Sykes published the first report on retrieving DNA from ancient bone (Nature, 1989). Sykes has been involved in a number of high-profile cases dealing with ancient DNA, including that of Cheddar Man. However, the Cheddar Man findings have been disputed and it has been suggested that the results were the consequence of contamination with modern DNA. His work also suggested a Florida accountant by the name of Tom Robinson was a direct descendant of Genghis Khan, a claim that was subsequently disproved.
Sykes is best known outside the community of geneticists for his bestselling books on the investigation of human history and prehistory through studies of mitochondrial DNA. He is also the founder of Oxford Ancestors, a genealogical DNA testing firm.
The Seven Daughters of Eve and Blood of the Isles
In 2002 Sykes published a book for the popular audience, The Seven Daughters of Eve, in which he explained how the dynamics of maternal mitochondrial DNA (mtDNA) inheritance leave their mark on the human population in the form of genetic clans sharing common maternal descent. He notes that the majority of Europeans can be classified in seven such clans, known scientifically as haplogroups, distinguishable by differences in their mtDNA that are unique to each group, with each clan descending from a separate prehistoric female-line ancestor. He referred to these seven 'clan mothers' as 'daughters of Eve', a reference to the mitochondrial Eve to whom the mtDNA of all modern humans traces. Based on the geographical and ethological distribution of the modern descendants of each clan he assigned provisional homelands for the seven clan mothers, and used the degree to which each clan diverges to approximate the time period when the clan mother would have lived. He then uses these deductions to give 'biographies' for each of the clan mothers, assigning them arbitrary names based on the scientific designation of their haplogroup (for example, using the name Xenia for the founder of haplogroup X).
In his 2006 book Blood of the Isles (published in the United States and Canada as Saxons, Vikings and Celts: The Genetic Roots of Britain and Ireland), Sykes examines British genetic "clans". He presents evidence from mitochondrial DNA, inherited by both sexes from their mothers, and the Y chromosome, inherited by men from their fathers, for the following points:
- The genetic makeup of Britain and Ireland is overwhelmingly what it has been since the Neolithic period and to a very considerable extent since the Mesolithic period, especially in the female line, i.e. those people, who in time would become identified as British Celts (culturally speaking), but who (genetically speaking) should more properly be called Cro-Magnon. In continental Europe, this same Cro-Magnon genetic legacy gave rise to the Basques. "Basque" and "Celt" are cultural designations, not genetic ones.
- The contribution of the Celts of Central Europe to the genetic makeup of Britain and Ireland was minimal; most of the genetic contribution to the British Isles of those we think of as Celtic, came from western continental Europe, i.e. the Atlantic seaboard.
- The Picts were not a separate people: the genetic makeup of the formerly Pictish areas of Scotland shows no significant differences from the general profile of the rest of Britain. The two "Pictland" regions are Tayside and Grampian.
- The Anglo-Saxons are supposed, by some, to have made a substantial contribution to the genetic makeup of England, but in Sykes's opinion it was under 20 percent of the total, even in Southern England.
- The Vikings (Danes and Norwegians) also made a substantial contribution, which is concentrated in central, northern and eastern England - the territories of the ancient Danelaw. There is a very heavy Viking contribution in the Orkney and Shetland Islands, in the vicinity of 40 percent. Women as well as men contributed substantially in all these areas, showing that the Vikings engaged in large-scale settlement.
- The Norman contribution was extremely small, on the order of 2 percent.
- There are only sparse traces of the Roman occupation, almost all in Southern England.
- In spite of all these later contributions, the genetic makeup of the British Isles remains overwhelmingly what it was in the Neolithic: a mixture of the first Mesolithic inhabitants with Neolithic settlers who came by sea from Iberia and ultimately from the eastern Mediterranean.
- There is a difference between the genetic histories of men and women in Britain and Ireland. The matrilineages show a mixture of original Mesolithic inhabitants and later Neolithic arrivals from Iberia, whereas the patrilineages are much more strongly correlated with Iberia. This suggests (though Sykes does not emphasize this point) replacement of much of the original male population by new arrivals with a more powerful social organization.
- There is evidence for a "Genghis Khan effect", whereby some male lineages in ancient times were much more successful than others in leaving large numbers of descendants; e.g. Niall of the Nine Hostages in 4th and 5th century Ireland and Somerled in 12th century Scotland.
