adrian Goldman, Mark Harris, Andrew Macdonald, Stephen Muench, Sheena Radford and colleagues in FMH and MAPS, Wellcome Trust Equipment Call (Aug 2017), £415,000