Some quotations from the book follow. (Note that Sykes uses the terms "Celts" and "Picts" to designate the pre-Roman inhabitants of the Isles who spoke Celtic and does not mean the people known as Celts in central Europe.)
|“||[T]he presence of large numbers of Jasmine’s Oceanic clan … says to me that there was a very large-scale movement along the Atlantic seaboard north from Iberia, beginning as far back as the early Neolithic and perhaps even before that. The mere presence of Oceanic Jasmines indicates that this was most definitely a family based settlement rather that the sort of male-led invasions of later millennia.||”|
|“||The Celts of Ireland and the Western Isles are not, as far as I can see from the genetic evidence, related to the Celts who spread south and east to Italy, Greece and Turkey from the heartlands of Hallstadt and La Tene...during the first millennium BC…The genetic evidence shows that a large proportion of Irish Celts, on both the male and female side, did arrive from Iberia at or about the same time as farming reached the Isles. (…)
The connection to Spain is also there in the myth of Brutus. This too may be the faint echo of the same origin myth as the Milesian Irish and the connection to Iberia is almost as strong in the British regions as it is in Ireland. (…)
|“||Here again, the strongest signal is a Celtic one, in the form of the clan of Oisin, which dominates the scene all over the Isles. The predominance in every part of the Isles of the Atlantis chromosome (the most frequent in the Oisin clan), with its strong affinities to Iberia, along with other matches and the evidence from the maternal side convinces me that it is from this direction that we must look for the origin of Oisin and the great majority of our Y-chromosomes…I can find no evidence at all of a large-scale arrival from the heartland of the Celts of central Europe amongst the paternic genetic ancestry of the Isles… can||”|
His theories regarding the origins of the British has been largely invalidated, Basque like Neolithic farmers did populate Britain (and all of Northern Europe) during the Neolithic period, though over 90% of their DNA was overturned by a North European Bell Beaker population of ultimate Russian Steppe origin as part of an ongoing migration process that brought large amounts of Steppe DNA (including the R1b haplogroup) to North and West Europe.  Modern autosomal genetic clustering is testament to this fact, as both modern and Iron age British and Irish samples cluster genetically very closely with other North European populations, not Iberians, Galicians, Basques or those from the south of France. 
Alleged hominid samples
Dr. Bryan Sykes and his team at Oxford University carried out DNA analysis of presumed Yeti samples and thinks the samples may have come from a hybrid species of bear produced from a mating between a brown bear and a polar bear. Sykes told BBC News:
|“||I think this bear, which nobody has seen alive, may still be there and may have quite a lot of polar bear in it. It may be some sort of hybrid and if its behaviour is different from normal bears, which is what eyewitnesses report, then I think that may well be the source of the mystery and the source of the legend.||”|
|— Dr. Bryan Sykes, BBC News (17 October 2013)|
He conducted another similar survey in 2014, this time examining samples attributed not just to yeti but also to Bigfoot and other "anomalous primates." The study concluded that two of the 30 samples tested most closely resembled the genome of a palaeolithic polar bear, and that the other 28 were from living mammals.
The samples were subsequently re-analysed by Ceiridwen Edwards and Ross Barnett. They concluded that the mutation that had led to the match with a polar bear was a damage artefact, and suggested that the two hair samples were in fact from Himalayan brown bears (U. arctos isabellinus). These bears are known in Nepal as Dzu-the (a Nepalese term meaning cattle-bear), and have been associated with the myth of the yeti. Sykes and Melton acknowledged that their GenBank search was in error and but suggested that the hairs were instead a match to a modern polar bear specimen "from the Diomede Islands in the Bering Sea reported in the same paper”. They maintained that they did not see any sign of damage in their sequences and commented that they had “no reason to doubt the accuracy of these two sequences any more than the other 28 presented in the paper”. Multiple further analyses, including replication of the single analysis conducted by Sykes and his team, were carried out in a study conducted by Eliécer E. Gutiérrez, a researcher at the Smithsonian Institution and Ronald H. Pine, affiliated at the University of Kansas. All of these analyses found that the relevant genetic variation in brown bears makes it impossible to assign, with certainty, the Himalayan samples to either that species or to the polar bear. Because brown bears occur in the Himalayas, Gutiérrez and Pine stated that there is no reason to believe that the samples in question came from anything other than ordinary Himalayan brown bears 
- Sykes, Bryan (1999), The Human Inheritance: Genes, Language, and Evolution, Oxford University Press, ISBN 978-0-19-850274-6
- —— (2002), The Seven Daughters of Eve, Corgi, ISBN 978-0-552-14876-4 (see The Seven Daughters of Eve)
- —— (2003), Adam's Curse: A Future Without Men, Bantam, ISBN 978-0-593-05004-0 (see Adam's Curse)
- —— (2006), Blood of the Isles: Exploring the Genetic Roots of Our Tribal History, Bantam, ISBN 978-0-593-05652-3
- —— (2011), DNA USA: A Genetic Biography of America, W. W. Norton & Company, ISBN 978-0-393-07804-6
- —— (2015), The Nature of the Beast, Hodder & Stoughton, ISBN 978-1-444-79126-6
- —— (2019), Once a Wolf: The Science Behind Our Dogs' Astonishing Genetic Evolution, Liveright, ISBN 978-1-63149-379-9
- Leake, J. Scientist savaged for bigfoot claim Sunday Times, 29 March 2015.
- Debrett's People of Today Debrett's People of Today. Accessed 2 February 2016.
- Bandelt, Hans-Jürgen; Yao, Yong-Gang; Richards, Martin B.; Salas, Antonio (2008). "The brave new era of human genetic testing". BioEssays. 30 (11–12): 1246–1251. doi:10.1002/bies.20837. PMID 18937378.
- Tom Robinson (16 June 2006), Genghis Khan or Not? That is the Question (Internet Archive version)., Self published, archived from the original on 2006-12-13, retrieved 31 January 2013
- Matching Genghis Khan, familytreedna.com, archived from the original on 8 March 2009, retrieved 3 June 2008
- Henderson, Mark (30 May 2006), How I am related to Genghis Khan, London: The Times, retrieved 2010-04-27
- Nicholas Wade. Falling from Genghis's family tree New York Times, 21 June 2006. Accessed 31 January 2013.
- Sykes 2006, pp. 280–281
- Sykes 2006, pp. 281–282
- Sykes 2006, pp. 283–284
- Japanese women seek their ancestral roots in Oxford Archived October 3, 2006, at the Wayback Machine by Tessa Holland, 25 June 2006, Kyodo News
- Olalde, I; et al. (May 2017). "The Beaker Phenomenon and the Genomic Transformation of Northwest Europe". bioRxiv 135962.
- Novembre, J; et al. (November 2008), "Genes mirror geography within Europe", Nature, 456 (7218): 98–101, Bibcode:2008Natur.456...98N, doi:10.1038/nature07331, PMC 2735096, PMID 18758442
- Lao O, Lu TT, Nothnagel M, et al. (August 2008), "Correlation between genetic and geographic structure in Europe", Curr. Biol., 18 (16): 1241–8, doi:10.1016/j.cub.2008.07.049, PMID 18691889
- Staff (17 October 2013). "British scientist 'solves' mystery of Himalayan yetis". BBC News. Retrieved 22 October 2013.
- Lawless, Jill (17 October 2013). "DNA Links Mysterious Yeti To Ancient Polar Bear". Associated Press. Archived from the original on 23 October 2013. Retrieved 22 October 2013.
- Sykes, B. C.; Mullis, R. A.; Hagenmuller, C.; Melton, T. W.; Sartori, M. (2 July 2014). "Genetic analysis of hair samples attributed to yeti, bigfoot and other anomalous primates". Proceedings of the Royal Society B: Biological Sciences. 281 (1789): 20140161. doi:10.1098/rspb.2014.0161. PMC 4455819. PMID 25994680.
- Edwards, CJ; Barnett, R (2015). "Himalayan 'yeti' DNA: polar bear or DNA degradation? A comment on 'Genetic analysis of hair samples attributed to yeti' by Sykes et al. (2014)". Proc. R. Soc. B. 282 (1800): 20141712. doi:10.1098/rspb.2014.1712. PMC 4298200. PMID 25520353.
- McKenzie S. Scientists challenge "abominable snowman" DNA results. BBC News Highlands and Islands, 17 December 2014.
- Melton, TW; Sartori, M; Sykes, BC (2015). "Response to Edward and Barnett". Proc. R. Soc. B. 282 (1800): 20142434. doi:10.1098/rspb.2014.2434. PMC 4298211. PMID 25520360.
- Gutiérrez, Eliécer E.; Pine, Ronald H. (2015). "No need to replace an "anomalous" primate (Primates) with an "anomalous" bear (Carnivora, Ursidae)". ZooKeys (487): 141–154. doi:10.3897/zookeys.487.9176. PMC 4366689. PMID 25829853.